Capsaicin and cancer: Guilty as charged or innocent until proven guilty?

References

• Jancsó G, Sántha P. The foundation of sensory pharmacology: Nicholas (Miklós) Jancsó and the Szeged contribution. Temperature. 2015;2: 152–157. DOI:10.1080/23328940.2015.1045683.
   PubMedGoogle Scholar
• Szolcsányi J. Effect of capsaicin on thermoregulation: an update with new aspects. Temperature. 2015;2(2): 277–296. DOI:10.1080/23328940.2015.1048928.
   PubMedGoogle Scholar
• Romanovsky AA. Protecting western red cedar from deer browsing – with a passing reference to TRP channels. Temperature. 2015;2: 142–149. DOI:10.1080/23328940.2015.1047078.
   PubMedGoogle Scholar
• Szallasi A. Some like it hot (even more so in the tropics): a puzzle with no solution. Temperature. 2016;3: 54–55. DOI:10.1080/23328940.2016.1139964.
   PubMedGoogle Scholar
• Derry S, Moore RA. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2012;9: CD010111. DOI:10.1002/14651858.CD010111
   PubMed Web of Science ®Google Scholar
• Derry S, Rice AS, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;1(1):CD007393.
   PubMedGoogle Scholar
• López-Carrillo L, Hernández Avila M, Dubrow R. Chili pepper consumption and gastric cancer in Mexico: a case-control study. Am J Epidemiol. 1994;139: 263–271.
   PubMed Web of Science ®Google Scholar
• Du Y, Lu Y, Zha W, et al. Chili consumption and risk of gastric cancer: a meta-analysis. Nutr Cancer. 2021;73: 45–54.
   PubMed Web of Science ®Google Scholar
• Luo L, Yan J, Wang X, et al. The correlation between chili pepper consumption and gastric cancer risk: a meta-analysis. Asia Pacific J Clin Nutr. 2021;30: 130–139.
   PubMed Web of Science ®Google Scholar
• Zheng J, Zhou Y, Li Y, et al. Spices for prevention and treatment of cancers. Nutrients. 2016;8(8): 495.
   PubMed Web of Science ®Google Scholar
• Chitra S, Viswanathan P, Nalini N, et al. Role of red chili (capsaicin) in the formation of colonic carcinoma. Indian J Pathol Microbiol. 1997;40(1): 21–25.
   PubMedGoogle Scholar
• Ramos Caetano BF, Tablas MB, Goncalves Ignoti M, et al. Capsaicin lacks tumor-promoting effects during colon carcinogenesis in a rat model induced by 1,2-dimethylhydrazine. Environ Sci Pollut Res Int. 2021;28(2): 2457–2467.
   PubMed Web of Science ®Google Scholar
• Bley K, Boorman G, Mohammad B, et al. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol. 2012;40: 847–873.
   PubMed Web of Science ®Google Scholar
• Zhai K, Liskova A, Kubatka P, et al. Calcium entry through TRPV1: a potential target for the regulation of proliferation and apoptosis in cancerous and healthy cells. Int J Mol Sci. 2020;21(11): 4177.
   PubMed Web of Science ®Google Scholar
• Cho SC, Lee H, Choi BY. An updated review on molecular mechanisms underlying the anticancer effects of capsaicin. Food Sci Biotechnol. 2017;26(1): 1–13.
   PubMed Web of Science ®Google Scholar
• de Almeida AS, Barros Bernardes L, Trevisan G. TRP channels in cancer pain. Eur J Pharmacol. 2021;904: 174185.
   PubMed Web of Science ®Google Scholar
• Ellison N, Loprinzi CL, Kugler J, et al. Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients. J Clin Oncol. 1997;15(8): 2974–2980.
   PubMed Web of Science ®Google Scholar
• Surh YJ, Lee SS. Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential. Life Sci. 1995;56: 1845–1855.
   PubMed Web of Science ®Google Scholar
• Vera-Guzmán AM, Aquino-Bolanos EN, Heredia-García E, et al. Flavonoid and capsaicinoid contents and consumption of Mexican chili pepper (capsicum annuum L). Intechopen Chapters. 2016:#54776. DOI:10.5772/68076.
   Google Scholar
• Orellena-Escobedo L, Garcia-Amezquita LE, Olivas GI, et al. Capsaicinoids content and proximate consumption of Mexican chili peppers (capsicum spp.) cultivated in the State of Chihuahua. CyTA. J Food. 2012;11: 179–184.
   Google Scholar
• BfR Opinion No. 053/2011. Too hot isn’t healthy – foods with very high capsaicin concentrations can damage health.
   Google Scholar
• Sampieri CL, Mora M. Gastric cancer research in Mexico: a public health priority. World J Gastroenterol. 2014;20: 4491–4502.
   PubMedGoogle Scholar
• Anand P, Kunnumakkara AB, Sundaram C, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res. 2008;25: 2097–2116.
   PubMed Web of Science ®Google Scholar
• Trujillo Rivera A, Sampieri CL, Romero JM, et al. Risk factors associated with gastric cancer in Mexico: education, breakfast and chili. Rev Esp Enferm Dig. 2018;110: 372–379.
   PubMed Web of Science ®Google Scholar
• Xue GP, Pan XF, Li SG, et al. Association between lifestyle factors and behaviors and risk of gastric cancer, Sichuan Province. Mod Prev Med. 2015;42: 1257–1260.
   Google Scholar
• Mathew A, Gangadharan P, Varghese C, et al. Diet and stomach cancer: a case-control study in South India. Eur J Cancer Prev. 2000;9: 89–97.
   PubMed Web of Science ®Google Scholar
• Munoz N, Plummer M, Visas J, et al. A case-control study of gastric cancer in Venezuela. Int J Cance. 2001;93: 417–423.
   PubMed Web of Science ®Google Scholar
• De Stefani E, Correa P, Boffetta P, et al. Plant foods and risk of gastric cancer: a case-control study in Uruguay. Eur J Cancer Prev. 2001;10: 357–364.
   PubMed Web of Science ®Google Scholar
• Botterweck AA, van Den Brandt PA, Goldbohm RA. A procpective cohort study on vegetable and fruit consumption and stomach cancer risk in the Netherlands. Am J Epidemiol. 1998;148: 842–853.
   PubMed Web of Science ®Google Scholar
• Al G, Vatcheva KP, Pan JJ, et al. Liver and other gastrointestinal cancers are frequent in Mexican Americans. J Racial Eth Health Disparities. 2016;3: 1–10.
   PubMed Web of Science ®Google Scholar
• Sicinschi LA, Lopez-Carillo L, Camargo MC, et al. Gastric cancer risk in a Mexican population: role of Helicobacter pylori CagA positive infection and polymorphism in interleukin 1- and 10 genes. Int J Cancer. 2006;118: 649–657.
   PubMed Web of Science ®Google Scholar
• Lopez-Carillo L, Camargo MC, Schneider BG, et al. Capsaicin consumption, helicobacter pylori CagA status and IL1B 31C>T genotypes: a host and environment interaction in gastric cancer. Food Chem Toxicol. 2012;50: 2118–2122.
   PubMed Web of Science ®Google Scholar
• Chopan M, Littenberg B. The association of hot red chili pepper consumption and mortality: a large population-based cohort study. PloS ONE. 2017;12: e0169876.
   PubMed Web of Science ®Google Scholar
• Lv J, Qi L, Yu C, et al. Consumption of spicy food and total and cause specific mortality: population based cohort study. BMJ. 2015: h3942. DOI:10.1136/bmj.h3942.
   PubMedGoogle Scholar
• Craddock C, Cathcart P, Stebbing J. Chilli – too hot to handle? Lancet Oncol. 2017;18(8): 1005.
   PubMed Web of Science ®Google Scholar
• Agrawal RC, Wiessler M, Hecker E, et al. Tumour-promoting effect of chilli extract in BALB/c mice. Int J Cancer. 1986;38: 689–695.
   PubMed Web of Science ®Google Scholar
• Akagi A, Sano N, Uehara H, et al. Non-carcinogenecity of capsaicinoids in B6C3F1 mice. Food Chem Toxicol. 1998;36: 1065–1071.
   PubMed Web of Science ®Google Scholar
• Toth B, Gannett P. Carcinogenicity of lifelong administration of capsaicin of hot pepper in mice. In Vivo. 1992;6: 59–63.
   PubMedGoogle Scholar
• Ramos Caetano BF, Baptista Tablas M, Goncalves Ignoti M, et al. Capsaicin lacks tumor-promoting effects during colon carcinogenesis in a rat model induced by 1,2-dimethylhydrazine. Environ Sci Pollut Res Int. 2021;28: 2457–2467.
   PubMed Web of Science ®Google Scholar
• Lee SD. Influences of diets and lipotrophic substances upon the various organs and metabolic changes in rabbits on long term feeding with red pepper. 1. Histopathological changes of the liver and spleen. Korean J Int Med. 1963;6: 383–395.
   Google Scholar
• Bitencourt S, Stradiot L, Verhulst S, et al. Inhibitory effect of dietary capsaicin on liver fibrosis in mice. Mol Nutr Food Res. 2015;59: 1107–1116.
   PubMed Web of Science ®Google Scholar
• Hoch-Ligetti G. Production of liver tumours by dietary means: effect of feeding chillies to rats. Acta Unio Int Cancer. 1951;7: 606–611.
   PubMedGoogle Scholar
• Barani A, Nasiri Z, Jarrah N. Natural occurrence of Aflatoxins in commercial pepper in Iran. Food Agricult Immunol. 2016;27: 570–576.
   Web of Science ®Google Scholar
• Sarmiento-Machado LM, Ribeiro Romualdo G, Zapaterini JR, et al. Protective effects of dietary capsaicin on the initiation step of a two-stage hepatocarcinogenesis rat model. Nutr Cancer. 2021;73: 817–828.
   PubMed Web of Science ®Google Scholar
• Xie C, Liu G, Li M, et al. Targeting TRPV1 on cellular plasticity regulated by Ovol 2 and Zeb 1 in hepatocellular carcinoma. Biomed Pharmacother. 2019;118: 109270.
   PubMed Web of Science ®Google Scholar
• El-Kott A, Bin-Meferij MM. Suppressive effects of capsaicin against N-nitrosomethylurea-induced mammary tumorigenesis in rats. Biomed Pharmacother. 2018;98: 673–679.
   PubMed Web of Science ®Google Scholar
• Venier NA, Yamamoto T, Sugar LM, et al. Capsaicin reduced the metastatic burden in the mouse transgenic adenocarcinoma of the prostate model. Prostate. 2015;75: 1300–1311.
   PubMed Web of Science ®Google Scholar
• Jankovic B, Loblaw DA, Nam R. Capsaicin may slow PSA doubling time: case report and literature review. Can Urol Assoc J. 2010;4: E9–E11.
   PubMedGoogle Scholar
• Kallifatidis G, Hoy JJ, Lokeshwar BL. Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer. Semin Cancer Biol. 2016;41: 160–169.
   Web of Science ®Google Scholar
• Djamgoz MBA, Jentzch V. Integrative management of pancreatic cancer (PDAC): emerging complementary agents and modalities. Nutr Cancer. 2021; 1–24. DOI:10.1080/01635581.2021.1934043.59
   Web of Science ®Google Scholar
• Benzel J, Fendrich V. Chemoprevention and treatment of pancreatic cancer: update and review of the literature. Digestion. 2018;97: 275–287.
   PubMed Web of Science ®Google Scholar
• Wang Y, Deng X, Yu C, et al. Synergistic inhibitory effects of capsaicin combined with cisplatin on human osteosarcoma in culture and in xenografts. J Exp Clin Cancer Res. 2018;37(1): 251.
   PubMedGoogle Scholar
• Bort A, Spinola E, Rodriguez-Henche N, et al. Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation. Oncotarget. 2017;8: 84687–87698.
   Google Scholar
• Szolcsányi J. Forty years in capsaicin research for sensory pharmacology and physiology. Neuropeptides. 2004;38: 377–384.
   PubMed Web of Science ®Google Scholar
• Holzer P. Capsaicin: cellular tagets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev. 1991;43: 143–201.
   PubMed Web of Science ®Google Scholar
• Szallasi A, Blumberg PM. Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev. 1999;51: 159–212.
   PubMed Web of Science ®Google Scholar
• Caterina MJ, Schumacher MA, Tominaga A, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389: 816–824.
   PubMed Web of Science ®Google Scholar
• Patapoutian A, Peier AM, Story GM, et al. Thermo TRP channels and beyond: mechanisms of temperature sensing. Nat Rev Neurosci. 2003;4: 529–539.
   PubMed Web of Science ®Google Scholar
• Banerjee S, McCormack S. Capsaicin for acute and chronic non-cancer pain: a review of clinical effectiveness, safety, and cost-effectiveness (Internet). CADTH Rapid Response Reports. 2020. PMID33284564.
   Google Scholar
• Ozawa H, Jung SY, Fraser MO, et al. Intravesical capsaicin therapy: a review. J Spinal Cord Med. 1999;22: 114–118.
   PubMedGoogle Scholar
• Bonezzi C, Costantini A, Cruccu G, et al. Capsaicin 8% dermal patch in clinical practice: an expert opinion. Expert Opin Pharmacother. 2020;21: 1377–2387.
   PubMed Web of Science ®Google Scholar
• Giaccari LG, Aurilio C, Coppolino F, et al. Capsaicin 8% patch and chronic postsurgical neuropathic pain. J Pers Med. 2021;11(10): 960.
   PubMed Web of Science ®Google Scholar
• Campbell JN, Stevens R, Hanson P, et al. Injectable capsaicin for the management of pain due to osteoarthritis. Molecules. 2021;26(4): 778.
   PubMed Web of Science ®Google Scholar
• GlobalData Pharmapoint. Qutenza (neuropathic pain) – forecast and market analysis to 2022. http://marketresearch.com/product/sample-8161593.pdf
   Google Scholar
• Qutenza (capsaicin 8% patch): uses, dosage, side effects. https://www.rxlist.com>qutenza-dug.
   Google Scholar
• Malmberg AB, Mizisin AP, Calcutt NA, et al. Reduced heat sensitivity and epidermal nerve fiber immunostaining following single applications of a high-concentration capsaicin patch. Pain. 2004;111: 360–367.
   PubMed Web of Science ®Google Scholar
• Cruz F, Guimaraes M, Silva C, et al. Suppression of bladder hyperreflexia by intravesical resiniferatoxin. Lancet. 1997;350: 640–641.
   PubMed Web of Science ®Google Scholar
• Foster HE, Lake AMG. Use of vanilloids in urologic disorders. Prog Drug Res. 2014;68: 307–317.
   PubMedGoogle Scholar
• Silva C, Avelino A, Souto-Moura C, et al. A light- and electronmicroscopic histopathological study of human bladder mucosa after intravesical resiniferatoxin application. BJU Int. 2001;88: 355–360.
   PubMed Web of Science ®Google Scholar
• Hergenhahn M, Adolf W, Hecker E. Resiniferatoxin and other esters of novel polyfunctional diterpenes from Euphorbia resinifera and unispina. Tetrahedron Lett. 1975;16: 19–20.
   Google Scholar
• Zur Hausen H, Bornkamm GW, Schmidt R, et al. Tumor initiators and promoters in the induction of the Epstein-Barr virus. Proc Natl Acad Sci USA. 1979;76: 782–785.
   PubMed Web of Science ®Google Scholar
• Szallasi A, Blumberg PM. Neurogenic component of phorbol ester-induced mouse skin inflammation. Cancer Res. 1989;49: 6052–6057.
   PubMed Web of Science ®Google Scholar
• Szallasi A, Blumberg PM. Effect of resiniferatoxin pretreatment on the inflammatory response to phorbol-12-mzristate-13-acetate in mouse strains with different susceptibilities to phorbol ester tumor promotion. Carcinogenesis. 1990;11: 583–587.
   PubMed Web of Science ®Google Scholar
• Park KK, Surh YJ. Effects of capsaicin on chemically induced two-stage mouse skin carcinogenesis. Cancer Lett. 1997;114: 183–185.
   PubMed Web of Science ®Google Scholar
• Han SS, Keum YS, Seo HJ, et al. Capsaicin suppresses phorbol ester-induced activation of NF-kappaB/Rel and AP-1 transcription factors in mouse epidermis. Cancer Lett. 2001;164: 119–126.
   PubMed Web of Science ®Google Scholar
• Park KK, Chun KS, Yook JI, et al. Lack of tumor promoting activity of capsaicin, a principle pungent ingredient in red pepper, in mouse skin carcinogenesis. Anticancer Res. 1998;18: 4201–4205.
   PubMed Web of Science ®Google Scholar
• Chanda S, Erexson G, Frost D, et al. 26-week dermal oncogenicity study evaluating pure trans-capsaicin in Tg.AC hemizygous mice (FBV/N). Int J Toxicol. 2007;26: 123–133.
   PubMed Web of Science ®Google Scholar
• Liu Z, Zhu P, Tao Y, et al. Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice. Food Chem Toxicol. 2015;81: 1–8.
   PubMed Web of Science ®Google Scholar
• Hwang MK, Bode AM, Byun S, et al. Cocarcinogenic effect of capsaicin involves activation of EGFR signalling but not TRPV1. Cancer Res. 2010;70: 6859–6869.
   PubMed Web of Science ®Google Scholar
• Braga Ferreira LG, Faria JV, Dos Santos JPS, et al. Capsaicin: TRPV1-independent mechanisms and novel therapeutic possibilities. Eur J Pharmacol. 2020;887: 173356.
   PubMed Web of Science ®Google Scholar
• Torrecillas A, Schneider M, Fernandez-Martinez AM, et al. Capsaicin fluidifies the membrane and localizes itself near the lipid-water interphase. ACS Chem Neurosci. 2015;6: 1741–1750.
   PubMed Web of Science ®Google Scholar
• Williams SR, Clark RF, Dunford JV. Contact dermatitis associated with capsaicin: hunan hand syndrome. Ann Emerg Med. 1995;25: 713–715.
   PubMed Web of Science ®Google Scholar
• Szallasi A, Cortright DN, Bloom CA, et al. The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept. Nat Rev Drug Discov. 2007;6: 357–372.
   PubMed Web of Science ®Google Scholar
• Brederson JD, Kym PR, Szallasi A. Targeting TRP channels for pain relief. Eur J Pharmacol. 2013;716: 61–76.
   PubMed Web of Science ®Google Scholar
• Park M, Naidoo A, Burns A, et al. Do TRPV1 antagonists increase the risk for skin tumourigenesis? A collaborative in vitro and in vivo assessment. Cell Biol Toxicol. 2018;34: 143–162.
   PubMed Web of Science ®Google Scholar
• Choi JK, Cho W, Lee JH, et al. A TRPV1 antagonist, PAC-14028, does not increase the risk of tumorigenesis in chemically induced mouse skin carcinogenesis. Regul Toxicol Pharmacol. 2020;112: 104613.
   PubMed Web of Science ®Google Scholar
• Li S, Bode AM, Zhu F, et al. TRPV1-antagonist AMG9810 promotes mouse skin tumorigenesis through EGFR/Akt signaling. Carcinogenesis. 2011;32: 779–785.
   PubMed Web of Science ®Google Scholar
• Park YR, Chun JN, So I, et al. Data-driven analysis of TRP channels in cancer: linking variation in gene expression to clinical significance. Cancer Genom Proteom. 2016;13: 83–90.
   PubMed Web of Science ®Google Scholar
• Lu M, Chen C, Lan Y, et al. Capsaicin – the major bioactive ingredient of chili peppers: bio-efficacy and delivery systems. Food Function. 2020;11: 2848–2860.
   PubMed Web of Science ®Google Scholar
• Jia G, Cang S, Ma P, et al. Capsaicin: a „hot” KDM1A/LSD1 inhibitor from peppers. Bioorg Chem. 2020;103: 104161.
   PubMed Web of Science ®Google Scholar
• Szallasi A, Blumberg PM. Specific binding of resiniferatoxin, an ultrapotent capsaicin analog, by dorsal root ganglion membranes. Brain Res. 1990;524: 106–111.
   PubMed Web of Science ®Google Scholar
• Chiang C, Zhang M, Wang D, et al. Therapeutic potential of targeting MKK3-p38 axis with capsaicin for nasopharyngeal carcinoma. Theranostics. 2020;10: 7906–7920.
   PubMed Web of Science ®Google Scholar
• Wu D, Jia H, Zhang Z, et al. Capsaicin suppresses breast cancer cell viability by regulating the CDK8/PI3K/Akt/Wnt/β-catenin pathway. Mol Med Rep. 2020;22: 4868–4876.
   PubMed Web of Science ®Google Scholar
• Zhu M, Yu X, Zheng Z, et al. Capsaicin suppressed activity of prostate cancer stem cells by inhibition of Wnt/β-catenin pathway. Phytother Res. 2020;34: 817–824.
   PubMed Web of Science ®Google Scholar
• Sterle I, Zupančič D, Romih R. Correlation between urothelial differentiation and sensory proteins P2X3, P2X5, TRPV1, and TRPV4 in normal urothelium and papillary carcinoma of human bladder. Biomed Res Int. 2014;2014: 805236.
   PubMed Web of Science ®Google Scholar
• Weber LV, Al-Refae K, Wölk G, et al. Expression and functionality of TRPV1 in breast cancer. Breast Cancer (Dove Med Press). 2016;8: 243–252.
   PubMed Web of Science ®Google Scholar
• Contassot E, Tenan M, Schnüriger V, et al. Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1. Gynecol Oncol. 2004;93: 182–188.
   PubMed Web of Science ®Google Scholar
• Dömötör A, Peidl Z, Vincze A, et al. Immunohistochemical distribution of vanilloid receptor, calcitonin gene-related peptide and substance P in gastrointestinal mucosa of patients with different gastrointestinal disorders. Inflammopharmacol. 2005;13: 161–177.
   PubMedGoogle Scholar
• Wu YY, Liu XY, Zhuo DX, et al. Decreased expression of TRPV1 in renal cell carcinoma: association with tumor Fuhrman grades and histopathological subtypes. Cancer Maneg Res. 2018;10: 1647–1655.
   Google Scholar
• Miao X, Liu G, Xu X, et al. High expression of vanilloid receptor-1 is associated with better prognosis of patients with hepatocellular carcinoma. Cancer Genet Cytogenet. 2008;186: 25–32.
   PubMedGoogle Scholar
• Czifra G, Varga A, Nyeste K, et al. Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma. J Cancer Res Clin Oncol. 2009;135: 507–514.
   PubMed Web of Science ®Google Scholar
• Xu S, Zhang L, Cheng X, et al. Capsaicin inhibits the metastasis of human papillary thyroid carcinoma BCPAP cells through the modulation of the TRPV1 channel. Food Funct. 2018;9(1): 344–354.
   PubMed Web of Science ®Google Scholar
• Fonseca BM, Correia-de-silva G, Teixeira NA. Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors and apoptosis. J Physiol Biochem. 2018;74: 261–272.
   PubMed Web of Science ®Google Scholar
• Hayes AG, Oxford A, Reynolds M, et al. The effects of a series of capsaicin analogues on nociception and body temperature in the rat. Life Sci. 1984;34: 1241–1248.
   PubMed Web of Science ®Google Scholar
• Giles TD, Sander GE. Comparative cardiovascular responses to intravenous capsaicin, phenyldiguanide, veratrum alkaloids and enkephalins in the conscious dog. J Auton Pharmacol. 1986;6: 1–7.
   PubMedGoogle Scholar
• Pórszász J, György L, Pórszász-Gibiszer K. Cardiovascular and respiratory effects of capsaicin. Acta Physiol Hung. 1955;8: 61–76.
   PubMedGoogle Scholar
• Kiss F, Pohóczky K, Szallasi A, et al. Transient Receptor Potential (TRP) channels in head-and-neck squamous cell carcinomas: diagnostic, prognostic and therapeutic potential. Int J Mol Sci. 2020;21(17): 6374.
   PubMed Web of Science ®Google Scholar
• Scheff NN, Saloman JL. Neuroimmunology of cancer and associated symptomology. Immunol Cell Biol. 2021;99(9): 949–961.
   PubMed Web of Science ®Google Scholar
• Cortese N, Rigamonti A, Mantovani A, et al. The neuro-immune axis in cancer: relevance of the peripheral nervous system to the disease. Immunol Lett. 2020;227: 60–65.
   PubMed Web of Science ®Google Scholar
• Shurin MR, Shurin GV, Zlotnikov SB, et al. The neuroimmune axis in the tumor microenvironment. J Immunol. 2020;204: 280–285.
   PubMed Web of Science ®Google Scholar
• Szallasi A, Cortright DN. The role of the vanilloid and related receptors in nociceptor function and neuroimmune regulation. NeuroImmune Biol. 2009;8: 101–117.
   Google Scholar
• Bujak JK, Kosmala D, Szopa IM, et al. Inflammation, cancer, and immunity – implication of the TRPV1 channel. Front Oncol. 2019;9. https://www.frontiersin.org/articles/10.3389/fonc.2019.01087/full
   PubMed Web of Science ®Google Scholar
• Ebrahimi S, Javid H, Alaei A, et al. New insights into the role of the substanceP/neurokinin-1 receptor system in breast cancer progression and its crosstalk with microRNAs. Clin Genet. 2020;98: 322–330.
   PubMed Web of Science ®Google Scholar
• Yoneda T, Hiasa M, Okui T, et al. Sensory nerves: a driver of the vicious cycle in bone metastasis? J Bone Oncol. 2021;30: 100387.
   PubMed Web of Science ®Google Scholar
• Erin N. Role of sensory neurons, neuroimmune pathways, and transient receptor potential vanilloid-1 (TRPV1) channels in a murine model of breast cancer metastasis. Cancer Immunol Immunother. 2020;69: 307–314.
   PubMed Web of Science ®Google Scholar
• Austin M, Elliott L, Nicolaou N, et al. Breast cancer induced aberrant growth and collateral sensory axonal branching. Oncotarget. 2017;8: 76606–76621.
   PubMedGoogle Scholar
• Erin N, Boyer PJ, Bonneau RH, et al. Capsaicin-mediated denervation of sensory neurons promotes mammary tumor metastasis to lung and heart. Anticancer Res. 2004;24: 1003–1009.
   PubMed Web of Science ®Google Scholar
• Bencze N, Schvarc C, Kriszta G, et al. Desensitization of capsaicin-sensitive afferents accelerates early tumor growth via increased vascular leakage in a murine model of triple negative breast cancer. Front Oncol. 2021;11. DOI:10.3389/fonc.2021.685297.
   PubMed Web of Science ®Google Scholar
• Rodriguez E, Pei G, Kim ST, et al. Substance P antagonism as a novel therapeutic option to enhance efficacy of cisplatin in triple negative breast cancer and protect PC12 cells against cisplatin-induced oxidative stress and apoptosis. Cancers (Basel). 2021;13(15): 3871.
   PubMed Web of Science ®Google Scholar
• de Brito Bello RS, Naliwaiko K, Vicentini MS, et al. Nutrition and cancer: capsaicin treatment reduces tumor growth, tumor cell proliferation ex vivo and partially reverses cancer cahexia in Walker 256 tumor-bearing rats. Nutr Cancer. 2019;71: 111–117.
   PubMed Web of Science ®Google Scholar
• Saloman JL, Albers KM, Li D, et al. Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer. Proc Natl Acad Sci USA. 2016;113: 3078–3083.
   PubMed Web of Science ®Google Scholar
• Ye Y, Bae SS, Viet CT, et al. IB4+ and TRPV1+ sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma. Behav Brain Funct. 2014;10: 5.
   PubMed Web of Science ®Google Scholar
• Ständer S, Moormann C, Schumacher M, et al. Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures. Exp Dermatol. 2004;13: 129–139.
   PubMed Web of Science ®Google Scholar
• Golech SA, McCarron RM, Chen Y, et al. Human brain endothelium: co-expression and function of vanilloid and endocannabinoid receptors. Brain Res Mol Brain Res. 2004;132: 87–92.
   PubMedGoogle Scholar
• Omari SA, Adams MJ, Geraghty DP. TRPV1 channels in immune cells and hematological malignancies. Adv Pharmacol. 2017;79: 173–198.
   PubMedGoogle Scholar
• Fischer MJ, Ciotu CI, Szallasi A. The mysteries of capsaicin-sensitive afferents. Front Physiol. 2020;11: 554195.
   PubMed Web of Science ®Google Scholar
• Caterina MJ, Leffler A, Malmberg A, et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000;288: 306–313.
   PubMed Web of Science ®Google Scholar
• Davis JB, Gray J, Gunthorpe MJ, et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature. 2000;405: 183–187.
   PubMed Web of Science ®Google Scholar
• Huang R, Wang F, Yang Y, et al. Recurrent activations of transient receptor potential vanilloid-1 and 4 promote cellular proliferation and migration in esophageal squamous cell carcinoma cells. FEBS Open Biol. 2019;9: 206–225.
   PubMed Web of Science ®Google Scholar
• Marincsák R, Tóth BI, Czifra G, et al. Increased expression of TRPV1 in squamous cell carcinoma of the human tongue. Oral Dis. 2009;15: 328–335.
   PubMed Web of Science ®Google Scholar
• Sakakibara A, Sakakibara S, Kusumoto J, et al. Upregulated expression of Transient Receptor Potential cation channel subfamily V receptors in mucosae of patients with oral squamous cell carcinoma and patients with history of alcohol consumption and smoking. PloS ONE. 2017;12: e0169732.
   PubMed Web of Science ®Google Scholar
• Castillo K, Diaz-Franulic I, Canan J, et al. Thermally activated TRP channels: molecular sensors for temperature detection. Phys Biol. 2018;15(2): 021001.
   PubMed Web of Science ®Google Scholar
• Krenács T, Meggyesházi N, Forika G, et al. Modulated electro hyperthermia-induced tumor damage mechanisms revealed in cancer models. Int J Mol Sci. 2020;21(17): 6270.
   PubMed Web of Science ®Google Scholar
• Yang Y, Guo W, Ma J, et al. Downregulated TRPV1 expression contributes to melanoma growth via the calcineurin-ATF3-p53 pathway. J Invest Dermatol. 2018;138: 2205–2215.
   PubMed Web of Science ®Google Scholar
• Ackermann K, Wallner S, Brochhausen C, et al. Expression profiles of ASIC1/2 and TRPV1/4 in common skin tumors. Int J Mol Sci. 2021;22(11): 6024.
   PubMed Web of Science ®Google Scholar
• Gao N, Yang F, Chen S, et al. The role of TRPV1 ion channels in the suppression of gastric cancer development. J Exp Clin Cancer Res. 2020;39(1): 206.
   PubMed Web of Science ®Google Scholar
• Lozano C, Cordova C, Marchant I, et al. Intracellular aggregated TRPV1 is associated with lower survival in breast cancer patients. Breast Cancer (Dove Med Press). 2018;10: 161–168.
   PubMed Web of Science ®Google Scholar
• Hot peppers may be the spice of long life and healthy heart.https://www.medpagetoday.com/primarycare/dietnutrition/83929
   Google Scholar
• Ugly dangers of eating spicy foods, according to science.htts://www.eatthis.com/news-ugly-dangers-spicy-foods
   Google Scholar