The Anticancer Role of Capsaicin in Experimentally-induced Lung Carcinogenesis

  • Received : 2015.03.29
  • Accepted : 2015.05.13
  • Published : 2015.06.30


Objectives: Capsaicin (CAP) is the chief pungent principle found in the hot red peppers and the chili peppers that have long been used as spices, food additives and drugs. This study investigated the anticancer potential of CAP through its ability to modify extracellular matrix components and proteases during mice lung carcinogenesis. Methods: Swiss albino mice were treated with benzo(a) pyrene (50 mg/kg body weight dissolved in olive oil) orally twice a week for four successive weeks to induce lung cancer at the end of $14^{th}$ week. CAP was administrated (10 mg/kg body weight dissolved in olive oil) intraperitoneally. Extracellular matrix components were assayed; Masson's trichome staining of lung tissues was performed. Western blot analyses of matrix metalloproteases 2 and 9 were also carried out. Results: In comparison with the control animals, animals in which benzo(a)pyrene had induced lung cancer showed significant increases in extracellular matrix components such as collagen (hydroxy proline), elastin, uronic acid and hexosamine and in glycosaminoglycans such as hyaluronate, chondroitin sulfate, keratan sulfate and dermatan sulfate. The above alterations in extracellular matrix components were effectively counteracted in benzo(a)pyrene along with CAP supplemented animals when compared to benzo(a) pyrene alone supplemented animals. The results of Masson's trichome staining for collagen and of, immunoblotting analyses of matrix metalloproteases 2 and 9 further supported the biochemical findings. Conclusion: The apparent potential of CAP in modulating extracellular matrix components and proteases suggests that CAP plays a chemomodulatory and anti-cancer role working against experimentally induced lung carcinogenesis.


  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30.
  2. Villar V, Kocic J, Santibanez JF. Skip regulates TGF- $\beta$ 1-induced extracellular matrix degrading proteases expression in human PC-3 prostate cancer cells. Prostate Cancer. 2013;2013;1-7.
  3. Premkumar VG, Yuvaraj S, Sathish S, Shanthi P, Sachdanandam P. Anti-angiogenic potential of coenzyme Q10, riboflavin and niacin in breast cancer patients undergoing tamoxifen therapy. Vascul Pharmacol. 2008;48(4-6):191-201.
  4. Lukaszewicz-Zajac M, Mroczko B, Szmitkowski M. Gastric cancer - the role of matrix metalloproteinases in tumor progression. Clin Chim Acta. 2011;412(19-20):1725-30.
  5. Ramakrishnan G, Jagan S, Kamaraj S, Anandakumar P, Devaki T. Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteases-2 and 9 in rat liver carcinogenesis. Invest New Drugs. 2009;27(3):233-40.
  6. Kamaraj S, Anandakumar P, Jagan S, Ramakrishnan G, Devaki T. Modulatory effect of hesperidin on benzo(a) pyrene induced experimental lung carcinogenesis with reference to COX-2, MMP-2 and MMP-9. Eur J Pharmacol. 2009;649(1-3):320-7.
  7. Stellas D, Patsavoudi E. Inhibiting matrix metalloproteinases, an old story with new potentials for cancer treatment. Anticancer Agents Med Chem. 2012;12(7):707-17.
  8. Benetou V, Orfanos P, Lagiou P, Trichopoulos D, Boffetta P, Trichopoulou A. Vegetables and fruits in relation to cancer risk: evidence from the greek EPIC cohort study. Cancer Epidemiol Biomarkers Prev. 2008;17(2):387-92.
  9. Freedman ND, Park Y, Subar AF, Hollenbeck AR, Leitzmann MF, Schatzkin A, et al. Fruit and vegetable intake and head and neck cancer risk in a large United States prospective cohort study. Int J Cancer. 2008;122(10):2330-6.
  10. Cordell GA, Araujo OE. Capsaicin: identification, nomenclature, and pharmacotherapy. Ann Pharmacother. 1993;27(3):330-6.
  11. Chowdhury B, Mukhopadhyay S, Bhattacharayay D, De AK. Capsaicin, a unique anti-oxidant, anti-inflammatory, analgesic compound with antifungal activity against dermatophytes. Med Sci Res. 1996;24(10):669-70.
  12. Lee JG, Yon JM, Lin C, Jung AY, Jung KY, Nam SY. Combined treatment with capsaicin and resveratrol enhances neuroprotection against glutamate-induced toxicity in mouse cerebral cortical neurons. Food Chem Toxicol. 2012;50(11):3877-85.
  13. Miller CH, Zhang Z, Hamilton SM, Teel RW. Effects of capsaicin on liver microsomal metabolism of the tobacco-specific nitrosamine NNK. Cancer Lett. 1993;75(1):45-52.
  14. Kang JY, Alexander B, Math MV, Williamson RC. The effect of chilli and its pungent ingredient capsaicin on gastrointestinal transit in the rat. J Gastroenterol Hepatol. 1993;8(6):513-6.
  15. Pyun BJ, Choi S, Lee YJ, Kim TW, Min JK, Kim YH, et al. Capsiate, a non-pungent capsaicin-like compound, inhibits angiogenesis and vascular permeability via a direct inhibition of Src Kinase Activity. Cancer Res. 2008;68:227-35.
  16. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Devaki T. Capsaicin provokes apoptosis and restricts benzo(a)pyrene induced lung tumorigenesis in Swiss albino mice. Int Immunopharmacol. 2013;17(2):254-9.
  17. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Asokkumar S, Naveenkumar C, et al. Capsaicin inhibits benzo(a)pyrene induced lung carcinogenesis in an in vivo mouse model. Inflamm Res. 2012;61(11):1169-75.
  18. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Naveenkumar C, Asokkumar S, et al. Capsaicin al-leviates the imbalance in xenobiotic metabolizing enzymes and tumor markers during experimental lung tumorigenesis. Mol Cell Biochem. 2009;331(1-2):135-43.
  19. Kato H, Matsumura Y, Maeda H. Isolation and identification of hydroxyproline analogues of bradykinin in human urine. FEBS Lett. 1988;232(1):252-4.
  20. Venturi M, Bonavina L, Annoni F, Colombo L, Butera C, Peracchia A, et al. Biochemical assay of collagen and elastin in the normal and varicose vein wall. J Surg Res. 1996;60(1):245-8.
  21. Elson LA, Morgan WT. A colorimetric method for the determination of glucosamine and chondrosamine. Biochem J. 1933;27(6):1824-8.
  22. Schiller S, Slover GA, Dorfman A. A method for the separation of acid mucopolysaccharides: its application to the isolation of heparin from the skin of rats. J Biol Chem. 1961;236:983-7.
  23. Smith RL, Gilkerson E, Kohatsu N, Merchant T, Schurman DJ. Quantitative microanalysis of synovial fluid and articular cartilage glycosaminoglycans. Anal Biochem. 1980;103(1):191-200.
  24. Breen M, Knepper PA, Weinstein HG, Blacik LJ, Lewandowski DG, Baltrus BM. Microanalysis of glycosaminoglycans. Anal Biochem. 1981;113(2):416-22.
  25. Bosman FT, Stamenkovic I. Functional structure and composition of the extracellular matrix. J Pathol. 2003;200(4):423-8.
  26. Nakoman C, Resmi H, Ay O, Acikel U, Atabey N, Guner G. Effects of basic fibroblast factor (bFGF) on MMP-2, TIMP-2, and type-I collagen levels in human lung carcinoma fibroblasts. Biochimie. 2005;87(3-4):343-51.
  27. Monboisse JC, Borel JP. Oxidative damage to collagen. Exs. 1992;62:323-7.
  28. Torzilli PA, Bourne JW, Cigler T, Vincent CT. A new paradigm for mechano biological mechanisms in tumor metastasis. Semin Cancer Biol. 2012;22(5-6):385-95.
  29. Morita A. Tobacco smoke causes premature skin aging. J Dermatol Sci. 2007;48(3):169-75.
  30. Venkatesan N, Punithavathi D, Chandrakasan G. Biochemical and connective tissue changes in cyclophosphamide-induced lung fibrosis in rats. Biochem Pharmacol. 1998;56(7):895-904.
  31. Nikitovic D, Chatzinikolaou G, Tsiaoussis J, Tsatsakis A, Karamanos NK, Tzanakakis GN. Insights into targeting colon cancer cell fate at the level of proteoglycans/glycosaminoglycans. Curr Med Chem. 2012;19(25):4247-58.
  32. Fujimoto N, Gemba K, Asano M, Fuchimoto Y, Wada S, Ono K, et al. Hyaluronic acid in the pleural fluid of patients with malignant pleural mesothelioma. Respir Investig. 2013;51(2):92-7.
  33. Itano N, Kimata K. [Hyaluronan synthase: a scenario for remodeling the extracellular matrix]. Seikagaku. 1998;70(9):1171-5. Japanese.
  34. Alexander SA, Donoff RB. The glycosaminoglycans of open wounds. J Surg Res. 1980;29(5):422-9.
  35. Gao F, Yang CX, Mo W, Liu YW, He YQ. Hyaluronan oligosaccharides are potential stimulators to angiogenesis via RHAMM mediated signal pathway in wound healing. Clin Invest Med. 2008;31(3):106-16.
  36. Jia XL, Li SY, Dang SS, Cheng YA, Zhang X, Wang WJ, et al. Increased expression of chondroitin sulphate proteoglycans in rat hepatocellular carcinoma tissues. World J Gastroenterol. 2012;18(30):3962-76.
  37. Dinicola S, Pasqualato A, Cucina A, Coluccia P, Ferranti F, Canipari R, et al. Grape seed extract suppresses MDAMB231 breast cancer cell migration and invasion. Eur J Nutr. 2014;53(2):421-31.
  38. Ke P, Wu ZD, Wen HS, Ying MX, Long HC, Qing LG. Current evidence on associations between the MMP-7 (-181A>G) polymorphism and digestive system cancer risk. Asian Pac J Cancer Prev. 2013;14(4):2269-72.
  39. Xu B, Li KP, Shen F, Xiao HQ, Cai WS, Li JL, et al. Ulinastatin reduces cancer recurrence after resection of hepatic metastases from colon cancer by inhibiting MMP-9 activation via the antifibrinolytic pathway. Biomed Res Int. 2013;2013:1-10.
  40. Yen CY, Liang SS, Han LY, Chou HL, Chou CK, Lin SR, et al. Cardiotoxin III inhibits proliferation and migration of oral cancer cells through MAPK and MMP signaling. Scientific World J. 2013;2013:1-5.
  41. Ozden F, Saygin C, Uzunaslan D, Onal B, Durak H, Aki H. Expression of MMP-1, MMP-9 and TIMP-2 in prostate carcinoma and their influence on prognosis and survival. J Cancer Res Clin Oncol. 2013;139(9):1373-82.
  42. Weng Y, Cai M, Zhu J, Geng J, Zhu K, Jin X, et al. Matrix metalloproteinase activity in early-stage lung cancer. Onkologie. 2013;36(5):256-9.

Cited by

  1. Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction vol.8, pp.5, 2016,
  2. An updated review on molecular mechanisms underlying the anticancer effects of capsaicin vol.26, pp.1, 2017,
  3. Food Components in Health Promotion and Disease Prevention 2017,
  4. Punicalagin from pomegranate promotes human papillary thyroid carcinoma BCPAP cell death by triggering ATM-mediated DNA damage response 2017,
  5. Anti-Cancer Effects and Mechanisms of Capsaicin in Chili Peppers vol.06, pp.19, 2015,
  6. Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated Pathways vol.21, pp.10, 2016,
  7. Capsaicin-loaded folic acid-conjugated lipid nanoparticles for enhanced therapeutic efficacy in ovarian cancers vol.91, 2017,
  8. Health-promoting properties of compounds derived from Capsicum sp. A review vol.63, pp.1, 2017,
  9. Applicability of Plant Extracts in Preclinical Studies of Melanoma: A Systematic Review vol.2018, pp.1466-1861, 2018,