Capsicum is a genus of flowering plants native to the Americas, where they have been cultivated as a food, spice, and medicine for thousands of years by the native peoples of what are now the United States, Mexico, and Central and South America. The fruit of Capsicum plants include chile peppers and bell peppers. Cayenne powder and paprika powder, made by grinding dried peppers, are used for seasoning in many cuisines.
About forty species of Capsicum are known to exist, five of which have been domesticated for agricultural production. Each species includes many varieties; for example, bell peppers and jalapenos are both varieties of Capsicum annuum. Capsaicin is the primary flavonoid in most Capsicum peppers and is what endows them with their varying degrees of hot, pungent flavors and aromas. In addition to creating a strong burning sensation in the mouth, capsaicin is an antioxidant with cancer-fighting powers and one of the primary sources of many of the health benefits of peppers.
Antioxidant and antiproliferative activities of common vegetables. Chu YF, Sun J, WuX, Liu RH. J Agric Food Chem. 2002 Nov 6;50(23):6910-6. Key Finding: “In this study, 10 common vegetables were selected on the basis of consumption per capita data in the U.S. Broccoli possessed the highest total phenolic content, followed by spinach, yellow onion, red pepper, carrot, cabbage, potato, lettuce, celery, and cucumber. Red pepper had the highest total antioxidant activity, followed by broccoli, carrot, spinach, cabbage, yellow onion, celery, potato, lettuce and cucumber. Antiproliferative activities were also studied in vitro using human liver cancer cells. Spinach showed the highest inhibitory effect, followed by cabbage, red pepper, onion, and broccoli.”
Capsaicin induces apoptosis through ubiquitin-proteasome system dysfunction. Maity R, Sharma J, Jana NR. J Cell Biochem. 2010 Apr 1;109(5):933-42. Key Finding: “Capsaicin is an active component of red pepper having an antiproliferative effect in a variety of cancer cells due to its ability to induce apoptosis. Treatment of capsaicin to mouse neuro 2a cells results in the inhibition of proteasome activity in a dose- and time-dependent manner that seems to correlate with its effect on cell death. Our results strongly support the use of capsaicin as an anticancer drug.”
In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper Nigrum) and cardamom (Elettaria cardamomum). Majdalawieh AF, Carr RI. J Med Food. 2010 Apr;13(2):371-81. Key Finding: “Our findings strongly suggest that black pepper and cardamom exert immunomodulatory roles and antitumor activities and hence they manifest themselves as natural agents that can promote the maintenance of a healthy immune system.”
Capsaicin induces apoptosis in SCC-4 human tongue cancer cells through mitochondria-dependent and—independent pathways. Ip SW, Lan SH, Huang AC, Et al. Environ Toxicol. 2010 Oct 5 (Epub ahead of print). Key Finding: “Herein, we investigated whether capsaicin induces apoptosis in human tongue cancer SCC-4 cells. Capsaicin decreased the percentage of viable cells in a dose-dependent manner and produced DNA fragmentation and GO/G1 phase arrest in SCC-4 cells.”
Apoptosis induced by capsaicin and resveratrol in colon carcinoma cells requires nitric oxide production and caspase activation. Kim MY, Trudel LJ, Wogan GN. Anticancer Res. 2009 Oct;29(10):3733-40. Key Finding: “We examined the role of nitric oxide and influence of p53 status during apoptosis induced by these agents in two isogenic HCT116 human colon carcinomas, wild-type p53 and complete knockout of p53 cells. Capsaicin and resveratrol, alone or in combination, inhibited cell growth and promoted apoptosis by the elevation of nitric oxide; combined treatment in p53-WT cells was most effective. These findings offer exciting opportunities to improve the effectiveness of colon cancer treatment.”
Capsaicin-induced apoptosis in human hepatoma HepG2 cells. Huang SP, Chen JC, Wu CC, Chen CT, Tang NY, Ho YT, Lin JP, Chung JG, Lin JG. Anticancer Res. 2009 Jan;29(1):165-74. Key Finding: “Our results indicated that the capsaicin-induced apoptosis in HepG2 cells may result from the elevation of intracellular Ca2+ production, ROS, disruption of alpha psi(m), regulation of Bcl-2 family protein expression and caspase-3 activity.”
Suppression of cFLIP by lupeol, a dietary triterpene, is sufficient to overcome resistance to TRAIL-mediated apoptosis in chemo resistant human pancreatic cancer cells. Murtaza I, Saleem M, Adhami VM, Hafeez BB, Mukhtar H. Cancer Res. 2009 Feb 1;69(3):1156-65. Key Finding: “Our findings showed the anticancer efficacy of lupeol with mechanistic rationale against highly chemo resistant human PaC cells. We suggest that lupeol, alone or as an adjuvant to current therapies, could be useful for the management of human PaC.”
Lupeol triterpene, a novel diet-based microtubule targeting agent: disrupts surviving/cFLIP activation in prostate cancer cells. Saleem M, Murtaza I, Witkowsky O, Kohl AM, Maddodi N. Biochem Biophys Res Commun. 2009 Oct 23;388(3):576-82. Key Finding: “We conclude that the Lupeol-induced growth inhibition of CaP cells is a net outcome of simultaneous effects on stathmin, cFLIP, and surviving which results in the disruption of microtubule assembly. We suggest that Lupeol alone or as an adjuvant to other microtubule agents could be developed as a potential agent for the treatment of human CaP.”
Lupeol, a novel anti-inflammatory and anti-cancer dietary triterpene. Saleem M. Cancer Lett. 2009 Nov 28;285(2):109-15. Key Finding: “Lupeol, a triterpene found in green pepper, white cabbage, olive, strawberry, mangoes and grapes, was reported to possess beneficial effects as a therapeutic and preventive agent for a range of disorders. Lupeol at its effective therapeutic doses exhibit no toxicity to normal cells and tissues. This mini review provides detailed account of preclinical studies conducted to determine the utility of lupeol as a therapeutic and chemo preventive agent for the treatment of inflammation and cancer.”
Capsaicin, a component of red peppers, induces expression of androgen receptor via PI3K and MAPK pathways in prostate LNCaP cells. Malagarie-Cazenave S, Olea-Herrero N, Vara D, Diaz-Laviada I. FEBS Lett. 2009 Jan 5;583(1):141-7. Key Finding: “In this study, capsaicin induced an increase in the cell viability of the androgen-responsive prostate cancer LNCaP cells.”
Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell lines. Yang KM, Pyo JO, Kim GY, Yu R, Han IS, Ju SA, Kim WH, Kim BS. Cell Mol Biol Lett. 2009;14(3):497-510. Key Finding: “Our results clearly showed that capsaicin induced apoptosis in colon cancer cells. Although the actual mechanisms of capsaicin-induced apoptosis remain uncertain, it may be a beneficial agent for colon cancer treatment and chemoprevention.”
Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway. Chou CC, Wu YC, Wang YF, Chou MJ, Kuo SJ, Chen DR. Oncol Rep. 2009 Mar;21(3):665-71. Key Finding: “Our results suggest that capsaicin induces cellular apoptosis (in MCF-7 breast cancer cells) through a caspase-independent pathway and that reactive oxygen species and intracellular calcium ion fluctuation has a minimal role in the process.”
A case-control study of gallbladder cancer in Hungary. Nakadaira H, Lang I, Szentirmay Z, Hitre E, Kaster M, Yamamoto M. Asian Pac J Cancer Prev. 2009;10(5):833-6. Key Finding: “Our previous study indicated an association of chili pepper consumption with gallbladder cancer in the presence of gallstones in Chile. We investigated whether or not a similar association was present in Hungary, where mortality from gallbladder cancer is high and chili peppers are frequently consumed. Hungarian hot pepper consumption was identified as a risk factor for gallbladder cancer by multivariate logistic regression analysis.”
Lupeol inhibits growth of highly aggressive human metastatic melanoma cells in vitro and in vivo by inducing apoptosis. Saleem M, Maddodi N, Abu Zaid M, Khan N, bin Hafeez B, Asim M, Suh Y, Yun JM, Setaluri V, Mukhtar H. Clin Cancer Res. 2008 Apr 1;14(7):2119-27. Key Finding: “Our findings showed the anticancer efficacy of lupeol, a triterpene, with mechanistic rationale against metastatic human melanoma cells. We suggest that lupeol, alone or as an adjuvant to current therapies, could be useful for the management of human melanoma.”
Growth inhibition of human colon cancer cells by plant compounds. Duessel S, Heuertz RM, Ezekiel UR. Clin Lab Sci. 2008 Summer;21(3):151-7. Key Finding: “The purpose of this study was to determine if resveratrol from red grapes, cinnamaldehyde from cinnamon, and piperine from black pepper has anti-proliferative effects on colon cancer. All phytochemicals displayed anti-proliferative effects on DLD-1 colon cancer cells in culture. These results taken together with everyday dietary availability of concentrations used in this study strongly suggest that regular intake of low doses of these phytochemicals offer preventive effects against colon cancer.”
Fruits, vegetables, soy foods and breast cancer in pre- and postmenopausal Korean women: a case-control study. Do MH, Lee SS, Kim JY, Jung PJ, Lee MH. Int J Vitam Nutr Res. 2007 Mar;77(2):130-41. Key Finding: “High tomato intake was associated with reduced breast cancer risk in premenopausal women. In postmenopausal women, green pepper intake showed an inverse association of breast cancer risk.”
Immunotherapy of tumors with neuroimmune ligand capsaicin. Beltran J, Ghosh AK, Basu S. J Immunol. 2007 Mar 1;178(5):3260-4. Key Finding: “In this study, we demonstrate that intratumoral administration of capsaicin into a preexisting tumor results in retarded progression of the injected tumor regardless of whether the tumor is at its early or late stage. Furthermore, it leads to significant inhibition of growth of other, uninjected tumors in the same animal. Capsaicin-elicited immunity is shown to be T cell-mediated and tumor-specific.”
Capsaicin induced apoptosis of B16-F10 melanoma cells through down-regulation of Bci-2. Jun HS, Park T, Lee CK, Kang MK, Park MS, Kang H, Surh YJ, Kim OH. Food Chem Toxicol. 2007 May;45(5):708-15. Key Finding: “These findings indicate that capsaicin from hot chili peppers induces apoptosis of B16-F10 melanoma cells via down-regulation the Bci-2.”
Apoptosis induced by capsaicin in prostate PC-3 cells involves ceramide accumulation, neutral sphingomyelinase, and JNK activation. Sanchez AM, Malagarie-Cazenave S, Olea N, Vara D, Chiloeches A, Diaz-Laviada I. Apoptosis. 2007 Nov;12(11):2013-24. Key Finding: “Numerous studies have recently focused on the anticarcinogenic, anti- mutagenic, or chemo preventive activities of the main pungent component of red pepper, capsaicin. We have previously shown that, in the androgen-independent prostate cancer PC-3 cells, capsaicin inhibits cell growth and induces apoptosis through reactive oxygen species generation. In the present study, we investigated the signaling pathways involved in the antiproliferative effect of capsaicin.”
Catechin-vanilloid synergies with potential clinical applications in cancer. Morre DM, Morre DJ. Rejuvenation Res. 2006 Spring;9(1):45-55. Key Finding: “A cancer-specific cell surface protein, tNOX, has been identified as a target for low-dose cell killing (apoptosis) of cancer cells by green tea catechins and Capsicum vanilloid combinations. This protein is uniquely associated with all forms of cancer and is absent from normal cells and tissues. Its activity is correlated with cancer growth. When blocked, cancer cells fail to enlarge after division and eventually die.”
Capsaicin induced cell cycle arrest and apoptosis in human esophagus epidermoid carcinoma CE 81T/VGH cells through the elevation of intracellular reactive oxygen species and Ca2+ productions and caspase-3 activation. Wu CC, Lin JP, Yang JS, Chou ST, Chen SC, Lin YT, Lin HL, Chung JG. Mutat Res. 2006 Oct 10;601(1-2):71-82. Key Finding: “These results suggest that the capsaicin-induced apoptosis in the CE 81T/VGH cells may result from the activation of caspase-3 and intracellular Ca2+ release pathway and it is further suggested that capsaicin has potential as a novel therapeutic agent for the treatment of esophagus epidermoid carcinoma cells.”
Biological activity of carotenoids in red paprika, Valencia orange and golden delicious apple. Molnar P, Kawase M, Satoh K, Sohara Y, Tanaka T, Tani S, Sakagami H, Nakashima H, Motohashi N, Gyemant N, Molnar J. Phytother Res. 2005 Aug;19(8):700-7. Key Finding: “Carotenoid fractions were extracted from red paprika, Valencia orange peel and the peel of Golden delicious apple. Apple showed potent anti-H. Pylori activity. The extracts were inactive against HIV. Apple and orange showed slightly higher cytotoxic activity against three human tumor cells lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG, and human promyelocytic leukemic HL-60 cells. Paprika scavenged efficiently. The data suggest the potential importance of carotenoids as possible anti-H. Pylori and multidrug resistance reversal agents.”
Bioactivities of Anastasia black (Russian sweet pepper). Shirataki Y, Kawase M, Sakagami H, Nakashima H, Tani S, Tanaka T, Sohara Y, Schelz Z, Molnar J, Motohashi N. Anticancer Res. 2005 May-Jun;25(38):1991-9. Key Finding: “Some fractions of hexane and acetone extracts of Russian sweet pepper showed higher cytotoxic activity against three human oral tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG) than against three normal human oral cells. No fractions displayed anti-HIV activity, but some hydrophobic fractions showed higher anti-H. Pylori activity.”
Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 murine bladder tumor cells. Lee JS, Chang JS, Lee JY, Kim JA. Arch Pharm Res. 2004 Nov;27(11):1147-53. Key Finding: “These results suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.”
Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Ito K, Nakazato T, Yamato K, Miyakawa Y, Yamada T, Hozumi N, Segawa K, Ikeda Y, Kizaki M. Cancer Res. 2004 Feb 1;64(3):1071-8. Key Finding: “Capsaicin effectively inhibited tumor growth and induced apoptosis in vivo using NOD/SCID mice with no toxic effects. We conclude that capsaicin has potential as a novel therapeutic agent for the treatment of leukemia.”
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. Kim CS, Park WH, Park JY, Kang JH, Kim MO, Kawada T, Yoo H, Han IS, Yu R. J Med Food. 2004 Fall;7(3):267-73. Key Finding: “Our data suggest that capsaicin-induced apoptotic cell death in HT-29 human colon cancer cells could be associated with the PPARgamma pathway without the involvement of the vanilloid receptor. Capsaicin may have a beneficial effect for the treatment of colon cancer.”
Non-pungent capsaicinoids from sweet pepper synthesis and evaluation of the chemo preventive and anticancer potential. Macho A, Lucena C, Sancho R, Daddario N, Minassi A, Munoz E, Appendino G. Eur J Nutr. 2003 Jan;42(1):2-9. Key Finding: “These results (from tumoral cells) suggest that capsiates target a variety of pathways involved in cancer development and inflammation, and have considerable potential for dietary health benefits.”
Capsaicin inhibits growth of adult T-cell leukemia cells. Zhang J, Nagasaki M, Tanaka Y, Morikawa S. Leuk Res. 2003 Mar;27(3):275-83. Key Finding: “Capsaicin treatment inhibited the growth of ATL cells both in dose and time-dependent manner. The inhibitory effect was mainly due to the induction of cell cycle arrest and apoptosis. Based on these findings, capsaicin may be considered for chemoprevention of adult T-cell leukemia.”
Synergistic Capsicum-tea mixtures with anticancer activity. Morre DJ, Morre DM. J Pharm Pharmacol. 2003 Jul;55(7):987-94. Key Finding: “We have demonstrated a synergy between a decaffeinated green tea concentrate and a vanilloid-containing Capsicum preparation. At a ratio of 25 parts green tea concentrate to 1 part Capsicum preparation, the resultant product exhibited efficacy in the killing of cancer cells in culture 100-times that of green tea on a weight basis.”
Cytotoxic and multidrug resistance reversal activity of a vegetable, Anastasia Red’, a variety of sweet pepper. Motohashi N, Wakabayashi H, Kurihara T, Takada Y, Maruyama S, Sakagami H, Nakashima H, Tani S, Shirataki Y, Kawase M, Wolfard K, Molnar J. Phytother Res. 2003 Apr;17(4):348-52. Key Finding: “These extracts showed relatively higher cytotoxic activity against two human oral tumors cell lines (HSC-2, HSG) than against normal human gingival fibroblasts, suggesting a tumor-specific cytotoxic activity.”
Antioxidant and antiproliferative activities of common vegetables. Chu YF, Sun J, WuX, Liu RH. J Agric Food Chem. 2002 Nov 6;50(23):6910-6. Key Finding: “In this study, 10 common vegetables were selected on the basis of consumption per capita data in the U.S. Broccoli possessed the highest total phenolic content, followed by spinach, yellow onion, red pepper, carrot, cabbage, potato, lettuce, celery, and cucumber. Red pepper had the highest total antioxidant activity, followed by broccoli, carrot, spinach, cabbage, yellow onion, celery, potato, lettuce and cucumber. Antiproliferative activities were also studied in vitro using human liver cancer cells. Spinach showed the highest inhibitory effect, followed by cabbage, red pepper, onion, and broccoli.”
Antimutagenic activity of carotenoids in green peppers against some nitroarenes. Gonzalez de Mejia E, Quintanar-Hernandez A, Loarca-Pina G. Mutat Res. 1998 Aug 7;416(1-2):11-9. Key Finding: “These results suggest that each one of the pepper extracts have more than one antimutagenic compound (e.g., beta- carotene and xanthophyll) and those functional nutrients apparently have a synergistic effect.”
Chemo protective effects of capsaicin and diallyl sulfide against mutagenesis or tumorigenesis by vinyl carbamate and N-nitrosodimethylamine. Surh YJ, Lee RC, Park KK, Mayne ST, Liem A, Miller JA. Carcinogenesis. 1995 Oct;16(10):2467-71. Key Finding: “The results of this study suggest that capsaicin, a major ingredient of hot chili peppers, and diallyl sulfide from garlic suppress VC and NDMA-induced mutagenesis or tumorigenesis in part through inhibition of the cytochrome P-450 IIE 1 isoform responsible for activation of these carcinogens.”
Hypoxanthine levels in human urine serve as a screening indicator for the plasma total cholesterol and low-density lipoprotein modulation activities of fermented red pepper paste. Kim Y, Park YJ, Yang SO, Et al. Nutr Res. 2010 Jul;30(7):455-61. Key Finding: “Marked cholesterol modulation was observed in the fermented red pepper paste treated group compared with the placebo group.”
Administration of tomato and paprika beverages modifies hepatic glucose and lipid metabolism in mice: a DNA microarray analysis. Aizawa K, Matsumoto T, Inakuma T, Ishijima T, Nakai Y, Abe K, Amano F. J Agric Food Chem. 2009 Nov 25;57(22):10964-71. Key Finding: “To examine whether the expression of hepatic genes, including biomarkers, is affected by the ingestion of tomato or paprika, mice were given tomato beverage, paprika beverage, or water control for 6 weeks. The ingestion of tomato or paprika un-regulated the expression of 687 and 1045 genes and down-regulated the expression of 841 and 653 genes respectively. These changes in gene expression suggest that tomato ingestion promotes flycogen accumulation and stimulates some specific steps in fatty acid oxidation. Paprika ingestion promoted the entire glucose and fatty acid metabolic pathways to improve lipid profiles.”
Effects of daily ingestion of chili on serum lipoprotein oxidation in adult men and women. Ahuja KD, Ball MJ. Br J Nutr. 2006 Aug;96(2):239-42. Key Finding: “Regular consumption of chili for 4 weeks increases the resistance of serum lipoproteins to oxidation. Laboratory studies had shown that the resistance of isolated LDL-cholesterol or linoleic acid to oxidation is increased in incubations with chili extracts or capsaicin, the active ingredient of chili.”
Kochujang, a Korean fermented red pepper plus soybean paste, improves glucose homeostasis in 90% pancreatectomized diabetic rats. Kwon DY, Hong SM, Ahn IS, Kim YS, Shin DW, Park S. Nutrition. 2009 Jul-Aug;25(7-8):790-9. Key Finding: Kochujuan, the fermented product of red pepper, and soybeans have been reported to modulate energy and glucose metabolism. “The combination of red pepper and fermented soybeans in kochujang improves glucose homeostasis by reducing insulin resistance.”
Immunosuppressive activity of capsaicinoids: capsiate derived from sweet peppers inhibits NF-kappaB activation and is a potent anti-inflammatory compound in vivo. Sancho R, Lucena C, Macho A, Calzado MA, Blanco-Molina M, Minassi A, Appendino G, Munoz E. Eur J Immunol. 2002 Jun;32(6):1753-63. Key Finding: “These results suggest that capsaicin target specific pathways involved in inflammation, and hold considerable potential for dietary health benefits as well as for pharmaceutical development.”
Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals. Aggarwal BB. Annu Rev Nutr. 2010 Aug 21;30:173-99. Key Finding: “Curcumin-induced alterations reverse insulin resistance, hyperglycemia, hyperlipidemia and other symptoms linked to obesity. Other structurally homologous nutraceuticals, derived from red chili, cinnamon, cloves, black pepper and ginger, also exhibit effects against obesity and insulin resistance.”
Maximum tolerable dose of red pepper decreases fat intake independently of spicy sensation in the mouth. Yoshioka M, Imanaga M, Ueyama H, Yamane M, Kubo Y, Boivin A, St-Amand J, Tanaka H, Kiyonaga A. Br J Nutr. 2004 Jun;91(6):991-5. Key Finding: “The present results indicate that the maximum tolerable dose is necessary to have a suppressive effect of red pepper on fat intake.”
Effects of red pepper on appetite and energy intake. Yoshioka M, St-Pierre S, Drapeau V, Dionne I, Doucet E, Suzuki M, Tremblay A. Br J Nutr. 1999 Aug;82(2):115-23. Key Finding: “These results indicate that the ingestion of red pepper decreases appetite and subsequent protein and fat intakes in Japanese females and energy intake in Caucasian males.”