Capsaicin: From plants to a cancer-suppressing agent

Molecules

Volumn 21, Issue 8, 2016, Pages

  Chapa Oliver, Angela M ^a   Mejía Teniente, Laura ^b  

^a UNIVERSIDAD DE CELAYA   (Mexico)

^b UNIVERSITY OF GUANAJUATO   (Mexico)

Author keywords

Apoptosis; Cancer; Capsaicin; Cell death; Elicitors; Stress

Indexed keywords

ANTINEOPLASTIC AGENT; CAPSAICIN; FOOD ADDITIVE;

BIOSYNTHESIS; CHEMICAL STRUCTURE; CHEMISTRY; HUMAN; METABOLISM; PEPPER; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS, PHYTOGENIC; BIOSYNTHETIC PATHWAYS; CAPSAICIN; CAPSICUM; CELL LINE, TUMOR; FOOD ADDITIVES; HUMANS; MOLECULAR STRUCTURE;

EID: 84982728590     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules21080931     Document Type: Review

References (92)

1. Kim, S.; Park, M.; Yeon, S. I.; Kim, Y. M.; Lee, J. M.; Seo, E.; Choi, J.; Cheong, K.; Kim, K.-T.; Jung, K.; et al. Genome sequence of the hot pepper provides insights into the evolution of pungency in Capsicum species. Nat Genet. 2014, 46, 270-279.
2. Aguilar-Meléndez, A.; Morrell, P. L.; Roose, M. L.; Kim, S. C. Genetic diversity and structure in semiwild and domesticated chiles (Capsicum annuum; Solanaceae) from Mexico. Am. J. Bot. 2009, 96, 1190-1202.
3. Materska, M.; Perucka, I. Antioxidant Activity of the Main Phenolic Compounds Isolated from Hot Pepper Fruit (Capsicum annuum L.). J. Agric. Food Chem. 2005, 53, 1750-1756.
4. Kehie, M.; Kumaria, S.; Tandon, P. Manipulation of culture strategies to enhance capsaicin biosynthesis in suspension and immobilized cell cultures of Capsicum chinense Jacq. cv. Naga King Chili. Bioprocess Biosyst. Eng. 2014, 37, 1055-1063.
5. Govindarajan, V. S.; Sathyanarayana, M. N. Capsicum-production, technology, chemistry, and quality. Part V. Impact on Physiology, Pharmacology, Nutrition, and Metabolism; Structure, Pungency, Pain, and Desensitization Sequences. Crit. Rev. Food Sci. Nutr. 1991, 29, 435-473.
6. Prasad, N. B. C.; Shrivastava, R.; Ravishankar, G. A. Capsaicin as multifaceted drug from Capsicum spp. Evid. Based Int. Med. 2005, 2, 147-166.
7. Curry, J.; Aluru, M.; Mendoza, M.; Nevarez, J.; Melendrez, M.; O'Connell, M. A. Transcripts for posssible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent Capsicum. Plant Sci. 1999, 148, 47-57.
8. European Commission Health & Consumer Protection Directorate-General. Opinion of the Scientific Committee on Food on Capsaicin; European Commission Health & Consumer Protection Directorate-General: Brussel, Belgium, 2002; pp. 1-12.
9. Al-Snafi, A. E. The pharmacological importance of capsicum species (Capsicum annuum and Capsicum frutescens) grown in Iraq. J. Pharm. Biol. 2015, 5, 124-142.
10. 2+ channels. Biochem. Biophys. Res. Comm. 2007, 356, 424-430.
11. Arora, R.; Gill, N. S.; Chauhan, G.; Rana, A. C. An Overview about Versatile Molecule Capsaicin. Int. J. Pharm. Sci. Drug Res. 2011, 3, 280-286.
12. Simone, D. A.; Baumann, T. K.; LaMotte, R. H. Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin. Pain 1989, 38, 99-107.
13. Brederson, J. D.; Kym, P. R.; Szallasi, A. Targeting TRP channels for pain relief. Eur. J. Pharmacol. 2013, 716, 61-76.
14. Galano, A.; Martinez, A. Capsaicin, a tasty free radical scavenger: Mechanism of action and kinetics. J. Phys. Chem. 2012, 116, 1200-1208.
15. Kim, C. S.; Kawada, T.; Kim, B. S.; Han, I. S.; Choe, S. Y. Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peritoneal macrophages. Cell Signal. 2003, 15, 299-306.
16. Kang, J. H.; Kim, C. S.; Han, I. S.; Kawada, T.; Yu, R. Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages. FEBS Lett. 2007, 581, 4389-4396.
17. Bley, K. B.; Boorman, G.; Mohammad, B.; McKenzie, D.; Babbar, S. A Comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol. Pathol. 2012, 40, 847-873.
18. Clark, R.; Lee, S. Anticancer Properties of Capsaicin against Human Cancer. Anticancer Res. 2016, 36, 837-844.
19. Canto-Flick, A.; Balam-Uc, E.; Bello-Bello, J. J.; Lecona-Guzmán, C.; Solís-Marroquín, D.; Avilés-Viñas, S.; Gómez-Uc, E.; López-Puc, G.; Santana-Buzzy, N. Capsaicinoids Content in Habanero Pepper (Capsicum chinense Jacq.): Hottest Known Cultivars. Hortscience 2008, 43, 1344-1349.
20. Bosland, P. W.; Baral, J. B. BhutJolokia the world's hottest known chile pepper is a putative naturally occurring interspecific hybrid. HortScience 2007, 42, 222-224.
21. Iwai, K.; Suzuki, T.; Fujiwake, H. Formation and accumulation of pungent principle of hot pepper fruits, capsaicin and its analogues in Capsicum annuum var. annuum cv. Karayatsubusa at different growth stages after flowering. Agric. Biol. Chem. 1979, 43, 2493-2498.
22. Leete, E.; Louden, M. C. L. Biosynthesis of capsaicin and dihydrocapsaicin in Capsicum frutescens. J. Am. Chem. Soc. 1968, 90, 6837-6841.
23. Ogawa, K.; Murota, K.; Shimura, H.; Furuya, M.; Togawa, Y.; Matsumura, T.; Masuta, C. Evidence of capsaicin synthase activity of the Pun1-encoded protein and its role as a determinantof capsaicinoid accumulation in pepper. BMC Plant Biol. 2015, 15, 1-10.
24. Abraham-Juárez, M. A.; Rocha-Granados, M. C.; López, M. G.; Rivera-Bustamante, R. F.; Ochoa-Alejo, N. Virus-induced silencing of Comt, pAmt and Kas genes resultsin a reduction of capsaicinoid accumulation in chili pepper fruits. Planta 2008, 227, 681-695.
25. Tanaka, Y.; Hosokawa, M.; Miwa, T.; Watanabe, T.; Yazawa, S. Newly mutated putative-aminotransferase in nonpungent pepper (Capsicum annuum) results in biosynthesis of capsinoids, capsaicinoid analogues. J. Agric. Food Chem. 2010, 58, 1761-1767.
26. Qin, C.; Yu, C.; Shen, Y.; Fang, X.; Chen, L.; Min, J.; Cheng, J.; Zhao, S.; Xu, M.; Luo, Y.; et al. Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization. Proc. Natl. Acad. Sci. USA 2014, 111, 5135-5140.
27. Stewart, C.; Mazourek, M.; Stellari, G. M.; O'Connell, M.; Jahn, M. Genetic control ofpungency in C. Chinense via the Pun1 locus. J. Exp. Bot. 2007, 58, 979-991.
28. Topuz, A.; Ozdemir, F. Assessment of carotenoids, capsaicinoids and ascorbic acid composition of some selected pepper cultivars (Capsicum annuum L.) grown in Turkey. J. Food Compos. Anal. 2007, 20, 596-602.
29. Mejía-Teniente, L.; Torres-Pacheco, I.; González-Chavira, M. M.; Ocampo-Velazquez, R. V.; Herrera-Ruiz, G.; Chapa-Oliver, A. M.; Guevara-González, R. G. Use of elicitors as an approach forsustainable agriculture. Afr. J. Biotechnol. 2010, 9, 9155-9162.
30. Mejía-Teniente, L.; Durán-Flores, F. D.; Chapa-Oliver, A. M.; Torres-Pacheco, I.; Cruz-Hernández, A.; González-Chavira, M. M.; Ocampo-Velázquez, R. V.; Guevara-González, R. G. Oxidative and Molecular Responses in Capsicum annuum L. after Hydrogen Peroxide, Salicylic Acid and Chitosan Foliar Applications. Int. J. Mol. Sci. 2013, 14, 10178-10196.
31. Vargas-Hernández, M.; Torres-Pacheco, I.; Gautier, F.; Álvarez-Mayorga, B.; Cruz-Hernández, A.; García-Mier, L.; Jiménez-García, S. N.; Ocampo-Velázquez, R. V.; Feregrino-Perez, A. A.; Guevara-González, R. G. Influence of hydrogen peroxide foliar applications on in vitro antimicrobial activity in Capsicum chinense Jacq. Plant Biosyst. Int. J. Deal. Asp. Plant Biol. 2016.
32. García-Mier, L.; Guevara-González, R. G.; Mondragón-Olguín, V. M.; del Verduzco-Cuellar, B. R.; Torres-Pacheco, I. Agriculture and bioactives: Achieving both crop yield and phytochemicals. Int. J. Mol. Sci. 2013, 14, 4203-4222.
33. Gururaj, H. B.; Giridhar, P.; Ravishankar, G. A. Laminarin as a potential non-conventional elicitor for enhancement ofcapsaicinoid metabolites. Asian J. Plant Sci. Res. 2012, 2, 490-495.
34. Suresh, B.; Ravishankar, G. A. Methyl jasmonate modulated biotransformation of phenylpropanoidsto vanillin related metabolites using Capsicum frutescens root cultures. Plant Physiol. Biochem. 2005, 43, 125-131.
35. Islek, C.; Ustun, A. S.; Koc, E. The effects of cellulase on capsaicin production in freely suspended cells and immobilized cell cultures of Capsicum annuum L. Pak. J. Bot. 2014, 46, 1883-1887.
36. Aggawwal, B. B. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem. Pharm. 2006, 71, 1397-1421.
37. Hanahan, D.; Weinberg, R. A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646-674.
38. Johnson, W., Jr. 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. Int. J. Toxicol. 2007, 26, 3-106.
39. Oyagbemi, A. A.; Saba, A. B.; Azeez, O. I. Capsaicin: A novel chemopreventive molecule and its underlying molecular mechanisms of action. Indian J. Cancer 2010, 47, 53-58.
40. Oh, S. H.; Kim, Y. S.; Lim, S. C.; Hou, Y. F.; Chang, I. Y.; You, H. J. Dihydrocapsaicin (DHC), a saturated structural analog of capsaicin, induces autophagy in human cancer cells in a catalase regulated manner. Autophagy 2008, 4, 1009-1019.
41. Yang, J.; Luo, B.; Xu, G.; Li, T.; Chen, Y.; Zhang, T. Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways. Neoplasma 2013, 60, 364-372.
42. Lee, S. H.; Richardson, R. L.; Dashwood, R. H.; Baek, S. J. Capsaicin represses transcriptional activity of β-catenin in human colorectal cancer cells. J. Nutr. Biochem. 2012, 23, 646-655.
43. Lu, H. F.; Chen, Y. L.; Yang, J. S.; Yang, Y. Y.; Liu, J. Y.; Hsu, S. C.; Lai, K. C.; Chung, J. G. Antitumor activity of capsaicin on human colon cancer cells in vitro and colo 205 tumor xenografts in vivo. J. Agric. Food Chem. 2010, 58, 12999-13005.
44. 2+ productions and caspase-3 activation. Mutat. Res. 2006, 601, 71-82.
45. Chang, H. C.; Chen, S. T.; Chien, S. Y.; Kuo, S. J.; Tsai, H. T.; Chen, D. R. Capsaicin may induce breast cancer cell death through apoptosis-inducing factor involving mitochondrial dysfunction. Hum. Exp. Toxicol. 2011, 30, 1657-1665.
46. Thoennissen, N. H.; O'Kelly, J.; Lu, D.; Iwanski, G. B.; La, D. T.; Abbassi, S.; Leiter, A.; Karlan, B.; Mehta, R.; Koeffler, H. P. Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway. Oncogene 2010, 29, 285-296.
47. Dou, D.; Ahmad, A.; Yang, H.; Sarkar, F. H. Tumor cell growth inhibition is correlated with levels of capsaicin present in hot peppers. Nutr. Cancer 2011, 63, 272-281.
48. De Sa Junior, P. L.; Pasqualoto, K. F.; Ferreira, A. K.; Tavares, M. T.; Damiao, M. C.; de Azevedo, R. A.; Câmaraa, D. A. D.; Pereiraa, A.; de Souzaa, D. M.; Filho, R. P. RPF101, a new capsaicin-like analogue, disrupts the microtubule network accompanied by arrest in the G2/M phase, inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells. Toxicol. Appl. Pharmacol. 2013, 266, 385-398.
49. Ip, S. W.; Lan, S. H.; Lu, H. F.; Huang, A. C.; Yang, J. S.; Lin, J. P.; Huang, H. Y.; Lien, J. C.; Ho, C. C.; Chiu, C. F.; et al. Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress. Hum. Exp. Toxicol. 2011, 31, 539-549.
50. 2+ inflx. Toxicol. Appl. Pharmacol. 2012, 259, 87-95.
51. Sanchez, A. M.; Sanchez, M. G.; Malagarie-Cazenave, S.; Olea, N.; Diaz-Laviada, I. Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin. Apoptosis 2006, 11, 89-99.
52. Hail, N.; Lotan, R. Examining the role of mitochondrial respiration in vanilloid-induced apoptosis. J. Natl. Cancer Inst. 2004, 94, 1281-1292.
53. Mori, A.; Lehmann, S.; O'Kelly, J.; Kumagai, T.; Desmond, J. C.; Pervan, M.; McBride, W. H.; Kizaki, M.; Koeffler, H. P. Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells. Cancer Res. 2006, 66, 3222-3229.
54. Sánchez, A. M.; Martínez-Botas, J.; Malagarie-Cazenave, S.; Olea, N.; Vara, D.; Lasunción, M. A.; Díaz-Laviada, I. Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: A microarray study. Biochem. Biophys. Res. Commun. 2008, 372, 785-791.
55. Sánchez, A. M.; Malagarie-Cazenave, S.; Olea, N.; Vara, D.; Chiloeches, A.; Díaz-Laviada, I. Apoptosis induced by capsaicin in prostate PC-3 cells involves ceramide accumulation, neutral sphingomyelinase, and JNK activation. Apoptosis 2007, 12, 2013-2024.
56. 2+ and caspase-3 in capsaicin-induced apoptosis of human leukemia HL-60 cells. Anticancer Res. 2006, 26, 1965-1971.
57. Kim, M. Y. Nitric oxide triggers apoptosis in A375 human melanoma cells treated with capsaicin and resveratrol. Mol. Med. Rep. 2012, 5, 585-591.
58. Lin, C. H.; Lu, W. C.; Wang, C. W.; Chan, Y. C.; Chen, M. K. Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells. BMC Complement. Altern. Med. 2013, 13, 46.
59. Jun, H. S.; Park, T.; Lee, C. K.; Kang, M. K.; Park, M. S.; Kang, H. I.; Surh, Y. J.; Kim, O. H. Capsaicin induced apoptosis of B16-F10 melanoma cells through down-regulation of Bcl-2. Food Chem. Toxicol. 2007, 45, 708-715.
60. Bhutani, M.; Pathak, A. K.; Nair, A. S.; Kunnumakkara, A. B.; Guha, S.; Sethi, G.; Aggarwal, B. B. Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation. Clin. Cancer Res. 2007, 13, 3024-3032.
61. Zhang, R.; Humphreys, I.; Sahu, R. P.; Shi, Y.; Srivastava, S. K. In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis 2008, 13, 1465-1478.
62. Pramanik, K. C.; Boreddy, S. R.; Srivastava, S. K. Role of mitochondrial electron transport chain complexes in capsaicin mediated oxidative stress leading to apoptosis in pancreatic cancer cells. PLoS ONE 2011, 6, e20151.
63. Zhang, J. H.; Lai, F. J.; Chen, H.; Luo, J.; Zhang, R. Y.; Bu, H. Q.; Wang, Z.-H.; Lin, H.-H.; Lin, S.-Z. Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1. Oncol. Lett. 2013, 5, 43-48.
64. Huang, S. P.; Chen, J. C.; Wu, C. C.; Chen, C. T.; Tang, N. Y.; Ho, Y. T.; Lo, C.; Lin, J. P.; Chung, J. G.; Lin, J. G. Capsaicin-induced apoptosis in human hepatoma HepG2 cells. Anticancer Res. 2009, 29, 165-174.
65. Chen, X.; Tan, M.; Feng, B.; Zhao, Z.; Yang, K.; Hu, C.; Liao, N.; Wang, T.; Chen, D.; Xie, F.; et al. Inhibiting ROS-STAT3-dependent autophagy enhanced capsaicin-induced apoptosis in human hepatocellular carcinoma cells. Free Radic. Res. 2016, 7, 744-755.
66. Wang, H. M.; Chueh, P. J.; Chang, S. P.; Yang, C. L.; Shao, K. N. Effect of capsaicin on tNOX (ENOX2) protein expression in stomach cancer cells. Biofactors 2009, 34, 209-217.
67. Yang, Z. H.; Wang, X. H.; Wang, H. P.; Hu, L. Q.; Zheng, X. M.; Li, S. W. Capsaicin mediates cell death in bladder cancer T24 cells through reactive oxygen species production and mitochondrial depolarization. Urology 2010, 75, 735-741.
68. Brown, K. C.; Witte, T. R.; Hardman, W. E.; Luo, H.; Chen, Y. C.; Carpenter, A. B.; Lau, J. K.; Dasgupta, P. Capsaicin displays antiproliferative activity against human small cell lung cáncer in cell culture and nude mice models via the E2F pathway. PLoS ONE 2010, 5, e10243.
69. Díaz-Labada, I. Effect of capsaicin on prostate cancer cells. Future Oncol. 2010, 6, 1545-1550.
70. Arnab, S.; Bhattacharjee, S.; Mandal, D. P. Induction of Apoptosis by Eugenol and Capsaicin in Human Gastric Cancer AGS Cells-Elucidating the Role of p53. Asian Pac. J. Cancer Prev. 2015, 16, 6753-6759.
71. Shin, D. H.; Kim, O. H.; Jun, H. S.; Kang, M. K. Inhibitory effect of capsaicin on B16-F10 melanoma cell migration via the phosphatidylinositol 3-kinase/Akt/Rac1 signal pathway. Exp. Mol. Med. 2008, 40, 486-494.
72. Bola, P. D.; Letali, A. Mitochondria-Judges and Executioners of Cell Death Sentences. Mol. Cell 2016, 61, 695-704.
73. Suhr, Y. J. More than spice: Capsaicin in hot chili peppers makes tumor cells commit suicide. J. Natl. Cancer Inst. 2002, 94, 1263-1265.
74. Ito, K.; Nakazato, T.; Yamato, K.; Miyakawa, Y.; Yamada, T.; Hozumi, N.; Segawa, K.; Ikeda, Y.; Kizaki, M. 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. Cancer Res. 2004, 64, 1071-1078.
75. Caprodossi, S.; Amantini, C.; Nabissi, M.; Morelli, B.; Farfariello, V.; Santoni, M.; Gismondi, A.; Santoni, G. Capsaicin promotes a more aggressive gene expression phenotype and invasiveness in null-TRPV1 urothelial cancer cells. Carcinogenesis 2011, 32, 686-694.
76. Reyes-Escogido, M. L.; Gonzalez-Mondragon, E. G.; Vazquez-Tzompantzi, E. Chemical and Pharmacological Aspects of Capsaicin. Molecules 2011, 16, 1253-1270.
77. Vercelli, C.; Barbero, R.; Cuniberti, B.; Odore, R.; Re, G. Expression and functionality of TRPV1 receptor in human MCF-7 and canine CF.41 cells. Vet. Comp. Oncol. 2013, 3, 77-155.
78. Prevarskaya, N.; Zhang, L.; Barritt, G. TRP channels in cancer. Biochim. Biophys. Acta 2007, 1772, 937-946.
79. Yang, K. M.; Pyo, J. O.; Kim, G. Y.; Yu, R.; Han, I. S.; Ju, S. A.; Kim, W. H.; Kim, B. S. Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell lines. Cell. Mol. Biol. Lett. 2009, 14, 497-510.
80. Datta, P.; Pramanik, K. C.; Mehrotra, S.; Srivastava, S. K. Capsaicin Mediated Oxidative Stress in Pancreatic Cancer. In Cancer, Oxidative Stress and Dietary Antioxidants, 1st ed.; Preedy, V., Ed.; Elsevier: London, UK, 2014; pp. 241-246.
81. Beltran, J.; Ghosh, A. K.; Basu, S. Immunotherapy of tumors with neuroimmune ligand capsaicin. J. Immunol. 2007, 178, 3260-3264.
82. Athanasiou, A.; Smith, P. A.; Vakilpour, S.; Kumaran, N. M.; Turner, A. E.; Bagiokou, D.; Layfield, R.; Ray, D. E.; Westwell, A. D.; Alexander, S. P. H.; et al. Vanilloid receptor agonists and antagonists are mitochondrial inhibitors: How vanilloids cause non-vanilloid receptor mediated cell death. Biochem. Biophys. Res. Commun. 2007, 354, 50-55.
83. Hail, N.; Lotan, R. Cancer chemoprevention and mitochondria: Targeting apoptosis in transformed cells via the disruption of mitochondrial bioenergetics/redox state. Mol. Nutr. Food Res. 2009, 53, 49-67.
84. Sinha, K.; Das, J.; Pal, P. B.; Sil, P. C. Oxidative stress: The mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch. Toxicol. 2013, 87, 1157-1180.
85. Kuhajda, F. P. AMP-activated protein kinase and human cancer: Cancer metabolism revisited. Int. J. Obes. 2008, 32, S36-S41.
86. Kim, Y. M.; Hwang, J. T.; Kwak, D. W.; Lee, Y. K.; Park, O. J. Involvement of AMPK signaling cascade in capsaicin-induced apoptosis of HT-29 colon cancer cells. Ann. N. Y. Acad. Sci. 2007, 1095, 496-503.
87. Hardie, D. G.; Alessi, D. R. LKB1 and AMPK and the cancer-metabolism link-ten years after. BMC Biol. 2013, 11, 36-47.
88. Chen, D.; Yang, Z.; Wang, Y.; Zhu, G.; Wang, X. Capsaicin induces cycle arrest by inhibiting cyclin-dependent-kinase in bladder carcinoma cells. Int. J. Urol. 2012, 19, 662-668.
89. Maity, R.; Sharma, J.; Jana, N. R. Capsaicin induces apoptosis through ubiquitin-proteasome system dysfunction. J. Cell Biochem. 2010, 109, 933-942.
90. Park, S. Y.; Kim, J. Y.; Lee, S. M.; Jun, C. H.; Cho, S. B.; Park, C. H.; Joo, Y. E.; Kim, S. H.; Choi, S. K. Capsaicin induces apoptosis and modulates MAPK signaling in human gastric cancer cells. Mol. Med. Rep. 2014, 9, 499-502.
91. Yoon, J. H.; Ahn, S. G.; Lee, B. H.; Jung, S. H.; Oh, S. H. Role of autophagy in chemoresistance: Regulation of the ATM-mediated DNA-damage signaling pathway through activation of DNAPKcs and PARP-1. Biochem. Pharmacol. 2012, 83, 747-757.
92. Chou, C. C.; Wu, Y. C.; Wang, Y. F.; Chou, M. J.; Kuo, S. J.; Chen, D. R. Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway. Oncol. Rep. 2009, 21, 665-671.