In contrast, another study showed grossly visible gastric bleeding and mucosal microbleeding after consumption of red and black pepper (31). 8600 Rockville Pike Pure capsaicin, a hydrophobic, colorless, odorless, and crystalline-to-waxy solid at room temperature, measures 16,000,000 SHU. At the same time, one should note that hot pepper consumption is not equivalent to the use of pure capsaicin. Overall, animal studies suggest no apparent relationship between mode of administration (i.e., i.p., oral, or topical application) and susceptibility to cancer development. Capsaicin induced a further induction of TPA-increased COX-2 expression in EGFR/WT cells, but not in EGFR/KO cells. Although it is widely consumed throughout the world, capsaicin has a long and convoluted history of controversy, showing two faces, about whether its consumption or topical application is entirely safe. In contrast to the results of cellular and animal studies, several epidemiologic studies seem to indicate that consumption of hot peppers, which contain various levels of capsaicin, might be associated with an increased risk of cancer, and especially gallbladder (23) or gastric cancer (24). Despite these limitations, the studies are cited continually in the literature as support for a cancer-promoting or causative effect of capsaicin. Capsaicin potently suppresses the growth of human prostate carcinoma cells in vitro and in vivo. Capsaicin inhibits human prostate cancer cells growing in mice in vivo. Füchtbauer S, Mousavi S, Bereswill S, Heimesaat MM. However, even in this arena, evidence for the effectiveness or safety of capsaicin use in pain relief is controversial. However, capsaicin has also been reported to be mutagenic and to induce an increase in the cell viability and proliferation of the androgen-responsive prostate cancer LNCaP cells corresponding with increased androgen receptor expression . Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide; Fig. In a review of double-blind placebo-controlled trials pooled for analysis of neuropathic conditions or musculoskeletal conditions, topically applied capsaicin exhibited moderate-to-poor efficacy (46). In contrast, mice fed up to a 0.25% capsaicinoid mixture (64% capsaicin and 32.6% dihydrocapsaicin) in the diet for 79 weeks showed no evidence of carcinogenicity (17). A major, but predictable, conclusion was that capsaicin is a skin irritant even at low concentrations. Notably, local administration of capsaicin resulted in adverse events or even in an increase of pain above tolerable levels in about one third of patients suffering from musculocutaneous or neuropathic pain (46). For example, red chili powder was found to be a risk factor for cancer of the oral cavity, pharynx, esophagus, and larynx in India (25). Although widely consumed, capsaicin has a long and convoluted history of debate about whether its consumption or topical use is entirely safe. A condition known as “Hunan hand,” which is a form of contact dermatitis, has been noted in workers handling peppers (39). Transgenic and knockout mouse models are very powerful but also have substantial limitations. Degeneration of epidermal nerve fibers has been suggested to contribute to the analgesic effect credited to capsaicin (35). The American Institute for Cancer Research noted in its February 2007 newsletter that capsaicin has shown some promise in the fight against cancer. Diet or menu for fighting cancer. We have found that chronic, long-term topical application of capsaicin increased skin carcinogenesis in mice treated with a tumor promoter. Treats Psoriasis. Capsaicin down-regulated the expression of not only prostate … These results might imply that caution should be exercised when using capsaicin-containing topical applications in the presence of a tumor promoter, such as, for example, sunlight. Bell peppers rank lowest at 0 SHU, jalapeños score 3,000 to 6,000 SHU, and habaneros generate 300,000 SHU. Cell Biochem Biophys. Another study conducted by the UCLA School of Medicine that the substance can hamper the growth of prostate cells. Capsaicin is unique among naturally occurring irritant compounds because the initial neuronal excitation evoked is followed by a long-lasting refractory period, during which the previously excited neurons are no longer responsive to a broad range of stimuli. This discrepancy might be due, at least partially, to the inherent difficulty, such as frequent need to renew primary cultures because of dedifferentiation, in studying the effects of capsaicin in relevant “normal cell” control groups for comparison with cancer cells, which are pathologic. However, capsaicin has also been reported to be mutagenic (9) and to induce an increase in the cell viability and proliferation of the androgen-responsive prostate cancer LNCaP cells corresponding with increased androgen receptor expression (10). Repeated topical applications of capsaicin alone failed to promote 7,12dimethylbenz(a)anthracene (DMBA)–initiated mouse skin tumorigenesis but moderately inhibited the papilloma formation when given prior to each topical dose of phorbol ester (21). Journal of Cancer Research ISSN: 0099-7013 The continuing controversy surrounding consumption or topical application of capsaicin clearly suggests that more well-controlled epidemiologic studies are needed to evaluate the safety and efficacy of capsaicin use. In recent years, natural products have emerged as modulators of many cellular responses, with potential applications as therapeutic drugs in many disorders. Accessibility Dermal application of capsaicin did not result in an increased incidence of preneoplastic or neoplastic skin lesions in male or female Tg.AC mice (20). Investigators evaluated the compound capsaicin, which is responsible for the heat from chili peppers, and is commonly used in pain relieving creams. Cancer Research Print ISSN: 0008-5472 Capsaicin is the principal pungent component in hot peppers. It can kill prostate cancer cells, bone cancer cells and pancreatic cancer cells, just to name a few. Skin irritation and other tumor-promoting effects of capsaicin seem to be mediated mainly through interaction with the TRPV1, and the authors suggested that a potent tumor promoter might also be a moderate-to-severe skin irritant. For example, most cancer studies rely heavily on transformed cell lines or mouse models. Wang HM, Chuang SM, Su YC, Li YH, Chueh PJ. The TRPV1 is the first membrane receptor shown to have a tumor-suppressing effect associated with the downregulation of another membrane receptor. Bethesda, MD 20894, Copyright However, the data also suggest that total blockade of the TRPV1 for pain relief or chronic, long-term topical application of capsaicin might increase the risk of skin cancer, especially in the presence of a tumor promoter, such as, for example, sunlight. Capsaicin also induces ceramide accumulation and endoplasmic reticulum stress in androgen-resistant prostate cells. Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells. Piperine research show promising results on prostate cancer. 2019 Jan 15;2019:7462513. doi: 10.1155/2019/7462513. to adult male mice over an 8-week period, had no mutagenic effects (19). Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. Spicy food and the stomach. Capsaicin is the key ingredient in the experimental drug Adlea (ALRGX-4975; Anesiva, Inc.), which is in phase III trials as a long-acting analgesic to treat postsurgical and osteoarthritis pain for weeks to months after a single injection to the site of pain (34). In 2006, a study found that capsaicin can cause prostate cancer cells in mice to die while leaving healthy cells alone. Although unheard of in Africa and Asia until its introduction by Europeans, the chili pepper has since become an essential ingredient of numerous other cuisines, including those of Ethiopia, India, Indonesia, Korea, Laos, Malaysia, Pakistan, Southwest China, Sri Lanka, Thailand, and others. It required, however, giving the … Conflicting epidemiologic data and basic research study results suggest that capsaicin can act as a carcinogen or as a cancer preventive agent. Capsaicin: From Plants to a Cancer-Suppressing Agent. Capsaicin has the ability to unmask cancerous tumors. Most are descriptive, correlative studies and draw speculative conclusions. Most patients preferred the capsaicin treatment over the placebo in spite of some toxic side effects that included coughing and burning and redness of the skin (43). For PCa, animal studies demonstrated that less aggressive tumors developed in animals treated with capsaicin, which also seemed to lead to less tumor growth and spread. Selected Office Based Anticancer Treatment Strategies. eCollection 2019. Capsaicin, the compound responsible for chilis' heat, is used in creams sold to relieve pain, and recent research shows that in high doses, it kills prostate cancer cells. /EXPL THER/ Capsaicin, the active compound in chili peppers, has demonstrated anti-carcinogenic properties in vitro in a number of malignancies, including the prostate. Capsaicin has shown several antitumor properties in lung and breast cancers, and is being studied with other types of cancer. Even cell lines derived from the same tissue source can yield contradictory information, which makes the extrapolation of data from cell lines to the human patient meaningless. Evaluation by videoendoscopy, Effect of red pepper and black pepper on the stomach, The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept, Review of the effectiveness of capsaicin for painful cutaneous disorders and neural dysfunction, Adlea (ALGRX-4975), an injectable capsaicin (TRPV1 receptor agonist) formulation for longlasting pain relief, Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation, Pharmacokinetic analysis of capsaicin after topical administration of a high-concentration capsaicin patch to patients with peripheral neuropathic pain, Topical capsaicin for chronic neuropathic pain in adults, Topical antacid therapy for capsaicin-induced dermal pain: a poison center telephone-directed study, Contact dermatitis associated with capsaicin: Hunan hand syndrome, Vascular and psychophysical effects of topical capsaicin application to orofacial tissues, Topical capsaicin therapy for uremic pruritus in patients on hemodialysis, Lack of efficacy of topical capsaicin in serotonin-induced itch, Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients, Oral capsaicin provides temporary relief for oral mucositis pain secondary to chemotherapy/radiation therapy, Topical capsaicin in the management of HIV-associated peripheral neuropathy, Systematic review of topical capsaicin for the treatment of chronic pain, Coronary vasospasm and acute myocardial infarction induced by a topical capsaicin patch, Transient receptor potential type vanilloid 1 suppresses skin carcinogenesis, Cocarcinogenic effect of capsaicin involves activation of EGFR signaling but not TRPV1, Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin, Macrophage-Based Approaches for Cancer Immunotherapy, Ephs in the Immune Tumor Microenvironment, Cancer Epidemiology, Biomarkers & Prevention, The Conflicting Role of Capsaicin Derived from Cell and Animal Studies, The Controversial Role of Capsaicin Obtained from Human Studies, The Paradox of Topical Application of Capsaicin, Disclosure of Potential Conflicts of Interest. Consumed worldwide, capsaicin has a long and convoluted history of controversy about whether its consumption or topical application is entirely safe. Swiss albino mice fed capsaicin (0.03%) in a semisynthetic diet over their lifetime developed benign polypoid adenomas of the cecum (12). For example, approximately 60% of rats fed a semisynthetic diet, containing 10% chilies, developed neoplastic changes in the liver (11). Here, we report that it has a profound antiproliferative effect on prostate cancer cells, inducing the apoptosis of both androgen receptor (AR)-positive (LNCaP) and -negative (PC-3, DU-145) prostate cancer cell lines associated with an increase of p53, p21, and Bax. The data suggest that, although a great deal of interest has focused on TRPV1 as a target for pain relief, the chronic blockade of this pain receptor might increase the risk for skin cancer development (48).