As funes do licopeno do tomate e seu

papel na sade humana

Autores: Joseph Levy, PhD e Yoav Sharoni, PhD
Fonte: HerbalGram. 2004;62:49-56
Aeri!an "o#ani!a$ %o&n!i$
Introduo
%aro#en'i(es, !opos#os en!on#ra(os e )r&#as e ve*e#ais,
+ene)i!ia a sa,(e h&ana por (esepenhar & ipor#an#e pape$
no )&n!ionaen#o !e$&$ar. A ipor#-n!ia (o !aro#en'i(e +e#a-
!aro#eno na (ie#a, o pre!&rsor (a vi#aina A, #e si(o re!onhe!i(a
por &i#as (.!a(as. /ais re!en#een#e, o $i!openo, !aro#en'i(e
vere$ho en!on#ra(o pre(oinan#een#e e #oa#es e e a$*&ns
)r&#os e ve*e#ais, #e (esper#a(o s&+s#an!ia$ in#eresse en#re
pes0&isa(ores (a 1rea .(i!a. A!re(i#a-se 0&e o $i!openo po(e ser
+en.)i!o e pa#o$o*ias !oo !-n!er e (oen2a !oronariana, +e
!oo e o&#ras !on(i23es !r4ni!as. 5ssas a$e*a23es #6 si(o
es#&(a(as e7#ensivaen#e, e es#&(os epi(eio$'*i!os,
inves#i*a23es +io0&8i!as (as proprie(a(es (o $i!openo e a#rav.s
(a ava$ia29o (a +io(isponi+i$i(a(e (o $i!openo e (ie#as +asea(as
e #oa#es. 5s#e ar#i*o res&e o es#a(o a#&a$ (o !onhe!ien#o
(as proprie(a(es (o $i!openo, se& po#en!ia$ pape$ na sa,(e
h&ana e 1reas para )&#&ras pes0&isas !o es#a s&+s#-n!ia.
Funes do licopeno no organismo humano
Apesar (e n9o ser !onsi(era(o & n&#rien#e essen!ia$, pes0&isas
#6 (eons#ra(o 0&e o $i!openo po(e #ra:er (iversos +ene)8!ios
para a sa,(e h&ana. Sen(o o prin!ipa$ !aro#en'i(e no san*&e
h&ano, o $i!openo pro#e*e os $ip8(eos, pro#e8nas e D;A (o (ano
o7i(a#ivo. Por ser & po#en#e se0<es#ra(or (o o7i*6nio =sin*$e#=
>&a )ora rea#iva (e o7i*6nio?, #&(o in(i!a 0&e #e proprie(a(es
an#io7i(an#es !opara#ivaen#e ais po#en#es 0&e a aior par#e
(os o&#ros !aro#en'i(es p$as1#i!os
@
.
A $i!openo #e si(o !onsi(era(o & e)i!a: e espe!8)i!o ini+i(or (a
pro$i)era29o (e !.$&$as !an!er8*enas,
2, B
0&e . re*&$a(a por &
e$a+ora(o pro!esso !haa(o =!i!$o !e$&$ar=. A (ivis9o !e$&$ar r1pi(a
e (es!on#ro$a(a . !ara!#er8s#i!a (o e#a+o$iso (e !.$&$as
!an!er8*enas; a !apa!i(a(e (o $i!openo (e re#ar(ar a pro*ress9o
(o !i!$o !e$&$ar po(e e7p$i!ar s&a !ope#6n!ia e re#ar(ar a
evo$&29o (e !er#os #ipos (e !-n!er. $i!openo po(e prevenir a
#rans)ora29o a$i*na >o pro!esso !e$&$ar envo$vi(o !o a
#rans)ora29o (e &a !.$&$a nora$ e !an!er8*ena?. A ini+i29o (e
!on#a#o . & (os e!anisos 0&e !on#ro$a a (ivis9o !e$&$ar
e7!essiva. Por es#e e!aniso, &a !.$&$a, n& a+ien#e
pop&$oso, in#erroper1 s&a &$#ip$i!a29o. 5s#r&#&ras espe!iais na
e+rana !e$&$ar, (enoina(as =*ap-C&n!#ion=, )&n!iona !oo
!anais (e !o&ni!a29o en#re as !.$&$as. %.$&$as norais s9o
#a+. ini+i(as por !on#a#o e poss&e =*ap-C&n!#ions= )&n!ionais,
en0&an#o 0&e a aioria (as !.$&$as #&orais e7i+e po&!as (essas
es#r&#&ras. 5s#a esp.!ie (e !aro#en'i(e ain(a in(&: a )ora29o (a
pro#e8na !one7ina 4B, & (os prin!ipais !oponen#es (esses
!anais, e, por#an#o, res#a&ra as =*ap C&n!#ions=
4
. Da+. a#&a
so+re en:ias (a Ease FF, 0&e a&7i$ia na e$iina29o (e
!ar!in'*enos e #o7inas (o or*aniso. A o(i)i!a29o nos n8veis (e
#an#as pro#e8nas re*&$a#'rias es#1 re$a!iona(a !o a !apa!i(a(e (o
$i!openo (e o(&$ar v1rios )a#ores (e #rans!ri29o 0&e s9o a#ores
!have no pro!esso (e s8n#ese (e novas pro#e8nas !e$&$ares.
5, 6
Estrutura, absoro e transporte
Li!openo . (e)ini(o 0&ii!aen#e !oo & !aro#eno a!8!$i!o !o
@@ (&p$as $i*a23es !onC&*a(as, nora$en#e, #o(as na
!on)i*&ra29o =#rans= >Ei*. @?. As $i*a23es (&p$as es#9o s&Cei#as a
isoeri:a29o e v1rios is4eros na !on)i*&ra29o =!is=
>prin!ipa$en#e 5, 9, @B, o& @5? s9o en!on#ra(os e p$an#as e
#a+. no p$asa. Des(e 0&e o or*aniso h&ano . in!apa: (e
sin#e#i:ar !aro#en'i(es a par#ir (e pre!&rsores pro(&:i(os
en(o*enaen#e, a!a+a sen(o #o#a$en#e (epen(en#e (as )on#es
(ie#.#i!as >e7'*enas? (e !aro#en'i(es. De )ora *era$, #oa#e e
se&s pro(&#os a$ien#8!ios (eriva(os !on#ri+&e !o pe$o enos
G5H (o $i!openo provenien#e (a (ie#a e h&anos. As res#an#es
@5H s9o nora$en#e o+#i(os (o e$9o, =*rape)r&i#=, *oia+a e
a9o I #o(os es#es )r&#os s9o )on#es (ie#.#i!as (e $i!openo,
por. e n8veis &i#o in)eriores ao #oa#e. >Da+e$a @?.
Da+e$a @: %on#e,(o (e $i!openo (e a$ien#os !o&ns
ipo de alimento
!uant" em mg
por #$$ gr"
%efer&ncias
Joia+a Eres!a, vere$ha 5.4 K
Doa#e Eres!o, vere$ho B.@-K.K G
S&!o (e Doa#e K.GB G
Pas#a (e Doa#e B0.0K G G
Jrape)r&i# Eres!o, vere$ho B.B6 G
/e$9o Eres!o, vere$ho 4.@ K
Le#!h&p @6.6 K
/o$ho (e Pi::a B2.9 G
/o$ho (e 5spa*&e#e @K.5 9
Papaia Eres!o, vere$ho 2.0-5.B @0
S&!o (e #oa#e, sopa (e #oa#e, Me#!h&p, o$ho (e pi::a e (e
espa*&e#e s9o a aioria (os pro(&#os respons1veis pe$a in!$&s9o
(o $i!openo na (ie#a. A apor#e (os !aro#en'ri(es na esa #e
si(o es#&(a(o por &i#os anos. A +io(isponi+i$i(a(e na (ie#a (o
$i!openo pare!e (epen(er (e (iversos )a#ores. N ais +e
a+sorvi(o (e a$ien#os !o:i(os e ri!os e $ip8(eos.
@@
Oa ve:
in*eri(o, o $i!openo apare!e no p$asa. Fni!ia$en#e nos
0&i$oi!rons >i!ros!'pi!as par#8!&$as *or(&rosas e&$si)i!a(as
en!on#ra(as no soro e na $in)a e res&$#a(o (a (i*es#9o (as
*or(&ras? e nas )ra23es PLDL >very $oQ-(ensi#y $ipopro#ein? e,
#ar(iaen#e, nas LDL >$oQ-(ensi#y $ipopro#eins, #a+. !haa(as
=a&= !o$es#ero$? e nas RDL >hi*h-(ensi#y $ipopro#eins, nora$en#e
!haa(as =+o= !o$es#ero$?. As ais a$#os n8veis s9o en!on#ra(os
nas LDL. As !on!en#ra23es s.ri!as varia si*ni)i!a#ivaen#e en#re
!er!a (e 20 e 500 !*S$i#ro (e soro !o *ran(es varia23es
in#erpessoais.
Diversas $inhas (e evi(6n!ia s&*ere 0&e as LDL o7i(a(as s9o
(anosas T pare(e ar#eria$, e 0&e a a#eros!$erose po(e ser a#en&a(a
por an#io7i(an#es na#&rais. %oo repor#a(o por E&hran e# a$., o
$i!openo (o #oa#e, iso$a(o o& !o+ina(o !o o&#ros an#io7i(an#es
na#&rais, ini+e a o7i(a29o (as LDL
@2
. A(i!iona$en#e, o eso
*r&po repor#o& 0&e a s&p$een#a29o (ie#.#i!a !o $i!openo (o
#oa#e >60 *S(ia?, 0&an(o a(inis#ra(a e seis hoens por &
per8o(o (e #r6s eses, res&$#o& n&a si*ni)i!an#e re(&29o nos se&s
n8veis p$as1#i!os (e !o$es#ero$ LDL. 5sses (a(os es#9o e a!or(o
!o os res&$#a(os in vitro 0&e (eons#ra 0&e o $i!openo s&prie
a s8n#ese (o !o$es#ero$ e a&en#a a a#ivi(a(e (os re!ep#ores (e
LDL nos a!r')a*os.
@B
A $i!openo . en!on#ra(o na aioria (os #e!i(os h&anos, as n9o
se a!&&$a &ni)oreen#e.
@4
R1 &a !on!en#ra29o pre)eren!ia$ (e
$i!openo espe!ia$en#e nas a(renais e #es#8!&$os. A !oprova(a
!apa!i(a(e (e e$evar os n8veis (e $i!openo nos #e!i(os !ons#i#&i &
pr.-re0&isi#o para &#i$i:1-$o !oo s&p$een#o (ie#.#i!o para
e$horar a sa,(e. 5n#re#an#o, )oi re!en#een#e repor#a(o 0&e a
s&p$een#a29o (e $i!openo (a '$eo-resina (o #oa#e e vo$&n#1rios
s&+e#i(os a !ir&r*ias e$e#ivas pro(&:i& & si*ni)i!a#ivo a&en#o
nos !aro#en'i(es no p$asa, pe$e e #e!i(o a(iposo.
@5
Po&!o se
!onhe!e a !er!a (o e#a+o$iso e (e*ra(a29o (o $i!openo e
a8)eros. Diversos e#a+'$i#os o7i*ena(os #6 si(o en!on#ra(os
no p$asa e #e!i(os, as o&#ros es#&(os s9o ne!ess1rios no
sen#i(o (e ava$iar s&as a#ivi(a(es )isio$'*i!as, se . 0&e es#as
e7is#e.
Pes0&isas !$8ni!as (eons#rara 0&e o $i!openo . a+sorvi(o ais
rapi(aen#e a par#ir (e pro(&#os (e #oa#es pro!essa(os a 0&en#e
(o 0&e (os n9o !o:i(os e 0&e a a+sor29o . a&en#a(a pe$a
presen2a (e '$eo.
@6
'enef(cios do licopeno relacionados ao sinergismo
com outros micronutrientes
Uevisan(o os (a(os re$a!iona(os a 0&iiopreven29o (e v1rias
pa#o$o*ias, )i!a evi(en#e 0&e a &#i$i:a29o (e & ,ni!o !aro#en'i(e,
o& 0&a$0&er o&#ro i!ron&#rien#e 0&e #e se os#ra(o e)i!a: e
o(e$os in vitro e aniais, n9o #6 si(o !oprova(os e es#&(os
e h&anos. Fs#o ., n9o h1 =+a$a= 1*i!a. De )a#o, evi(6n!ias
a!&&$a(as s&*ere 0&e &a or0&es#ra(a e sin.r*i!a a29o (e
v1rios i!ron&#rien#es pare!e ser a +ase para a a#ivi(a(e preven#iva
(e &a (ie#a ri!a e ve*e#ais e )r&#as. 5n#re#an#o, as )on#es (e
$i!openo &#i$i:a(as na aioria (os es#&(os e h&anos a0&i
revisa(os )ora (e pro(&#os (e #oa#e pro!essa(os o& e7#ra#os (e
#oa#e !on#en(o $i!openo e o&#ros i!ron&#rien#es (o #oa#e e
!aro#en'i(es e (iversas propor23es. A $i!openo p&ro n9o )oi
#es#a(o !oo a*en#e iso$a(o e es#&(os (e preven29o e
h&anos. Por o&#ro $a(o, &i#os es#&(os 0&e (eons#ra o e)ei#o
+en.)i!o (o $i!openo e a$iviar !on(i23es !r4ni!as )ora
!on(&:i(os e in(iv8(&os 0&e re!e+era a$ien#os (eriva(os (o
#oa#e, o& e7#ra#os (e #oa#e, as n9o !o a s&+s#-n!ia iso$a(a.
Por e7ep$o, a prepara29o (e '$eo-resina &#i$i:a(a e &i#os
es#&(os #a+. !on#inha o&#ros !aro#en'i(es (o #oa#e !oo o
)i#oeno, )i#o)$&eno e +e#a-!aro#eno >Ei*&ra @?. Oa !r8#i!a revis9o
(es#es es#&(os po(e 0&es#ionar se o&#ros !opos#os a$. (o
$i!openo no #oa#e po(e ser respons1veis pe$o e)ei#o +en.)i!o;
en#re#an#o, es#&(os in vitro s&por#a a a29o sin.r*i!a (os
!aro#en'i(es e o&#ros an#io7i(an#es presen#es no #oa#e.
@K-@9
5s#e !onhe!ien#o )oi #es#a(o e es#&(o re!en#e
20
0&e !oparo&
a e)i!1!ia (e #oa#es se!os e !on*e$a(os >p' (e #oa#e o&
$i!openo p&ro e o(e$os (e !-n!er (e pr's#a#a e ra#os?. As
ra#os )ora #ra#a(os !o o !ar!ino*6ni!o ;/O >;-e#i$-;-
ni#roso&r.ia? !o+ina(o !o an(ro*6nios para es#i&$ar a
!ar!ino*6nese pros#1#i!a. A !apa!i(a(e (es#as (&as prepara23es,
0&e !on#. $i!openo, (e a&en#ar a so+revi(a )ora !opara(as.
A or#a$i(a(e por !-n!er (e pr's#a#a )oi in)erior e 25H >P V 0.09?
para ra#os a$ien#a(os !o o p' (e #oa#e, !opara#ivaen#e aos
ra#os a$ien#a(os !o (ie#a !on#ro$e. A or#a$i(a(e por !-n!er (e
pr's#a#a (e ra#os a$ien#a(os !o $i!openo p&ro )oi sii$ar ao *r&po
!on#ro$e. As a&#ores !on!$&8ra 0&e o !ons&o (e p' (e #oa#e,
as n9o o $i!openo p&ro, ini+i& a !ar!ino*6nese pros#1#i!a,
s&*erin(o 0&e pro(&#os (e #oa#e !on#en(o o&#ros !opos#os,
asso!ia(os ao $i!openo, a o(i)i!ara. ;& e(i#oria$ para$e$o,
Jann e# a$.
2@
, assina$o&-se 0&e es#e es#&(o !on#ri+&i para o (e+a#e
a!er!a (a preven29o (o !-n!er. /ais espe!i)i!aen#e, se e$a .
ais +e s&!e(i(a !o a$ien#os in#e*rais o& !o !opos#os
iso$a(os. 5$es os#ra 0&e !aro#en'i(es e o&#ros !opos#os
se!&n(1rios (e p$an#as es#9o envo$vi(os e a23es (e !opos#os
in#era#ivos, &a !op$e7i(a(e 0&e $ii#a a &#i$i:a29o (e a+or(a*ens
re(&!ionis#as 0&e, por s&a ve:, pro!&ra i(en#i)i!ar !opos#os
pro#e#ores iso$a(os. Fn)e$i:en#e, a (iv&$*a29o pe$a 8(ia (os
res&$#a(os (es#e es#&(o in!$&i& an!he#es (e!$aran(o 0&e o
$i!openo )oi !onsi(era(o ine)i!a: no #ra#aen#o (o !-n!er (e
pr's#a#a, i*noran(o os res&$#a(os posi#ivos (o p' (e #oa#e.
) papel protetor do licopeno na pre*eno de
patologias degenerati*as
Oa revis9o sis#e1#i!a (a $i#era#&ra epi(eio$'*i!a re$a!ionan(o o
!ons&o (e #oa#e e !-n!er )oi p&+$i!a(a por Jiovann&!!i
22
. 5s#e
!ons#a#o& 0&e, en#re K2 es#&(os, 5K repor#ara asso!ia23es
inversas en#re a in*es#9o (e #oa#e e o n8ve$ (e $i!openo no san*&e
e o ris!o (e !-n!er n& $o!a$ (e)ini(o ana#oi!aen#e. Dos 5K, e
B5, as asso!ia23es inversas )ora es#a#is#i!aen#e si*ni)i!a#ivas.
;enh& (os es#&(os !i#a(os in(i!o& 0&e o a$#o !ons&o o& a$#o
n8ve$ (e $i!openo no san*&e a&en#ara !onsi(erave$en#e o ris!o
(e !-n!er e 0&a$0&er (as $o!a$i:a23es inves#i*a(as. A evi(6n!ia
+en.)i!a )oi aior para #&ores (e pr's#a#a, p&$9o e es#4a*o.
As (a(os #a+. s&*erira +ene)8!ios para #&ores (e p-n!reas,
!o$o e re#o, es4)a*o, !avi(a(e ora$, aa e !o$o (o ,#ero.
Jiovann&!!i s&*ere 0&e o $i!openo po(e !on#ri+&ir para es#es
e)ei#os +en.)i!os (os a$ien#os !on#en(o #oa#e, as isso n9o )oi
!on!$&sivo. A(eais, !oo )oi (is!&#i(o a!ia, as proprie(a(es
an#i!-n!er po(e ser e7p$i!a(as pe$a in#era29o en#re os (iversos
!oponen#es en!on#ra(os nos #oa#es. %-n!er (e pr's#a#a
!on#in&a a ser o )o!o (a pes0&isa !o $i!openo e, a par#ir (a
revis9o (e Jiovann&!!i, (iversas novas pes0&isas #6 s&r*i(o na
$i#era#&ra.
;&a e#a-an1$ise p&+$i!a(a re!en#een#e, 5#inan e# a$.
2B
,
ava$io&-se a a)ira29o (e 0&e a in*es#a (e pro(&#os (o #oa#e
re(&: o ris!o (e !-n!er (e pr's#a#a. As pes0&isa(ores revisara 2@
es#&(os envo$ven(o a in*es#a (i1ria (e &a por29o o& ais (o
$e*&e, (e se&s pro(&#os (eriva(os o& s&p$een#os (e $i!openo.
As res&$#a(os !on)ira a e)i!i6n!ia (os esos na preven29o T
(oen2a. 5n#re#an#o, es#e e)ei#o . o(es#o, $ii#an(o-se a @@H (e
re(&29o no ris!o (e !-n!er, e !on(i!iona(o a in*es#9o (o #oa#e
e *ran(e 0&an#i(a(e. A(eais, o e)ei#o preven#ivo )oi & po&!o
ais e$eva(o para a$#a in*es#a (e pro(&#os (e #oa#e !o:i(os 0&e
para a (e #oa#es !r&s. Provave$en#e (evi(o a +io(isponi+i$i(a(e
(o $i!openo, 0&e . a&en#a(a !o o pro!essaen#o, o !a$or e a
presen2a (e *or(&ras
@6, 24
. Eoi previaen#e repor#a(o 0&e h1 +ai7a
!orre$a29o en#re !ons&o (e $i!openo na (ie#a e n8ve$ s.ri!o,
25
possive$en#e (evi(o T sa#&ra29o (a a+sor29o !o a$#os n8veis (o
!aro#en'i(e in*eri(o. Por., & in#enso e)ei#o preven#ivo )oi
o+serva(o e es#&(os 0&e e(ira (ire#aen#e o $i!openo
p$as1#i!o, !opara#ivaen#e T0&e$es 0&e es#iara a in*es#a (e
$i!openo. As a&#ores !on!$&8ra 0&e pes0&isas a(i!ionais s9o
ne!ess1rias para (e#erinar o #ipo e a 0&an#i(a(e (e pro(&#os (o
#oa#e e se&s pap.is na preven29o (o !-n!er (e pr's#a#a.
Oa inves#i*a29o e!o$'*i!a >es#a#8s#i!a (e v1rios pa8ses? #e
en!on#ra(o &a re(&29o nos ris!os (e !-n!er (e pr's#a#a
re$a!iona(o ao #oa#e, prin!ipa$en#e (evi(o T a29o (o $i!openo
26
.
A$#as in*es#as (e $i!openo )ora asso!ia(as !o re(&:i(o ris!o (e
!-n!er *1s#ri!o
2K
. 5 s.rie in#e*ra(a (e es#&(os na F#1$ia
2G
, o
!ons&o (e #oa#e os#ro& &a !onsis#en#e re$a29o inversa !o o
ris!o (e neop$asia (o #ra#o (i*es#ivo >!res!ien#o #e!i(&a$ anora$,
#&or?. Dois (e pe0&ena es!a$a, a+os es#&(os (e in#erven29o
pre$iinar e pa!ien#es !o !-n!er (e pr's#a#a )ora !on(&:i(os
!o prepara23es na#&rais (e #oa#e. 5 & (e$es, %hen e# a$.
29
(eons#ro&-se 0&e, ap's a in#erven29o (ie#.#i!a, as !on!en#ra23es
s.ri!as e pros#1#i!as (e $i!openo )ora a&en#a(as e o (ano
o7i(a#ivo ao D;A (e $e&!'!i#os e #e!i(o pros#1#i!o )ora
si*ni)i!a#ivaen#e re(&:i(os. A$. (o ais, n8veis s.ri!os (e
an#8*eno pros#1#i!o espe!8)i!o >PSA? (iin&8ra. ;o o&#ro es#&(o,
L&!&M e# a$.
B0
, )oi repor#a(o 0&e a s&p$een#a29o !o e7#ra#o (e
#oa#e e hoens !o !-n!er (e pr's#a#a o(&$a a in#ensi(a(e e
o vo$&e (a neop$asia in#ra-epi#e$ia$ pros#1#i!a e (o #&or, o n8ve$
s.ri!o (e PSA e o n8ve$ (e +ioar!a(ores (o !res!ien#o e
(i)eren!ia29o !e$&$ar. A a$#a in*es#a (e $i!openo )oi #a+.
asso!ia(a ao +ai7o ris!o (e !-n!er (e aa e &$heres.
B@, B2
+oena card(aca coronariana
Doen2a !ar(8a!a !oronariana >D%%? . &a (as !a&sas pri1rias
(e or#e no &n(o o!i(en#a$. A 6n)ase (a pes0&isa h1 &i#o #e
si(o na re$a29o en#re n8veis s.ri!os (e !o$es#ero$ e ris!o (e D%%.
/ais re!en#een#e, o es#resse o7i(a#ivo in(&:i(o por esp.!ies
rea#ivas (e o7i*6nio >5UAS? )oi #a+. !onsi(era(o & ipor#an#e
)a#or na e#io$o*ia (es#a (oen2a. A $i!openo (a (ie#a #e os#ra(o
e es#&(os in vitro 0&e previne a )ora29o (e LDL o7i(a(a,
!oponen#e !have na pa#o*6nese (a a#eros!$erose e D%%.
@2
A
)on#e (e $i!openo &#i$i:a(a na aioria (esses es#&(os )oi #an#o (e
pro(&#os a$ien#8!ios (eriva(os (o #oa#e 0&an#o e7#ra#os (e
$i!openo (eriva(os (o $e*&e. A+as as )on#es !on#6 o&#ros
!aro#en'i(es e (iversas propor23es a$. (o $i!openo. ;9o .
poss8ve$, por#an#o, a#ri+&ir soen#e ao $i!openo os e)ei#os
o+serva(os.
A evi(6n!ia 0&e s&por#a o pape$ (o $i!openo na preven29o (e D%%
+aseia-se priariaen#e nas o+serva23es epi(eio$'*i!as (e
pop&$a23es norais e (e ris!o. A ais e7pressiva evi(6n!ia
+asea(a e pop&$a23es ve (e & es#&(o &$#i!6n#ri!o (e !asos-
!on#ro$e I o es#&(o 5OUA/F%, 0&e ava$io& a re$a29o en#re o es#a(o
an#io7i(an#e e in)ar#o a*&(o (o io!1r(io e in(iv8(&os (e (e:
pa8ses e&rope&s. Ap's o aC&s#e (e &a *aa (e vari1veis
(ie#.#i!as, soen#e os n8veis (e $i!openo, n9o os (e +e#a-!aro#eno,
apresen#ara !ar1#er preven#ivo.
BB
5s#e res&$#a(os )ora #a+.
!on)ira(os pe$o es#&(o Uo##er(a.
B4
%on!en#ra23es s.ri!as (e $i!openo po(e in#er)erir nos es#1*ios
ini!iais (a a#eros!$erose. A&en#an(o a espess&ra (a in#ia-e(ia
>a ais in#erna !aa(a (e & vaso san*&8neo, in!$&in(o a e(ia,
)ai7a &s!&$ar na pare(e (o vaso san*&8neo? #e (eons#ra(o
prevenir even#os !oron1rios. Oa +ai7a !on!en#ra29o s.ri!a (e
$i!openo, preva$en#e no $es#e (a Ein$-n(ia, )oi asso!ia(a !o &
a&en#o na espess&ra (a in#ia-e(ia.
B5, B6
As pop&$a23es (a
Li#&-nia e S&.!ia apresen#a #a7as (e or#a$i(a(e por D%%
(iver*en#es. ;8veis +ai7os (e $i!openo san*&8neo #6 si(o
asso!ia(os !o a&en#o no ris!o (e D%%
BK
. Ue!en#een#e &
es#&(o prospe!#ivo, (e !asos-!on#ro$e, )oi !on(&:i(o por
pes0&isa(ores (a Oniversi(a(e (e Rarvar( e B9.GK6 &$heres. A
pes0&isa os#ro& 0&e !on!en#ra23es a$#as (e $i!openo p$as1#i!o
)ora asso!ia(as !o +ai7o ris!o (e (oen2as !ar(iovas!&$ares e
&$heres (e eia e #er!eira i(a(es.
BG
A(eais, !oo o+serva(o
previaen#e pe$o eso *r&po,
B9
as poss8veis asso!ia23es
inversas !o (oen2a !ar(iovas!&$ar e a$#os n8veis (e pro(&#os
(eriva(os (e #oa#e >par#i!&$aren#e o$ho (e #oa#e e pi::a?,
s&*ere 0&e o $i!openo (a (ie#a o& o&#ros )i#o0&8i!os !ons&i(os
!oo pro(&#os (e #oa#e o$eosos o& !on#en(o '$eo !on)ere
+ene)8!ios !ar(iovas!&$ares.
,roteo d-rmica
Pro#e#ores so$ares orais s9o provave$en#e ais e)i!ien#es 0&e os
#'pi!os, (es(e 0&e a aior par#e (a e7posi29o so$ar . in!i(en#a$ e
re$a!iona(a T vi(a (i1ria e n9o (&ran#e as ).rias 0&an(o pro#e#ores
so$ares #'pi!os s9o !o&en#e &sa(os
40
>5s#a hip'#ese n9o es#1
a(e0&a(aen#e inves#i*a(a e !on)ira(a?. 5s#&(os s9o es!assos.
5n#re#an#o, h1 e)ei#o pro#e#or (e s&p$een#os orais (e !aro#en'i(es
!on#ra respos#as !&#-neas T e7posi29o so$ar. 5s#es e)ei#os
pro#e#ores po(e es#ar re$a!iona(os Ts proprie(a(es an#io7i(an#es
(os !aro#en'i(es. D&ran#e a irra(ia29o &$#ravio$e#a >OP?, a pe$e .
e7pos#a ao (ano o7i(a#ivo in(&:i(o pe$a )ora29o (e 5UAS. A
(ano )o#oo7i(a#ivo a)e#a os $ip8(eos !e$&$ares, pro#e8nas, e D;A e
es#1 envo$vi(o na )ora29o (o eri#ea I enve$he!ien#o prea#&ro
(a pe$e, )o#o(era#oses e !-n!er (e pe$e.
%aro#en'i(es, espe!ia$en#e $i!openo, s9o e)i!ien#es
se0<es#ra(ores (e 5UAS
40
. Diversos es#&(os e aniais e
e7perien#os in vitro !oprovara 0&e !aro#en'i(es e #o!o)er'is
previne $es3es (e pe$e in(&:i(as por ra(ia29o OP e pro#e*e
!on#ra o !-n!er. %on!en#ra23es p$as1#i!as e na pe$e (iin&e
!o a irra(ia29o OP. 5n#re#an#o, !&riosaen#e, o $i!openo .
es!o$hi(o pre)eren!ia$en#e aos o&#ros !aro#en'i(es.
4@
A e7posi29o
(e &a pe0&ena 1rea (e pe$e (o an#e+ra2o T ra(ia29o res&$#o& e
re(&29o (o $i!openo (.ri!o. A esa (ose (e OP, por., n9o
res&$#o& e &(an2as si*ni)i!a#ivas no +e#a-!aro#eno (.ri!o. As
a&#ores !on!$&8ra 0&e 0&an(o a pe$e . s&+e#i(a a & es#resse
OP, ais $i!openo . (es#r&8(o 0&e +e#a-!aro#eno, s&*erin(o 0&e o
$i!openo (esepenha & pape$ ipor#an#e na re(&29o (o es#resse
o7i(a#ivo nos #e!i(os. ;o en#an#o, o&#ras in#erpre#a23es (esses
res&$#a(os s9o poss8veis.
5 pes0&isa re!en#e
40
, a e)i!1!ia (e &a is#&ra (e !aro#en'i(es
!on#en(o +e#a-!aro#eno, $&#e8na e $i!openo )oi !opara(o ao +e#a-
!aro#eno iso$a(o na pro#e29o !on#ra eri#ea !&#-neo in(&:i(o por
OP. Po$&n#1rios !a&!asianos )ora #es#a(os n& es#&(o para$e$o e
p$a!e+o-!on#ro$a(o. A in*es#a (e +e#a-!aro#eno o& (a is#&ra (e
!aro#en'i(es a&en#o& i*&a$en#e os !aro#en'i(es #o#ais na pe$e
(a seana 0 para a @2. ;enh&a &(an2a o!orre& no #o#a$ (e
!aro#en'i(es (.ri!os (o *r&po !on#ro$e. A in#ensi(a(e (o eri#ea,
24 horas ap's a irra(ia29o, )oi re(&:i(a e a+os os *r&pos 0&e
re!e+era !aro#en'i(es e )oi si*ni)i!a#ivaen#e in)erior 0&e a $inha
+asa$ ap's @2 seanas (e s&p$een#a29o. A s&p$een#a29o
pro$on*a(a por @2 seanas !o 24 *S(ia (e &a is#&ra (e
!aro#en'i(es apor#an(o 0&an#i(a(es sii$ares (e +e#a-!aro#eno,
$&#e8na e $i!openo e$hora o eri#ea in(&:i(o por OP e h&anos.
A aior e)i!1!ia (a is#&ra po(e ser !onse0<6n!ia (as (i)eren#es
a+sor23es (e !oprien#os (e on(a (as v1rios s&+s#-n!ias,
res&$#an(o n& aior po#en!ia$ para &a ap$a *aa (e
!oprien#os (e on(a. 5 o&#ro es#&(o, o eso *r&po (e
pes0&isa (eons#ro& 0&e a s&p$een#a29o !o #oa#e, &a )on#e
na#&ra$ (e $i!openo, e o&#ros !aro#en'i(es >Ei*&ra @? #a+.
pro#e*e !on#ra eri#ea (.ri!o in(&:i(o por OP e h&anos.
42
.ecanismo de ao
a" Ati*idade antio/idante
A es#resse o7i(a#ivo . re!onhe!i(o !oo & (os aiores
respons1veis para o a&en#o (o ris!o (e (oen2as !ar(iovas!&$ares
e !-n!er. Den#re os !aro#en'i(es ais !o&ns, o $i!openo
apresen#a a ais po#en#e a#ivi(a(e an#io7i(an#e (eons#ra(a e
es#&(os e7perien#ais in vitro
@
. De a!or(o !o esse es#&(o, a
po#6n!ia an#io7i(an#e (os !aro#en'i(es po(e ser !$assi)i!a(a e:
$i!openo #e po#6n!ia aior 0&e a (e a$)a-#o!o)ero$ 0&e, por s&a
ve:, . aior (o 0&e a (e a$)a-!aro#eno, sen(o essa aior (o 0&e a
(e +e#a-!rip#o7an#ina, 0&e s&pera a (e :ea7an#ina, aior (o 0&e a
(o +e#a-!aro#eno, 0&e s&pera a (a $&#e8na. /is#&ras (e !aro#en'i(es
)ora ais e)e#ivas 0&e !opos#os iso$a(os.
@9
5s#e e)ei#o )oi ais
pron&n!ia(o 0&an(o $i!openo o& $&#e8na es#ava presen#es. A
po#en!ia$ preven#ivo s&perior (e is#&ras po(e es#ar re$a!iona(a
!o o posi!ionaen#o espe!8)i!o (os (i)eren#es !aro#en'i(es nas
e+ranas !e$&$ares.
Diversos es#&(os so+re o !ons&o (o #oa#e (eons#rara
proprie(a(es an#io7i(an#es e h&anos. Por e7ep$o,
re!en#een#e )oi !ons#a#a(o 0&e o !ons&o (i1rio (e pro(&#os (o
#oa#e, !on#en(o @5 * (e $i!openo, a$ia(o a o&#ros )i#on&#rien#es
(o eso, a&en#ara si*ni)i!a#ivaen#e a pro#e29o Ts
$ipopro#e8nas (o es#resse o7i(a#ivo ex vivo
4B
. 5s#es res&$#a(os
in(i!a 0&e o $i!openo a+sorvi(o (e pro(&#os (e #oa#e a#&a !oo
an#io7i(an#e in vivo.
b" Inibio da proliferao celular neopl0sica 1ciclo
celular2
Li!openo #e (eons#ra(o ini+i29o (a pro$i)era29o (e (iversos
#ipos (e !.$&$as !an!erosas, in!$&in(o as (e aa, pr's#a#a,
p&$9o, e en(o.#rio. A e)ei#o ini+i#'rio (o $i!openo no !res!ien#o
!e$&$ar (e !-n!er (e aa e pr's#a#a n9o )oi a!opanha(o (e
or#e !e$&$ar apop#'#i!a >pro*raa(a? o& ne!r'#i!a >res&$#an#e (e
inC,ria o& (oen2a?, e!aniso re$a!iona(o T a29o (e !er#as (ro*as,
as n9o a i!ron&#rien#es )re0<en#een#e !ons&i(os na (ie#a
h&ana. 5s#e e)ei#o )oi a!opanha(o (e ini+i29o na pro*ress9o (o
!i!$o !e$&$ar (a )ase JASJ@ a )ase S, e(i(a por !i#oe#ria (e
)$&7oB. A ini+i29o (a pro$i)era29o !e$&$ar es#1 re$a!iona(a !o a
re(&29o nos n8veis (e pro#e8na !i!$ina D@, 0&e . & re*&$a(or
!have nes#e pro!esso. 5s#1 +e (o!&en#a(o 0&e )a#ores (e
!res!ien#o a)e#a o apara#o (o !i!$o !e$&$ar >priariaen#e
(&ran#e a )ase J@? e as !i!$inas #ipo-D
44
s9o os prin!ipais
!oponen#es 0&e a#&a !oo sensores (os )a#ores (e
!res!ien#o. A(eais, a !i!$ina D@ . !onhe!i(a por a*ir !oo &
on!o*ene >& *ene 0&e (esre*&$a(o #rans)ora !.$&$as norais
e !an!erosas? e #e si(o en!on#ra(a e7!essivaen#e e7pressa(a
e &i#as $inha*ens (e !.$&$as (e !-n!er (e aa +e !oo e
#&ores pri1rios
45
. Por#an#o, a re(&29o no n8ve$ (e !i!$ina D@ na
!.$&$a pe$o $i!openo )orne!e &a e7p$i!a29o para o e!aniso (a
a#ivi(a(e an#i!-n!er (o !aro#en'i(e.
c" Interfer&ncia com a estimulao de fatores de
crescimento da proliferao de c-lulas cancerosas
A es#i&$a29o (o !res!ien#o (e !.$&$as a1rias !an!erosas pe$o
)a#or (e !res!ien#o @ >FJE-@?, see$han#e T ins&$ina, )oi
ar!a(aen#e re(&:i(a por !on!en#ra23es )isio$'*i!as (e $i!openo
e es#&(os e7perien#ais in vitro.
2, 46
A ipor#-n!ia (es#e a!ha(o
para a preven29o (o !-n!er es#1 re$a!iona(a a a!ha(os
epi(eio$'*i!os in(epen(en#es 0&e re$a!iona a e$eva29o (e
n8veis (e FJE-@ ao a&en#o (o ris!o (e !-n!er (e aa e pr's#a#a
(&ran#e a vi(a.
4K, 4G
%onsi(eran(o a a)ira29o (e 0&e o $i!openo
in#er)ere !o a FJE-@ e a es#i&$a29o (o !res!ien#o !e$&$ar
#&ora$, !on)ira(a e es#&(os !$8ni!os, #e-se & o#ivo ra!iona$
para re!oen(ar o a&en#o (a in*es#a (e $i!openo, espe!ia$en#e
via pro(&#os a$ien#8!ios (eriva(os (o #oa#e, para preven29o (o
!-n!er.
d" ,re*eno do c3ncer por induo de en4imas da
fase II
A in(&29o (e en:ias (a )ase FF, 0&e !onC&*a e$e#r')i$os rea#ivos
>s&+s#-n!ias 0&8i!as 0&e #6 a)ini(a(e por e$.#rons o& #en(e a
a!ei#ar e$.#rons (e o&#ras? e a*e !oo an#io7i(an#es in(ire#os,
pare!e ser &a )ora e)e#iva (e o+#er pro#e29o !on#ra (iversos
!ar!ino*6ni!os e aniais e h&anos. 5 "h&vanesQari e# a$.
49
,
asso!io&-se o e)ei#o 0&iio-preven#ivo >preven#ivo (o !-n!er? (o
$i!openo na in!i(6n!ia (e #&ores na !avi(a(e ora$ in(&:i(os por
D/"A >+o!he!ha, +o!a? !o & si&$#-neo a&en#o no n8ve$ (e
*$&#a#ion re(&:i(o, en:ias (o !i!$o re(&#or (o *$&#a#ion e *$&#a#ion
S-#rans)erase >JSD? na &!osa +&!a$. >;o#a: D/"A . & 9,@0-
(ie#i$+en:-a-an#ra!eno, & po#en#e !opos#o !ar!ino*6ni!o?.
5s#es res&$#a(os s&*ere 0&e o a&en#o nos n8veis (e JSR e (a
en:ia JSD (a )ase FF in(&:i(o pe$o $i!openo ina#iva !ar!ino*6ni!os
por )orar !onC&*a(os >s&+s#-n!ias 0&8i!as )ora(as por (ois o&
ais !oponen#es?, pro(&#os 0&e s9o enos #'7i!os e rapi(aen#e
e7!re#a(os.
e" %egulao da transcrio
Drans!ri29o . o pro!esso pe$o 0&a$ a in)ora29o *en.#i!a .
!arrea(a (a o$.!&$a (o D;A por eio (o U;A 0&e a#&a !oo
ensa*eiro. 5ssa via +io0&8i!a $eva a )ora29o (e novas
pro#e8nas pe$o pro!esso !haa(o (e #rans$a29o. %oo (is!&#i(o
a!ia, o $i!openo o(&$a os e!anisos +1si!os (e pro$i)era29o
!e$&$ar, (e sina$i:a29o (e )a#ores (e !res!ien#o e (a !o&ni!a29o
in#er!e$&$ar C&n!iona$
50
. A(i!iona$en#e, o $i!openo pro(&:
o(i)i!a23es na e7press9o (e &i#as pro#e8nas 0&e par#i!ipa
(esses pro!essos, por e7ep$o, !one7inas, !i!$inas e en:ias (a
)ase FF. 5n#re#an#o, apare!e a se*&in#e in#erro*a29o: =Por 0&ais
e!anisos o $i!openo in#er)ere !o #an#as e (iversas vias
+io0&8i!as !e$&$aresW= As o(i)i!a23es na e7press9o (e ,$#ip$as
pro#e8nas s&*ere 0&e o e)ei#o ini!ia$ (o $i!openo envo$ve a
o(&$a29o (a #rans!ri29o. 5s#e pro!esso . revisa(o por Sharoni e#
a$. e re!en#e p&+$i!a29o
5@
. Provave$en#e, (evi(o T in#era29o (as
o$.!&$as (e !aro#en'i(es o& (e se&s (eriva(os !o os )a#ores (e
#rans!ri29o >e.*., !o re!ep#ores n&!$eares a#iva(ores (e $i*a29o
52
?
o& o(i)i!a29o in(ire#a (a a#ivi(a(e #rans!ri!iona$ >e.*., via
o(i)i!a23es no pa(r9o !e$&$ar re(o7, 0&e a)e#a os sis#eas re(o7-
sens8veis (e #rans!ri29o
5B
?.
5egurana do licopeno
A per)i$ (e se*&ran2a #e a#ra8(o &i#a a#en29o ap's a p&+$i!a29o
(e ensaios !o s&p$een#a29o (e +e#a-!aro#eno, 0&e os#rara
res&$#a(os ne*a#ivos. N in#eressan#e 0&e o a&en#o no ris!o (e
!-n!er (e p&$9o nesses es#&(os )oi re$a!iona(o a & a&en#o (e
@2 a @6 ve:es nos n8veis p$as1#i!os (e +e#a-!aro#eno (evi(o T
s&p$een#a29o >es#&(os (e %AU5D e AD"%, respe!#ivaen#e
54
?.
;es#es es#&(os, os n8veis (e +e#a-!aro#eno p$as1#i!os
a&en#ara (e 0.B2 X/, an#es (a s&p$een#a29o, para B.9 e 5.9
X/, respe!#ivaen#e. >;o#a: O i!ro/o$ar YX/Z (eno#a &a
!on!en#ra29o (e @ 7 @0-6 peso (o *raa (e so$&#o por $i#ro (e
so$&29o.? ;& #er!eiro es#&(o, 0&e n9o os#ro& e)ei#o (a
s&p$een#a29o !o +e#a-!aro#eno >Physi!ians Rea$#h S#&(y?,
54
)oi
en!on#ra(o soen#e & a&en#o (e !in!o ve:es no n8ve$ s.ri!o (e
!aro#en'i(e. %&riosaen#e, & ,ni!o es#&(o !o res&$#a(os
posi#ivos ap's a s&p$een#a29o !o +e#a-!aro#eno )oi rea$i:a(o e
Lin7ian, &a !o&ni(a(e !hinesa !o n8veis (e !aro#en'i(es &i#o
+ai7os >0.@@ X/? an#es (a in#erven29o
54
. Apesar (a s&p$een#a29o
#er !a&sa(o & a&en#o (e @@ ve:es no n8ve$ (e +e#a-!aro#eno, a
!on!en#ra29o )ina$ en!on#ra(a )oi re$a#ivaen#e +ai7a: @.5 /.
Do(os esses es#&(os &#i$i:ara +e#a-!aro#eno sin#.#i!o. Por#an#o,
an#er os n8veis p$as1#i!os (e !aro#en'i(es na )ai7a s&perior (os
n8veis )isio$'*i!os, as n9o a!ia, po(e ser & in(i!a(or se*&ro. N
in#eressan#e 0&e, ao rever v1rios es#&(os 0&e e(ira n8veis
s.ri!os (e +e#a-!aro#eno e $i!openo ap's s&p$een#a29o, os n8veis
s.ri!os (e +e#a-!aro#eno apare!e si*ni)i!a#ivaen#e ais
e$eva(os 0&e os en!on#ra(os para o $i!openo. As n8veis s.ri!os
en!on#ra(os para +e#a-!aro#eno es#9o e #orno (e B / e po(e
e7!e(er 5 / ap's s&p$een#a29o. Por o&#ro $a(o, n8veis (e
$i!openo a!ia (e @.2 / s9o raraen#e vis#os, eso ap's
&#i$i:a29o por $on*o pra:o. A$. (o ais, o n8ve$ s.ri!o (e $i!openo
en!on#ra(o n9o )oi (ire#aen#e re$a!iona(o ao a&en#o (e
!aro#en'i(e s&p$een#a(o. Por e7ep$o, s&p$een#a29o #9o a$#a
!oo K5 *S(ia n9o e$evo& os n8veis s.ri!os (e $i!openo ais 0&e
@ /.
55, 56
%on!$&in(o, por a$*& e!aniso (es!onhe!i(o, os
n8veis p$as1#i!os (e $i!openo ap's a s&p$een#a29o perane!e
re$a#ivaen#e +ai7os, o 0&e po(e !ons#i#&ir &a v1$v&$a (e
se*&ran2a.
Diversos es#&(os (e se*&ran2a !o prepara23es sin#.#i!as (e
$i!openo )ora rea$i:a(os e ra#os e !oe$hos. As res&$#a(os (es#es
es#&(os (eons#rara a a&s6n!ia (e 0&a$0&er e)ei#o #'7i!o
si*ni)i!a#ivo (os a#eriais #es#a(os nos aniais
5K-59
. 5n#re#an#o, o
%oi#6 %ien#8)i!o (e A$ien#os (a %oiss9o 5&rop.ia C&$*o& essas
prepara23es sin#.#i!as ina!ei#1veis para &so a$ien#ar (evi(o a s&a
a$#a sensi+i$i(a(e ao o7i*6nio e a $&:, 0&e )ora pro(&#os (e
(e*ra(a29o !o a#ivi(a(e &#a*6ni!a
60
. Oa ap$a revis9o (a
se*&ran2a por & *r&po in(epen(en#e (e #o7i!o$o*is#as res&$#o&
n&a JUAS >*enera$$y re!o*ni:e( as sa)e?, a&#o-a)ira29o para
Ly!-A-/a#o
[
>Ly!oUe(, "eer-Sheva, Fsrae$?, &a is#&ra (e e7#ra#o
(e #oa#e 0&e #e si(o o+Ce#o (e v1rios (os es#&(os 0&e #6
ava$ia(o os e)ei#os (os pro(&#os (es#e )r&#o e )ora (e
s&p$een#o (ie#.#i!o n&a varie(a(e (e par-e#ros pa#o$'*i!os.
6@
6oncluses
A pes0&isa !ien#8)i!a a#&a$ #e (eons#ra(o &a *aa (e
+ene)8!ios T sa,(e !$araen#e asso!ia(os aos pro(&#os (o #oa#e
na (ie#a. A ava$ia29o (a siner*ia en#re !aro#en'i(es #e
(eons#ra(o 0&e ne $i!openo sin#.#i!o ne iso$a(o (o #oa#e
a#&a !oo &a =+a$a 1*i!a=. 5)i!1!ia e se*&ran2a es#9o
in#iaen#e re$a!iona(as ao #oa#e in#eiro. As +ene)8!ios T sa,(e
s9o (eriva(os (a a(i29o (e pro(&#os (o #oa#e T (ie#a,
par#i!&$aren#e pro(&#os (o #oa#e !o:i(os e !on#en(o '$eo, o& (e
s&p$een#os (e e7#ra#os (e #oa#e e s&spens9o o$eosa. A '$eo
na#&ra$ (o #oa#e a&en#a a +io(isponi+i$i(a(e (os se&s
)i#on&#rien#es. Para & +ene)8!io 17io, &s&1rios (e s&p$een#os
(ie#.#i!os 0&e op#ara por &a nova a+or(a*e n&#ri!iona$ (eve
!onsi(erar pro(&#os !on#en(o & e7#ra#o (e #oa#e pa(roni:a(o
0&e )orne2a os (iversos )i#on&#rien#es a#ivos (o #oa#e.
Joseph Levy, PhD e Yoav Sharoni, PhD so professores do
Departmento de Bioqumica Cnica, !acudade de Ci"ncias da
Sa#de, $niversidade Ben%&urion do Centro '(dico )e*ev e
Soro+a de ,upat -oim, Beer%Sheva, .srae/
raduo: %oberto 'oorhem
%efer&ncias
0/ Di 'ascio P, ,aiser S, Sies -/ Lycopene as the most efficient 1ioo*ica
carotenoid sin*et oxy*en quencher/ 2rch Biochem Biophys/
0343567896:;<=6%<=4/
6/ Levy J, Bosin >, !edman B, et a/ Lycopene is a more potent inhi1itor of
human cancer ce proiferation than either a%carotene or 1%carotene/
)utr Cancer/ 033<568;6<7%6?7/
=/ )ahum 2, -irsch ,, Danien+o ', et a/ Lycopene inhi1ition of ce cyce
pro*ression in 1reast and endometria cancer ces is associated @ith
reduction in cycin D eves and retention of p679,ip0: in the cycin >%
cd+6 compexes/ Anco*ene/ 6BB056B96?:;=864%=8=?/
8/ Chan* LD, Cooney EF, Bertram JS/ Carotenoids up%re*uate connexin%
8= *ene expression independent of their provitamin%2 or antioxidant
properties/ Cancer Ees/ 03365<696B:;<7B7%<706/
</ Ben%Dor 2, )ahum 2, Danien+o ', et a/ >ffects of acyco%retinoic acid
and ycopene on activation of the retinoic acid receptor and proiferation
of mammary cancer ces/ 2rch Biochem Biophys/ 6BB05=3090:;63<G=B6/
?/ Han* DD, Liu C, Bronson EI, Smith D>, ,rins+y )., Eusse '/ Eetinoid
si*nain* and activator protein%0 expression in ferrets *iven 1eta%
carotene suppements and exposed to to1acco smo+e/ J )at Cancer
.nst/ 033353090:;?B%??/
7/ $SD2/ 0334/ $SD2%)C. Carotenoid Data1ase for $/S/ !oods/ )utrient
Data La1/, 2*ric/ Ees/ Service, $/S/ Dept/ of 2*ricuture, Betsvie
-uman )utrition Eesearch Center, Eiverdae, 'D/
4/ )*uyen 'L, Sch@artJ SJ/ Lycopene sta1iity durin* food processin*/
Proc Soc >xp Bio 'ed/ Jun 0334560496:;0B0%0B</
3/ -adey CH, 'ier >C, Sch@artJ SJ, Cinton S,/ Iomatoes, ycopene,
and prostate cancer; pro*ress and promise/ >xp Bio 'ed 9'ay@ood:/
)ov 6BB6566790B:;4?3%44B/
0B/ 'an*es 2E, -oden J', Beecher &E, !orman 'E, LanJa >/ Carotenoid
content of fruits and ve*eta1es; an evauation of anaytic data/ J/ 2m/
Diet 2ssoc/ 033=53=;648%63?/
00/ Bohm F, Bitsch E/ .ntestina a1sorption of ycopene from different
matrices and interactions to other carotenoids, the ipid status, and the
antioxidant capacity of human pasma/ >ur J )utr/ Jun 03335=49=:;004%
06</
06/ !uhrman B, Ben%Yaish L, 2ttias J, -aye+ I, 2viram '/ Iomato ycopene
and 1eta%carotene inhi1it o@ density ipoprotein oxidation and this effect
depends on ipoprotein vitamin > content/ )utr 'eta1 Cardiovasc Dis/
033757;8==%88=/
0=/ !uhrman B, >is 2, 2viram '/ -ypochoesteroemic effect of ycopene
and 1eta%carotene is reated to suppression of choestero synthesis and
au*mentation of LDL receptor activity in macropha*es/ Biochem Biophys
Ees Commun/ 033756==9=:;?<4%??6/
08/ ,hachi+ !, Carvaho L, Bernstein PS, 'uir &J, Chao DY, ,atJ )B/
Chemistry, distri1ution, and meta1oism of tomato carotenoids and their
impact on human heath/ >xp Bio 'ed 9'ay@ood:/ )ov
6BB6566790B:;48<%4<0/
0</ Hafisch Y, Hafisch S, 2*1aria E, Levy J, Sharoni Y/ Lycopene in
serum, s+in and adipose tissues after tomato%oeoresin suppementation
in patients under*oin* haemorrhoidectomy or peri%ana fistuotomy/ Br J
)utr/ Act 6BB=53B98:;7<3%7??/
0?/ Stah H, Sies -/ $pta+e of ycopene and its *eometrica isomers is
*reater from heat%processed than from unprocessed tomato Kuice in
humans/ J )utr/ 03365066900:;60?0%60??/
07/ 2mir -, ,aras ', &iat J, et a/ Lycopene and 0,6<%dihydroxyvitamin%D=
cooperate in the inhi1ition of ce cyce pro*ression and induction of
differentiation in -L%?B eu+emic ces/ )utr Cancer/ 03335==;0B<%006/
04/ Pastori ', Pfander -, Bosco1oini+ D, 2JJi 2/ Lycopene in association
@ith apha%tocophero inhi1its at physioo*ica concentrations proiferation
of prostate carcinoma ces/ Biochem Biophys Ees Commun/
033456<B9=:;<46%<4</
03/ Stah H, Jun*hans 2, deBoer B, Driomina >S, Brivi1a ,, Sies -/
Carotenoid mixtures protect mutiamear iposomes a*ainst oxidative
dama*e; syner*istic effects of ycopene and utein/ !>BS Lett/
0334586796:;=B<%=B4/
6B/ Boieau IH, Liao C, ,im S, Lemesho@ S, >rdman JH Jr, Cinton S,/
Prostate carcino*enesis in )%methy%)%nitrosourea 9)'$:%testosterone%
treated rats fed tomato po@der, ycopene, or ener*y%restricted diets/ J
)at Cancer .nst/ )ov < 6BB=53<960:;0<74%0<4?/
60/ &ann P-, ,hachi+ !/ Iomatoes or ycopene versus prostate cancer; is
evoution anti%reductionistL J )at Cancer .nst/ )ov < 6BB=53<960:;0<?=%
0<?</
66/ &iovannucci >/ Iomatoes, tomato%1ased products, ycopene, and
cancer; revie@ of the epidemioo*ic iterature/ J )at Cancer .nst/
0333530;=07%==0/
6=/ >tminan ', Ia++ouche B, Caamano%.sorna !/ Ihe roe of tomato
products and ycopene in the prevention of prostate cancer; a meta%
anaysis of o1servationa studies/ Cancer >pidemio Biomar+ers Prev/
'ar 6BB850=9=:;=8B%=8</
68/ &iovannucci >, 2scherio 2, Eimm >B, Stampfer 'J, CoditJ &2, Hiett
HC/ .nta+e of carotenoids and retino in reation to ris+ of prostate
cancer/ J )at Canc .nst/ 033<547;07?7%077?/
6</ !reeman FL, 'eydani ', Yon* S, et a/ Prostatic eves of tocopheros,
carotenoids, and retino in reation to pasma eves and sef%reported
usua dietary inta+e/ 2m J >pidemio/ Jan 0< 6BBB50<096:;0B3%004/
6?/ &rant HB/ 2n ecoo*ic study of dietary in+s to prostate cancer/ 2tern
'ed Eev/ 0333589=:;0?6%0?3/
67/ Isu1ono Y, Isu*ane S, &ey ,!/ Pasma antioxidant vitamins and
carotenoids in five Japanese popuations @ith varied mortaity from
*astric cancer/ )utr Cancer/ 03335=890:;<?%?0/
64/ La Fecchia C/ Iomatoes, ycopene inta+e, and di*estive tract and femae
hormone%reated neopasms/ >xp Bio 'ed 9'ay@ood:/ )ov
6BB6566790B:;4?B%4?=/
63/ Chen L, Stace@icJ%SapuntJa+is ', Duncan C, et a/ Axidative D)2
dama*e in prostate cancer patients consumin* tomato sauce%1ased
entrees as a @hoe%food intervention/ J )at Cancer .nst/
6BB053=968:;0476%0473/
=B/ ,ucu+ A, Sar+ar !-, Sa+r H, et a/ Phase .. randomiJed cinica tria of
ycopene suppementation 1efore radica prostatectomy/ Cancer
>pidemio Biomar+ers Prev/ 6BB050B94:;4?0%4?4/
=0/ Eonco 2, De Stefani >, Boffetta P, Deneo%Pee*rini -, 'endiaharsu ',
Le1or*ne !/ Fe*eta1es, fruits, and reated nutrients and ris+ of 1reast
cancer; a case%contro study in $ru*uay/ )utr Cancer/ 03335=<96:;000%
003/
=6/ -uten ,, Fan ,appe 2L, Hin+vist 2, et a/ Carotenoids, apha%
tocopheros, and retino in pasma and 1reast cancer ris+ in northern
S@eden/ Cancer Causes Contro/ 2u* 6BB05069?:;<63%<=7/
==/ ,ohmeier L, ,ar+ JD, &omeJ&racia >, et a/ Lycopene and myocardia
infarction ris+ in the >$E2'.C Study/ 2m J >pidemio/ 0337508?;?04%
?6?/
=8/ ,ipstein%&ro1usch ,, Launer LJ, &eeiKnse J', Boein* -, -ofman 2,
Hitteman JC/ Serum carotenoids and atheroscerosis/ Ihe Eotterdam
Study/ 2theroscerosis/ 6BBB508490:;83%<?/
=</ Eissanen I-, Foutiainen S, )yyssonen ,, et a/ Lo@ serum ycopene
concentration is associated @ith an excess incidence of acute coronary
events and stro+e; the ,uopio .schaemic -eart Disease Eis+ !actor
Study/ Br J )utr/ 6BB054<9?:;783%7<8/
=?/ Eissanen I-, Foutiainen S, )yyssonen ,, Saonen E, ,apan &2,
Saonen JI/ Serum ycopene concentrations and carotid atheroscerosis;
the ,uopio .schaemic -eart Disease Eis+ !actor Study/ 2m J Cin )utr/
Jan 6BB=57790:;0==%0=4/
=7/ ,ristenson ', Cieden B, ,ucins+iene C, et a/ 2ntioxidant state and
mortaity from coronary heart disease in Lithuanian and S@edish men;
concomitant cross sectiona study of men a*ed <B/ B'J/
03375=0897B40:;?63%?==/
=4/ Sesso -D, Burin* J>, )or+us >P, &aJiano J'/ Pasma ycopene, other
carotenoids, and retino and the ris+ of cardiovascuar disease in @omen/
2m J Cin )utr/ Jan 6BB857390:;87%<=/
=3/ Sesso -D, Liu S, &aJiano J', Burin* J>/ Dietary ycopene, tomato%
1ased food products and cardiovascuar disease in @omen/ J )utr/ Ju
6BB=50==97:;6==?%6=80/
8B/ -einrich $, &artner C, Hie1usch ', et a/ Suppementation @ith 1eta%
carotene or a simiar amount of mixed carotenoids protects humans from
$F%induced erythema/ J )utr/ Jan 6BB=50==90:;34%0B0/
80/ Ei1aya 'ercado JD, &armyn ', &ichrest B2, Eusse E'/ S+in
ycopene is destroyed preferentiay over 1eta%carotene durin* utravioet
irradiation in humans/ J )utr/ 033<506<97:;04<8%04<3/
86/ Stah H, -einrich $, Hiseman S, >icher A, Sies -, Ironnier -/ Dietary
tomato paste protects a*ainst utravioet i*ht%induced erythema in
humans/ J )utr/ 'ay 6BB050=09<:;0883%08<0/
8=/ -adey CH, Cinton S,, Sch@artJ SJ/ Ihe consumption of processed
tomato products enhances pasma ycopene concentrations in
association @ith a reduced ipoprotein sensitivity to oxidative dama*e/ J
)utr/ 'ar 6BB=50==9=:;767%7=6/
88/ Sherr CJ/ D%type cycins/ Irends Biochem Sci/ 033<56B9<:;047%03B/
8</ Buc+ey '!, S@eeney ,J, -amiton J2, et a/ >xpression and
ampification of cycin *enes in human 1reast cancer/ Anco*ene/
033=5494:;6067%60==/
8?/ ,aras ', 2mir -, !ishman D, et a/ Lycopene interferes @ith ce cyce
pro*ression and insuin%i+e *ro@th factor . si*nain* in mammary cancer
ces/ )utr Cancer/ 6BBB5=?;0B0%000/
87/ Chan J', Stampfer 'J, &iovannucci >, et a/ Pasma insuin%i+e *ro@th
factor%. and prostate cancer ris+; 2 prospective study/ Science/
03345673;<?=%<??/
84/ -an+inson S>, Hiett HC, CoditJ &2, et a/ Circuatin* concentrations
of insuin%i+e *ro@th factor . and ris+ of 1reast cancer/ Lancet/
03345=<0;0=3=%0=3?/
83/ Bhuvanes@ari F, Femuru*an B, Baasenthi S, Eamachandran CE,
)a*ini S/ Chemopreventive efficacy of ycopene on 7,06%
dimethy1enJMaNanthracene%induced hamster 1ucca pouch
carcino*enesis/ !itoterapia/ Dec 6BB057694:;4?<%478/
<B/ 2ust A, 2e%2*ha ), Chan* L, Hoersen -, Sies -, Stah H/ Lycopene
Axidation Product >nhances &ap Junctiona Communication/ !ood
Chem Ioxico/ 6BB=58090B:;0=33%08B7/
<0/ Sharoni Y, Danien+o ', Du1i ), Ben%Dor 2, Levy J/ Carotenoids and
transcription/ 2rch/ Biochem/ Biophys/ 6BB85.n press/
<6/ Stah H, von Laar J, 'artin -D, >mmerich I, Sies -/ Stimuation of *ap
Kunctiona communication; comparison of acyco% retinoic acid and
ycopene/ 2rch Biochem Biophys/ 6BBB5=7=90:;670%678/
<=/ Levy J, Ben%Dor 2, Du1i ), Danien+o ', Cic+ 2, Sharoni Y/ Carotenoids
activate the antioxidant response eement 9are: transcription system/
22CE 2nnua 'eetin*/ 6BB8;21stract 8B=</
<8/ .2EC -and1oo+ of Cancer prevention/ Fo 6 Carotenoids5 0334/
<</ 2*ar@a S, Eao 2F/ Iomato ycopene and o@ density ipoprotein
oxidation; a human dietary intervention study/ Lipids / 03345==90B:;340%
348/
<?/ Paetau ., ,hachi+ !, Bro@n >D, et a/ Chronic in*estion of ycopene%rich
tomato Kuice or ycopene suppements si*nificanty increases pasma
concentrations of ycopene and reated tomato carotenoids in humans/
2m J Cin )utr/ Dec 03345?49?:;0047%003</
<7/ 'eert H, Dec+ardt ,, &em1ardt C, Schute S, Fan EavenJ@aay B,
Sesins+i E/ Ihirteen%@ee+ ora toxicity study of synthetic ycopene
products in rats/ !ood Chem Ioxico/ )ov 6BB658B900:;0<40%0<44/
<4/ Christian 'S, Schute S, -e@i* J/ Deveopmenta 9em1ryo%feta
toxicityOterato*enicity: toxicity studies of synthetic crystaine ycopene in
rats and ra11its/ !ood Chem Ioxico/ Jun 6BB=5809?:;77=%74=/
<3/ Jon+er D, ,uper C!, !raie ), >strea 2, Eodri*ueJ Atero C/ )inety%day
ora toxicity study of ycopene from Ba+esea trispora in rats/ Ee*u
Ioxico Pharmaco/ Jun 6BB=5=79=:;=3?%8B?/
?B/ >uropean C/ Apinion on synthetic ycopene as a coourin* matter for use
in foodstuffs/ 2nnex F to the minutes of the 003th penary meetin* of the
>uropean Scientific committee on food/ 0333/
?0/ Burdoc+ &roup/ Apinion of an >xpert Pane on the &eneray
Eeco*niJed as Safe 9&E2S: status of Lyc%A%'ato P oeoresin ?Q as a
food in*redient/ Ihe Burdoc+ &roup, 'ay =0, 6BB=/
Eon#e:
h##p:SSQQQ.i+p.or*.+rSa#&a$i:a!ao!$ini!a.sh#$
Fns#i#&#o "rasi$eiro (e P$an#as /e(i!inais