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Jou nal sec ion: O al Medicine and Pa hology
Publica ion Types: Re iew
Capsaicin in ake and o al ca cinogenesis: A sys ema ic e iew
And ea Mosqueda-Solís 1, I ene La uen e-Ibáñez de Mendoza 2, José Manuel Agui e-U iza 2, Adalbe o
Mosqueda-Taylo 3
1 Depa men o Cell and Molecula Biology, Ka olinska Ins i u e , S ockholm, Sweden
2 S oma ology II Depa men , Uni e si y o he Basque Coun y (EHU), Leioa, Spain
3 Heal h Ca e Depa men , Au onomous Me opoli an Uni e si y Xochimilco, Mexico Ci y, Mexico
Co espondence:
Heal h Ca e Depa men
Au onomous Me opoli an Uni e si y Xochimilco
Mexico Ci y, Mexico
mosqueda@co eo.xoc.uam.mx
Recei ed: 06/01/2021
Accep ed: 14/01/2021
Abs ac
Backg ound: Chili is he mos hea ily and equen ly consumed spice, ei he as a la ou ing o colou ing agen ,
and i is also a majo sou ce o p o- i amin A, i amin E and C. The main capsaicinoid ound in chili peppe s is
capsaicin. I has been demons a ed ha capsaicin ac s as a cance -supp essing agen h ough i s an ioxidan and
an i-in lamma o y e ec s, by blocking se e al signal ansduc ion pa hways. O al squamous cell ca cinoma is
one o he mos p e alen cance wo ldwide. I is no ewo hy ha in coun ies whe e popula ions o di e se e hnic
g oups co-exis , di e ences ha e been obse ed in e ms o incidence o o al cance . The a iances in hei die
could explain, a leas in pa , hese di e ences. The objec i e o his sys ema ic e iew is o explo e i he e is
e idence o a possible ela ionship be ween capsaicin in ake and he incidence o o al squamous cell ca cinoma,
and discuss such associa ion.
Ma e ial and Me hods: A bibliog aphical sea ch was made in PubMed, Scopus and Web o Science da abases, and
inally 7 expe imen al s udies we e included; OHAT isk o bias ool was used o assess hei quali y.
Resul s: All he s udies con i m ha capsaicin is a chemop e en i e agen ha p e en s he de elopmen o o al
cance , h ough inhibi ion o malignan cell p oli e a ion and inc ease o apop osis.
Conclusions: Mo e human s udies a e needed in o de o cla i y he eal link be ween consump ion o chili (cap-
saicin) and he p e alence o o al cance .
Key wo ds: Chili, capsaicin, o al epi helial dysplasia, o al cance , cell p oli e a ion, apop osis.
doi:10.4317/medo al.24570
Mosqueda-Solís A, La uen e-Ibáñez de Mendoza I, Agui e-U iza JM,
Mosqueda-Taylo A. Capsaicin in ake and o al ca cinogenesis: A sys em-
a ic e iew. Med O al Pa ol O al Ci Bucal. 2021 Ma 1;26 (2):e261-8.
A icle Numbe :24570 h p://www.medicinao al.com/
© Medicina O al S. L. C.I.F. B 96689336 - pISSN 1698-4447 - eISSN: 1698-6946
eMail: [email p o ec ed]
Indexed in:
Science Ci a ion Index Expanded
Jou nal Ci a ion Repo s
Index Medicus, MEDLINE, PubMed
Scopus, Embase and Emca e
Indice Médico Español
In oduc ion
Peppe s, chilis o Capsicum a e e sa ile c ops included
in mos daily die s, especially in some geog aphical a -
eas like China, Mexico, Tu key and Indonesia (1). Cap-
sicum plan s a e opic c ops ha g ow be e in ho e
zones and chili peppe s a e he pungen ui s o a ious
species o he Capsicum genus and membe s o he So-
lanaceae amily (2).
Chili is he mos hea ily and equen ly consumed
spice, as a la ou ing o colou ing agen , and i is also
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Med O al Pa ol O al Ci Bucal. 2021 Ma 1;26 (2):e261-8. Capsaicin in ake and o al ca cinogenesis
e ences. Ea ing chili peppe s is a cul u al adi ion in
Mexico and one o he mos consumed oods included
in hei die . In addi ion, Mexico holds one o he la g-
es annual p oduc ion (3.28 MT) and consump ion (2.33
MT) o chili peppe (22); he e o e, a high consump ion
o chili may be ela ed o a low incidence o o al cance .
The objec i e o his sys ema ic e iew is o explo e i
he e is e idence o a possible ela ionship be ween cap-
saicin in ake and he incidence o o al squamous cell
ca cinoma, and discuss such associa ion.
Ma e ial and Me hods
- In o ma ion sou ces and sea ch s a egy
The design o his s udy ul ils he PRISMA guidelines
(23). We pe o med a sys ema ic bibliog aphic esea ch
in PubMed (US Na ional Galle y o Medicine), Web o
Science and Scopus da abases, whose s a egy consis -
ed o di e en combina ions o he ollowing keywo ds:
capsaicin, chili, capsazepine, “o al cance ,” “o al ca ci-
noma", "o al squamous cell ca cinoma” and oscc (cap-
saicin AND "o al cance ”; capsaicin AND "o al ca ci-
noma"; capsaicin AND "o al squamous cell ca cinoma";
capsaicin AND oscc; chili AND "o al cance ”; chili
AND "o al ca cinoma"; chili AND "o al squamous cell
ca cinoma"; chili AND oscc; capsazepine AND "o al
cance ”; capsazepine AND "o al ca cinoma"; capsaze-
pine AND "o al squamous cell ca cinoma"; capsazepine
AND oscc). All e e enced a icles we e also sc eened
o u he manual inclusion. This e iew was no egis-
e ed a any pla o m o sys ema ic e iew.
- Inclusion and exclusion c i e ia
Using PICOs c i e ia (Table 1), in his e iew we add ess
he ela ionship be ween capsaicin in ake and o al ca ci-
nogenesis. PICO ques ion was: o al cance (popula ion),
ea men wi h capsaicin o analogues (in e en ion),
o al cance wi hou exposu e o capsaicin o analogues
(compa ison), o assess he e ec o capsaicin in he de el-
opmen o o al squamous cell ca cinoma (ou come) (23).
The inclusion c i e ia o he a icles we e: 1) s udies
published up o Ap il 2020, 2) s udies w i en in English
o Spanish, and 3) expe imen al s udies (in i o and in
i o). Meanwhile, exclusion c i e ia we e: 1) p e ious
e iews, 2) s udies ha did no in es iga e he o al ca -
cinogenesis, and 3) s udies ha did no use capsaicin as
he apeu ic agen .
- S udy selec ion and da a ex ac ion
The bibliog aphic esea ch was pe o med by wo inde-
penden e iewe s (AMS and ILIM). All i les and ab-
s ac s ha me he sea ch c i e ia we e ed and hen, he
po en ially eligible a icles we e analysed o hei inclu-
sion. Any disag eemen be ween hem was sol ed by a
hi d and ou h e iewe (AMT o JMAU) o minimize
bias o inclusion. Da a om he included s udies was
collec ed by wo e iewe s (AMS and ILIM) and c oss-
checked by ano he (AMT o JMAU) o gua an ee in eg-
a majo sou ce o p o- i amin A (ca o ene), i amin E
(α- ocophe ol) and i amin C (asco bic acid) (3). Ma-
u e peppe ui s a e ich in ca o enoids wi h an ioxi-
dan p ope ies and ha e high con en s o phenolics,
especially la onoids; in addi ion, he e a e epo s ha
men ion ha hey ha e an ioxidan and o he bioac i e
p ope ies, as well as many essen ial nu ien s such as
capsaicinoids (4-5). Capsaicinoids comp ise a dis inc-
i e g oup o molecules in ui s and plan s, which dis-
play po en ially aluable pha macological and bioac i e
p ope ies (6). Capsaicin ( ans-8-me hyl-N- anillyl-
6-nonenamide) is he main capsaicinoid ound in chili
peppe s (7).
In addi ion o i s use as a majo spice and ood addi-
i e, capsaicinoids ha e also been used o medical and
he apeu ic easons (8-9). I has been demons a ed
ha capsaicin also ac s as a cance -supp essing agen
h ough i s an ioxidan and an i-in lamma o y e ec s,
by blocking se e al signal ansduc ion pa hways, in-
cluding N -kB and AP-1 (10-11).
Cance is a majo global public heal h p oblem; acco d-
ing o Wo ld Heal h O ganiza ion (WHO) i is he second
leading cause o dea h globally (12). The associa ion be-
ween poo nu i ion and cance is inc easingly e iden ,
and ollowing a heal hy die is a key li es yle change o
educe i s ole as a cance isk ac o . The e o e, in e -
en ions o educe smoking, imp o e die and inc ease
physical ac i i y mus become much highe p io i ies in
he gene al popula ion’s heal h and heal h ca e sys ems
(13). Fu he mo e, he in ake o speci ic oods like o-
ma oes, ci ic ui s, oli e oil, be ies, honey, ea, aloe
e a o cu cuma con ain ac i e componen s ha can in-
luence he ini ia ion and p og ession o ca cinogenesis,
and could ac a ou ably on pa hways implied in cell
p oli e a ion, apop osis and me as asis (14-16).
O al squamous cell ca cinoma (OSCC) is one o he
mos p e alen cance wo ldwide (incidence a e: 4 pe
100.000 wo ldwide), and accoun s o 90% o all ma-
lignancies o he o al ca i y (17). Main isk ac o s o
OSCC a e obacco and alcohol consump ion, human
papilloma i us in ec ion and p esence o o al po en ial-
ly malignan diso de s (18). Mo eo e , al hough ea -
men s ha e imp o ed o e he yea s, p ognosis o o al
cance is s ill poo (19).
I is no ewo hy ha in coun ies whe e popula ions o
di e se e hnic g oups co-exis , di e ences ha e been
obse ed in e ms o incidence o o al cance (20). In
his ega d, when compa ing be ween coun ies, he in-
cidence a e o o al cance in Mexico is 1.5, while in
he USA i is much highe [4.3] (21), simila o wha has
been ound when classi ying by ace and e hnici y in he
la e , whe e he a e o new cases o o al cance is lowe
in Hispanics [4.62], including Mexicans, as compa ed
o whi e people [9.53] (22). Die could be conside ed as
a possible ac o o explain, a leas pa ly, hese di -
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Med O al Pa ol O al Ci Bucal. 2021 Ma 1;26 (2):e261-8. Capsaicin in ake and o al ca cinogenesis
pe o mance c i e ia we e no epo ed by he au ho s;
howe e , hese i ems we e no ele an and did no mod-
i y he o e all isk o bias assessmen .
Resul s
- Bibliog aphical esea ch
We iden i ied 98 eco ds in he ini ial da abase sea ch,
ou o which 73 we e elimina ed because we e dupli-
ca es. A e he i s sc eening, ano he 4 eco ds we e
excluded because hey did no s udy o al squamous cell
ca cinoma and 5 mo e because hey did no in es iga e
abou capsaicin. Thus, only 16 eco ds we e eligible
o analysis; o hese, 5 p e ious e iews we e also e-
mo ed, as well as 2 o he s udies ha did no use cap-
saicin as he apeu ic agen , and 3 ha did no s udy he
ole o capsaicin in o al ca cinogenesis. A he end, we
added 1 a icle h ough manual esea ch lea ing he i-
nal numbe in 7 s udies selec ed o he sys ema ic e-
iew (6,25-30). Main da a o he s udies a e shown in
Table 2. The lowcha o he selec ion p ocess is p e-
sen ed in Fig. 1.
i y o con en s.
The in o ma ion ex ac ed om each s udy was: he au-
ho and yea o publica ion, ype o o al squamous cell
ca cinoma model (cell line and animal), numbe o cases,
ype o capsaicin in ake, e ec o capsaicin in ake on o al
ca cinogenesis (incidence o epi helial dysplasia and o al
cance , epi helial-mesenchymal ansi ion, cell p oli e a-
ion, cell in asi eness, cell mig a ion, apop osis, chemo-
p e en ion, e c.).
- Risk o bias and quali y assessmen o he s udies
OHAT Risk-o bias ool was used, o bo h in i o and in
i o s udies, o e alua e hei me hodological quali y (24).
OHAT isk o -bias a ing is an e ec i e app oach ha
e alua es 11 di e en domains and 5 ypes o bias (selec-
ion, pe o mance, a i ion/ exclusion, de ec ion and se-
lec i e epo ing). The sys em o answe ing each ques-
ion equi es e iewe s o choose be ween de ini ely low/
p obably low/ p obably high/ de ini ely high isk o bias.
In gene al, he me hodological quali y o he s udies
was good, and OHAT ool showed ha isk o bias was
p obably low (24). Some ques ions o he selec ion and
Table 1: PICO c i e ia (pa icipan s/popula ion, in e en ions, compa isons, ou comes, s udy design).
Table 2: Main da a o he included s udies.
Au ho s and yea OSCC model Capsaicin/ Capsazepine/ Analogues
Tanaka e al. 2002 in i o (4-weeks old F344 male a s, 4‐NQO) capsaicin (500 ppm): 1 and 18 weeks
Ip e al. 2010 in i o (SCC-4 cell line) capsaicin (150, 200, 250, 300, 350 µM): 12, 24,
36, 48 h
Gonzales e al. 2014 in i o (SCC4, SCC25, HSC3 cell line); in i o
(A hymic nude mice, HSC3, SCC4, SCC25 cells)
in i o: CPZ (30μM), capsaicin (150 μM) 24h;
in i o: CPZ (1 μg/μl) 24h
De la Chapa e al. 2019a in i o (Cal-27, SCC-4, SCC-9 cell lines); in i o
(Sp ague-Dawley a s, Cal-27 cells)
in i o: CIDD-99 (1–10μM), CIDD-111
(2.5–40μM), CIDD-24 (20–30μM), CIDD-99
(1–7.5μM); in i o: CPZ, CIDD-24, CIDD-111
(120μg), CIDD-99 (120, 240μg)
De la Chapa e al. 2019b in i o (HSC-3 cell line) CPZ analogue 17 (20 µM), 29 (2µM): 24h
Kama uddin e al. 2019 in i o (ORL-48 cell line) capsaicin (50, 100, 150, 200, 250, 300, 350
µM): 24, 48, 72 h
Mohammed and AlQa ni,
2019 in i o (Golden Sy ian hams e s, DMBA) capsaicin (10 ppm)
4-NQO: 4-Ni oquinoline 1-oxide; CPZ: capsazepine; DMBA: 7,12-dime hylbenz(a)an h acene; OSCC: o al squamous cell ca cinoma.
Pa ame e Inclusion c i e ia Exclusion c i e ia
Popula ion S udies published un il Ap il 2020, s udies w i en
in English o Spanish, expe imen al s udies (in i o
and in i o) and clinical ials
P e ious e iews, s udies ha didn’ in es iga e
he o al ca cinogenesis, s udies ha don’ use
capsaicin as he apeu ic agen , pe sonal opinions,
p o ocol le e s, pos e s, con e ence abs ac s
In e en ion in i o and in i o models o OSCC wi h capsaicin
(o analogues) in ake
Compa ison in i o and in i o models o OSCC wi h capsaicin
(o analogues) in ake
in i o and in i o models o OSCC wi h in ake
o o he d ugs
Ou come
Find he associa ion be ween he in ake o capsa-
icin, and i s analogues, in o al ca cinogenesis
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- Indi idual s udies
Th ee o he 7 s udies included in ou analysis we e in
i o (25,28-29), 2 in i o (6,30) and 2 bo h in i o and
in i o (26-27).
In i o s udies
Ip e al. (25) we e he i s o s udy whe he di e en
doses o capsaicin could induce apop osis in ongue
cance cells. They obse ed ha 300 µM capsaicin de-
c eased he le els o mi ochond ial memb ane po en ial
(calcium in lux) and inc eased he eac i e oxygen spe-
cies (ROS). An inc ease o AIF, cy och ome c, ac i e-
caspase-9, Bax, CHOP, Fas and ac i e-caspase-8, and a
dec ease o p o-caspase-3 and Bid was also seen, all o
which led o apop osis. In addi ion, 350 µM capsaicin
also dec eased he pe cen age o iable cells, due o a -
es o cell cycle a G0/G1 s age (dose-dependen ); and
400 µM capsaicin induced DNA condensa ion, damage
and agmen a ion.
De la Chapa e al. (28) de eloped po en analogues based
upon capsazepine (CPZ) pha macopho e and s uc u e-
ac i i y ela ionships (SAR) ac oss analogues. Two o
hese, a di e en doses, had signi ican an i-p oli e a-
i e e ec s in o al cance cells.
Kama uddin e al. (29) also in es iga ed he apop o ic
e ec o capsaicin on human o al cance cells. They
saw ha inc easing concen a ions o capsaicin we e
mo e cy o oxic o malignan cells. Capsaicin-induced
apop osis occu ed h ough he shi in cell popula ion
om ea ly apop osis (24 h) o la e apop osis (48 and 72
h). I also inc eased he ac i i y o caspase-3-7-9 and
mi ochond ial memb ane po en ial. The e o e, a lowe
pe cen age o iable malignan cells was seen in capsa-
icin ea ed cells a e G1-phase, in compa ison o con-
ol cells. These esul s indica ed ha cell cycle a es o
capsaicin- ea ed cells is associa ed wi h he an ip oli -
e a i e e ec in a ime-dependen manne .
In i o s udies
The e ec s o die a y adminis a ion o o al capsaicin
on an animal ongue cance model was i s ly in es i-
ga ed by Tanaka e al. (6). These au ho s demons a ed
a lowe incidence o o al epi helial dysplasia (OED) and
ca cinoma in capsaicin- ea ed a s. Apop o ic index
(ssDNA) was highe in he capsaicin g oup, while p o-
li e a i e index (PCNA) was lowe .
Fig. 1: PRISMA lowcha . Syn hesis o he bibliog aphical analysis.
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Med O al Pa ol O al Ci Bucal. 2021 Ma 1;26 (2):e261-8. Capsaicin in ake and o al ca cinogenesis
Mohammed and AlQa ni (30) also in es iga ed he an i-
p oli e a i e e ec o capsaicin in OED and ca cinogen-
esis. Capsaicin ea ed animals had a lowe incidence
and se e i y o OED (lowe immunoexp ession o Bcl-2).
In i o and in i o s udies
Gonzales e al. (26) es ed di e se cell lines wi h di -
e en doses o CPZ and capsaicin. An 80% educ ion
in cell iabili y was obse ed wi h CPZ and capsaicin
oge he . Capsazepine also induced apop o ic ac i i y
(accumula ion o subG1 cells, inc ease o ROS and c-
PARP) o all OSCC cell lines, e en a low doses (30
μM). Howe e , his e ec changed among cell lines,
wi h mo e HSC3 and SCC25 cells in apop osis (30 μM)
o cell dea h (60 μM), han SCC4 cells a he same con-
cen a ions. These au ho s (26) also ca ied ou an in
i o expe imen wi h mice, and hey ound ha CPZ
ea ed HSC3 umou s did no enla ge as much as con-
ol g oup, and d ama ically sh ank in size, simila o
SCC25 umou s, which displayed a ma ked educ ion in
umou olume ollowing ea men wi h CPZ (50.5%).
In con as , SCC4 con ol xenog a umou s g ew nea -
ly wo- old g ea e han CPZ ea ed cases, and showed
mo e apop o ic igu es.
De la Chapa e al. (27) demons a ed he apop o ic e -
ec o bo h CPZ and CPZ analogs on a ious malignan
cells by means o S-phase block, mi ochond ial dys-
unc ion and ROS-media ed c-PARP inc ease. CIDD-
99 (500 μM) also caused an an i-p oli e a i e e ec
agains Cal-27 cells when used wi h cispla in, ge i inib,
and adia ion. The e icacy o hese analogues was also
assessed in i o, all o which educed umou olume.
Fu he mo e, in analog CIDD-99 ea ed a s, he e
we e e en no umou cells emaining in some cases.
Discussion
O al ca cinogenesis in ol es a se ies o s eps which a e
con olled by many ac o s, including gene ic, me abol-
ic and en i onmen al ones. Abou 30-35% o ca cino-
mas a e ini ia ed due o die a y ac o s (31); howe e ,
many ypes o compounds ha e also been s udied as
chemop e en i e agen s.
The link be ween capsaicin and cance has long been
s udied (32). Ini ial in es iga ions sugges ed ha con-
inuous in ake o capsaicin inc eased he isk o de elop
some ca cinomas o he diges i e ac , including gas-
ic cance . Howe e , i was la e disco e ed ha cap-
saicin migh ac , in ac , as a chemop e en i e agen ,
al e ing he mic osomal unc ion o se e al enzymes,
which a e key o he me abolic ac i a ion and de oxi i-
ca ion o mul iple mu agens.
The i s au ho s who epo ed he an ica cinogenic
p ope ies o capsaicin we e Modly e al. (33), who in-
dica ed ha his subs ance inhibi ed he me abolism o
many polycyclic a oma ic hyd oca bons like benzo(a)
py ene 3 and supp essed hei binding o human DNA.
Many s udies ha e p o en ha his e ec is ob ained
h ough he modula ion o cy och ome P450 and
NADPH dependen ac i i ies (34).
New disco e ies ha e been made in he las yea s e-
ga ding he an ip oli e a i e and apop o ic e ec o cap-
saicin on human colon and oesophageal ca cinoma (35).
I has been demons a ed ha capsaicin sup esses bo h
in insic and ex insic umou signalling pa hways,
which a e necessa y o he in asion and mig a ion o
malignan cells (36).
I is o g ea in e es o know he speci ic e ec o his
compound on ca cinomas o he uppe ae odiges i e
ac . P e ious s udies (37-38) ha e p o en ha cap-
saicin sup esses he g ow h o gas ic cance h ough
down egula ion o se e al pa hways (NADPH, ERK
1/2, p38 MAPK, JNK), inhibi ion o in lamma o y
molecules (IL-6) and inc ease o apop o ic molecules
(caspase-3, p53). On he o he hand, capsaicin also in-
duces G1 a es and apop osis o nasopha yngeal cance
cells h ough mi ochond ial depola iza ion and ac ing
on speci ic pa hways (PI3K/mTOR) and molecules (cas-
pase-3, Bcl-2) (39). In addi ion, i e ains he in asion
and mig a ion o malignan oesophagus cells by inhibi-
ion o MAPK signalling pa hway, in acellula s ess
and p omo ion o p53 (40).
The eason behind his e iew was o acknowledge he
link be ween capsaicin and o al cance (8). P e ious
s udies showed molecula e idences o o al cell p oli -
e a ion inhibi ion associa ed o o he compounds, such
as lycopene, g een ea polyphenols, es e a ol and cu -
cumin (41). Apop osis o o al malignan cells has also
been ela ed o lycopene, que ce in, epigalloca equin
galla e, hea la in-3 galla e, ga lic and ginge (42-43).
Acco ding o ou sea ch, all he s udies included in his
e iew (6,25-30) con i m ha capsaicin mus be consid-
e ed as a chemop e en i e agen o o al cance (Fig.
2) check Supplemen 1 (h p://www.medicinao al.com/
medo al ee01/aop/24570_supplemen 1.pd ). Since he
o iginal epo , i was sugges ed ha con inuous in ake
o capsaicin dec eased he incidence o o al cance , be-
cause i s opped he p oli e a i e ac i i y o malignan
cells and inc eased hei apop osis (6). Mo eo e , di e -
en s udies ha e obse ed a educ ion on umou size in
mice ea ed wi h CPZ (26), and e en absence o malig-
nan cells in a s ea ed wi h CPZ (27).
This cy o oxic e ec o capsaicin has been demons a ed
and ein o ced wi h di e en echniques h oughou he
yea s, and i seems o be ime and dose dependen ; how-
e e , since low doses o capsaicin con inue o be chemo-
p e en i e, mul iple in i o s udies ha e been ca ied
ou in o de o unco e i s molecula mechanisms. Ip e
al. (25) poin ed ou ha capsaicin induces G0/G1 cell
cycle a es and apop osis in SCC-4 cells, h ough an
inc ease o ROS, Ca2+ and caspase-9. Also, i p oduces
he o e exp ession o se e al molecules o cellula s ess
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ha lead o apop osis (AIF, cy och ome c, Bax, CHOP,
Fas). The same apop o ic pa hway was obse ed by
Kama uddin e al. (29), wi h less iable cells a e G1-
phase in he capsaicin ea ed g oup, due o an inc ease
o caspases and mi ochond ial depola iza ion, and also
simila esul s we e ound by de la Chapa e al. (27),
who epo ed an inc ease o ROS-media ed c-PARP.
I is no ewo hy ha , in spi e o using di e en cell
lines, capsaicin doses and du a ion o ea men s, bo h
capsaicin and CPZ igge he same al e a ions on he
malignan cells. We conside ha hese esul s indica e
ha he an ip oli e a i e e ec o capsaicin could be
linked o apop osis. In e es ingly, some s udies showed
ha CPZ has a s onge cy o oxic ac i i y han capsa-
icin, since mo e cells unde wen apop osis and showed
pheno ypic changes (26). Fu he mo e, CPZ wi hou
capsaicin also dec eases cell p oli e a ion and umou
size, and e en p omo es he e ec o chemo and adio-
he apy (27-28).
Ano he aspec o g ea in e es is he link be ween cap-
saicin and OED (6,30). To da e, his opa hological analy-
sis is he gold s anda d echnique o make a diagnosis o
o al cance , while p esence o OED ep esen s he key
p ognos ic ac o o p edic malignan ans o ma ion
o a lesion in he o al mucosa; hus, i s ecogni ion and
g adua ion is e y impo an o p ima y and second-
a y p e en ion o o al cance . In his sense, Tanaka e
al.(6) ound ha capsaicin- ea ed animals had a lowe
incidence o OED, which la e Mohammed and AlQa ni
(30) p o ed o be ela ed o a lowe immunoexp esion o
an i-apop o ic bioma ke Bcl-2.
Conside ing all he a ailable in o ma ion, we belie e
die a y consump ion o capsaicin could p o ide a che-
mop e en i e e ec o o al squamous cell ca cinoma.
We hink his p o ec i e p ope y may explain why he
incidence o o al cance upon chili consume s is lowe .
In ac , peppe s co e 1.93 million ha o c op-g owing
su ace a eas wo ldwide, and Mexico is he second la g-
es peppe p oduce in he wo ld (2.3 million) (1). Thus,
in ake o capsaicin is an impo an sociocul u al ele-
men in some popula ions. Al hough indi ec ly, he e is
epidemiological e idence sugges ing ha he p o ec i e
e ec o capsaicin could be esponsible, a leas pa ial-
ly, o he dispa i ies obse ed in he incidence o o al
cance among di e en e hnic g oups li ing in he same
popula ion, such as he USA, whe e he a e o new cas-
es o o al cance is signi ican ly lowe in Hispanics han
in whi e people (21) (Fig. 3).
Ne e heless, mo e s udies a e needed o u he un-
de s and he mechanism by which hese compounds
p e en o al ca cinogenesis, and o de elop no el he a-
peu ic agen s o clinical applica ion agains o al cance .
Conclusions
In summa y, his s udy gi es a comp ehensi e iew o
he ela ionship be ween capsaicin and o al ca cinogen-
esis. Bo h capsaicin and capsazepine a e chili subs anc-
es ha may p e en he de elopmen o o al epi helial
dysplasia and o al squamous cell ca cinoma. The s eps
in which hese compounds could ha e a chemop e en-
i e ac i i y agains o al cance a e: inhibi ion o ma-
lignan cell p oli e a ion and inc ease o malignan cell
apop osis. These indings elucida e why die a y in ake
o capsaicin could explain he exis ing di e ences in
he p e alence o OSCC in ce ain wo ld popula ions.
Fu u e esea ch should ocus on humans, o in es iga e
he ela ionship be ween consump ion o speci ic oods
such as chili (capsaicin) and he p e alence o o al can-
ce , h ough well-designed s udies (pa ien -clinician
communica ion, ood equency ques ionnai es, e c.).
Fig. 2: O al ca cinogenesis p ocesses in which capsaicin/capsazepine/analogues may be implica ed.
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Acknowledgemen s
This esea ch was no suppo ed by any speci ic agency in he public,
comme cial, o no - o -p o i sec o s.
Funding
None decla ed.
Con lic o in e es
None decla ed.
Au ho s con ibu ions
And ea Mosqueda-Solís and I ene La uen e-Ibáñez de Mendoza
ha e an equal con ibu ion.
