capsaicin and red chili pepper-benefits or side effects
RED CHILI PEPPER BENEFITS- FIGHT AGAINST CANCER?

In a recent study, researchers found that red chili pepper appear to be effective inhibitors of the cancer
process. They looked at the chemotherapeutic potential of capsaicin, the "hot" ingredient in red chili pepper
that is often associated with antioxidative and anti-inflammatory activities. In the study, it exhibited anticancer
activity against pancreatic cancer cells. It disrupted the mitochondrial function resulting in the release of
cytochrome c, which induced apoptosis, or programmed cell death, in the cancerous cells without affecting
normal pancreatic cells.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the main pungent principle of hot pepper, which is
consumed in high quantities by humans worldwide. The capsaicin content of some chili varieties ranges up to
0.53%. [2] Some people believe that red pepper /capsaicin provides multiple health benefits for various
chronic  inflammatory diseases such as cancer, atherosclerosis, myocardial infarction, diabetes, allergy,
asthma, arthritis, Crohn's disease, multiple sclerosis, Alzheimer's disease, osteoporosis, psoriasis, septic
shock, and AIDS. It is because these chronic inflammatory diseases are associated with the activation of
nuclear transcription factor kappaB. While, capsaicin derived from red pepper has been shown to be able to
interrupt the pathway activating this transcription factor. [1,6,7,10,14, 16]

RESEARCH FINDINGS
I. Capsaicin causes inhibition of the activity of the transcription factors AP-1 and NF-kappaB, thus inhibiting
cell proliferation and enhancing apoptosis. [3]

II. Capsaicin targets tNOX, a tumor (cancer)-specific surface hydroquinone (NADH) oxidase with protein
disulfide-thiol interchange activity (ECTO-NOX protein). Accordingly vector-forced over expression of tNOX in
MCF-10A mammary epithelia or COS cells that lack tNOX or in COS cells that underexpress tNOX enhanced
the susceptibility of growth and apoptosis to capsaicin. Additionally, the tNOX-transfected MCF-10A cells
proliferated in Matrigel, a measure of invasiveness. In contrast, oligomeric antisense tNOX DNA abrogated
growth inhibition by capsaicin and reduced anchorage-dependent growth of HeLa (human cervical carcinoma)
cells that naturally overexpress tNOX.

The findings show cell surface expression of tNOX as both necessary and sufficient for the cellular anticancer
activities attributed to capsaicin. [4]

III. Capsaicin induced apoptotic MBT-2 murine bladder tumor cell death in a time- and dose-dependent
manner. In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in
Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of
inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying
that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. [5]

IV Capsaicin selectively induces apoptosis in H-ras-transformed MCF10A human breast epithelial cells but not
in their normal cell counterparts. [8]

V. Treatment with capsaicin or the PPARgamma ligand troglitazone induced apoptotic cell death in a
dose-dependent manner in HT-29 human colon cancer cells. Thus, capsaicin-induced apoptotic cell death in
HT-29 human colon cancer cells could be associated with the Peroxisome proliferator-activated receptor
gamma pathway without the involvement of the vanilloid receptor. [9]

VI Capsaicin suppressed the growth of leukemic cells, but not normal bone marrow mononuclear cells, via
induction of G(0)-G(1) phase cell cycle arrest and apoptosis. Capsaicin-induced apoptosis was in association
with the elevation of intracellular reactive oxygen species production. Interestingly, capsaicin-sensitive
leukemic cells were possessed of wild-type p53, resulting in the phosphorylation of p53 at the Ser-15 residue
by the treatment of capsaicin. Abrogation of p53 expression by the antisense oligonucleotides significantly
attenuated capsaicin-induced cell cycle arrest and apoptosis. Pretreatment with the antioxidant
N-acetyl-L-cystein and catalase, but not superoxide dismutase, completely inhibited capsaicin-induced
apoptosis by inhibiting phosphorylation of Ser-15 residue of p53. Moreover, capsaicin effectively inhibited
tumor growth and induced apoptosis in vivo using NOD/SCID mice with no toxic effects.  [11]

VII Studies have demonstrated that capsaicin induces apoptotic cell death in human gastric cancer cells
(SNU-1) in vitro which may be possibly mediated by the overexpression of p53 and/or c-myc genes. [21]

RED CHILI PEPPER (CAPSAICIN) PROMOTING CANCER? -- SIDE EFFECTS?
Most findings discussed in the last section were done in either test-tube or animal studies only. Now, we  move
on to see what impact of red chili pepper or capsaicin onthe human health.

OBSERVATION I-GASTRIC CANCER IN MEXICO
Gastric cancer incidence was high in Mexico. A population-based case-control study was conducted in Mexico
City during 1989-1990 to evaluate the relation between chili pepper consumption and gastric cancer risk. The
study included 220 incident cases and 752 controls randomly selected from the general population.
Information was collected by interview. Chili pepper consumers were at high risk for gastric cancer compared
with non-consumers. [17]

A few years later, researchers from Mexico National Institute of Public Health conducted a survey to check if
the intake of capsaicin (chili peppers) increases the risk of gastric cancer again. They studied 234 cases of
gastric cancer and 468 matched controls in three areas of Mexico from 1994-1996. They acquired information
about chili pepper intake and determined the capsaicin amount by gas chromatography for each individual;
they concluded that the risk of gastric cancer was linked to high consumption of capsaicin. [12]

OBSERVATION II-GASTRIC AND LIVER CANCERS IN FOUR SUB-POPULATIONS
There are four cookeries in the United States have high pepper content: Mexican-American, Cajun, white
Creole, and black Creole. Each is largely confined to a single ethnic-cultural group which is concentrated in
some counties. Researchers from the University of Utah found that significantly higher rates for stomach and
liver cancer in counties inhabited by these four ethnic-cultural groups than in matched control counties. From
statistical analysis, they conclude that the odds ratio was above 5 for the stomach cancer association with
capsaicin pepper. [15]

OBSERVATION III-ESOPHAGEAL CANCER IN NORTHEN IRAN
Cancer of the esophagus has a more varied geographical distribution and incidence than any other commonly
occurring cancer. In the high-risk region of northern Iran, where the frequency of esophageal cancer is higher
among women than men, the main food during pregnancy contains strong black pepper and sharp crushed
pomegranate seeds, which irritate the esophagus. [18]

Researchers from Sungkyunkwan University, Korea, proposed that capsaicin altered the metabolism of
chemical carcinogens and may promote carcinogenesis at high doses. [13]

OBSERVATION IV-STOMACH CANCER IN TRIVANDRUM, INDIA
Researchers conducted a prospective case-control study of 194 patients suffered from stomach cancer
during the period 1988-1991 in Trivandrum, India. They collected information such as
socio-demographic/economic background, tobacco chewing, tobacco smoking and alcohol habits from the
patients and controls. They analyzed the data using a multiple logistic regression model, and they concluded
that increased risks were associated with higher consumption of chili. [19]

OBSERVATION IV-GALLBLADDER CANCER IN INDIA
Cancer of the gallbladder is rare but fatal, and has an unusual geographic and demographic distribution.
Gallstones and obesity have been suggested as possible risk factors. Researchers conducted a case-control
study of 165 diagnosed cases of gallstones or gallbladder cancer. The researchers evaluated their dietary
habits and they found an increase in the odds with consumption of capsicum (OR 2.2), beef (OR 2.58), tea
(OR 1.98), red chilli (OR 1.29) and mutton (OR 1.2). [20]

SCIENTIFIC SUPPORTS
There are actually a few experiments supporting the view that a large consumption of capsicum or hot pepper
chili is linked to cancer. Mexican researchers dosed mouse with capsaicin at 1.46 and 1.94 mg/kg via i.p. route
for 32 days. Based on the frequency of micronucleated normochromatic erythrocytes, the researchers
detected the genotoxic response at dose of 1.94 mg/kg appeared on day 16 and that at dose of 1.46 mg/kg
on day 32. While, based on sister chromatid exchanges frequency, they detected the genotoxic response only
with the higher dose. These results suggest that excessive consumption of capsicum (hot pepper chili) is
linked to gastric cancer. [22] In another study, researchers administered 6 weeks old Swiss mice with
capsaicin in a semisynthetic powdered diet at 0.03125% level. They observed that 22% of females and 14% of
males developed cecum tumors while only 8% incidences happened in the controls. [23]

CONCLUSION
It is not sure if  capsaicin is carcinogenic or anti-cancer. But, there are some indications that large
consumption of hot pepper chili is linked to stomach cancers.

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phytochemicals: reasoning for seasoning. Ann N Y Acad Sci. 2004 Dec;1030:434-41. [2] Toth B and Gannett P,
Carcinogenicity of lifelong administration of capsaicin of hot pepper in mice. In Vivo. 1992 Jan-Feb;6(1):59-63. [3] Shimizu
M and Weinstein IB Modulation of signal transduction by tea catechins and related phytochemicals. Mutat Res. 2005 Jun
28. [4] Chueh PJ et al, tNOX is both necessary and sufficient as a cellular target for the anticancer actions of capsaicin and
the green tea catechin (-)-epigallocatechin-3-gallate. Biofactors. 2004;20(4):235-49. [5] Lee JS et al, Capsaicin-induced
apoptosis and reduced release of reactive oxygen species in MBT-2 murine bladder tumor cells. Arch Pharm Res. 2004
Nov;27(11):1147-53. [6] Dorai T and Aggarwal BB Rol e of chemopreventive agents in cancer therapy. Cancer Lett. 2004
Nov 25;215(2):129-40. [7] Aggarwal BB, Takada Y and Oommen OV. From chemoprevention to chemotherapy: common
targets and common goals. Expert Opin Investig Drugs. 2004 Oct;13(10):1327-38. [8] Kim S and Moon A
Capsaicin-induced apoptosis of H-ras-transformed human breast epithelial cells is Rac-dependent via ROS generation. Arch
Pharm Res. 2004 Aug;27(8):845-9. [9] Kim CS et al, Capsaicin, a spicy component of hot pepper, induces apoptosis by
activation of the peroxisome proliferator-activated receptor gamma in HT-29 human colon cancer cells. J Med Food. 2004
Fall;7(3):267-73. [10] Lee YS et al, Involvement of NADPH oxidase-mediated generation of reactive oxygen species in the
apototic cell death by capsaicin in HepG2 human hepatoma cells. Free Radic Res. 2004 Apr;38(4):405-12. [11] Ito K et al,
Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of
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Lopez-Carrillo L et al, Capsaicin consumption, Helicobacter pylori positivity and gastric cancer in Mexico. Int J Cancer. 2003
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Jones DW, Capsaicin pepper, cancer and ethnicity Med Hypotheses. 2002 Oct;59(4):450-7. [16] Teel RW and Huynh HT
Lack of the inhibitory effect of intragastrically administered capsaicin on NNK-induced lung tumor formation in the A.J
mouse. In Vivo. 1999 May-Jun;13(3):231-4. [17] Lopez-Carrillo L et al, Chili pepper consumption and gastric cancer in
Mexico: a case-control study. Am J Epidemiol. 1994 Feb 1;139(3):263-71. [18] Ghadirian P et al, Food habits and
esophageal cancer: an overview. Cancer Detect Prev. 1992;16(3):163-8. [19] Mathew A et al, Diet and stomach cancer: a
case-control study in South India. Eur J Cancer Prev. 2000 Apr;9(2):89-97. [20] Pandey M and Shukla VK, Diet and
gallbladder cancer: a case-control study. Eur J Cancer Prev. 2002 Aug;11(4):365-8. [21] Kim JD et al, Capsaicin can alter
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A few test-tube studies suggest that spices like red chili pepper, may provide a cancer-fighting benefit by
slowing or preventing the growth of cancerous tumor cells. The findings have been published in various
nationwide scientific journals.
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