Phenethyl Isothiocyanate Inhibits Nasopharyngeal Carcinoma Cell Growth and Invasion
Journal of Diseases and Medicinal Plants
Volume 5, Issue 1, February 2019, Pages: 10-16
Received: Jan. 4, 2019;
Accepted: Jan. 23, 2019;
Published: Feb. 15, 2019
Views 233 Downloads 39
Chenggang Mao, Department of Otolaryngology–Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jinzhou, China
Xiaochun Zhou, Department of Otolaryngology–Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jinzhou, China
Yidao Jiang, Department of Otolaryngology–Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jinzhou, China
Lijia Wan, Department of Otolaryngology–Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jinzhou, China
Zezhang Tao, Department of Otolaryngology–Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China
The dietary compound phenethyl isothiocyanate (PEITC), is an active component of cruciferous vegetables and markedly inhibits the growth of a variety of tumors. However, its role in human nasopharyngeal carcinoma (NPC) is obscure. The aim of the present study was to elucidate the possible mechanisms whereby PEITC exhibited anticancer properties in human nasopharyngeal carcinoma NPC-TW01 cells in vitro. The experiment results exhibited that in a dose- and time-dependent manner treatment of NPC-TW01 cells with PEITC significantly inhibited cell proliferation, promoted apoptosis with concurrent G2/M cell cycle arrest and inhibited cell invasion in a dose-dependent manner. These effects were accompanied by significant alterations in the expression levels of key proteins associated with pro-survival signaling pathways, including PI3K, Akt, ERK, NF-κB, Bcl, Bax, cyclin B, CDK4 and CDK6. Significantly, these effects were not reflected in 16HBE normal human bronchial epithelial cells, indicating a safe range of treatment concentrations between 0 and 10 μM PEITC. In conclusion, PEITC exhibited significant anticancer effects against human nasopharyngeal carcinoma cells in vitro with low toxicological impact on normal bronchial epithelial cells. This was achieved through dysregulation of key proteins involved in the occurrence and development of tumors, and this approach may be applied to the clinical treatment of NPC and in drug screening.
Phenethyl Isothiocyanate Inhibits Nasopharyngeal Carcinoma Cell Growth and Invasion, Journal of Diseases and Medicinal Plants.
Vol. 5, No. 1,
2019, pp. 10-16.
Brennan B: Nasopharyngeal carcinoma. Orphanet J Rare Dis 1: 23, 2006.
Afqir S, Ismaili N and Errihani H: Concurrent chemoradiotherapy in the management of advanced nasopharyngeal carcinoma: current status. J Cancer Res Ther 5: 3 7, 2009.
Razak AR, Siu LL, Liu FF, Ito E, O'Sullivan B and Chan K: Nasopharyngeal carcinoma: the next challenges. Eur J Cancer 46: 1967 1978, 2010.
Zhou JX, Han JB, Chen SM, Xu Y, Kong YG, Xiao BK and Tao ZZ: γ secretase inhibition combined with cisplatin enhances apoptosis of nasopharyngeal carcinoma cells. Exp Ther Med 3: 357 361, 2012.
Kolonel LN, Hankin JH, Whittemore AS, Wu AH, Gallagher RP, Wilkens LR, John EM, Howe GR, Dreon DM, West DW, et al: Vegetables, fruits, legumes and prostate cancer: A multiethnic case-control study. Cancer Epidemiol Biomarkers Prev 9: 795-804, 2000.
Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell 144: 646-674, 2011.
Annema N, Heyworth JS, McNaughton SA, Iacopetta B and Fritschi L: Fruit and vegetable consumption and the risk of proximal colon, distal colon, and rectal cancers in a case-control study in Western Australia. J Am Diet Assoc 111: 1479-1490, 2011.
Gupta P, Kim B, Kim SH and Srivastava SK: Molecular targets of isothiocyanates in cancer: Recent advances. Mol Nutr Food Res 58: 1685-1707, 2014.
Trachootham D, Zhou Y, Zhang H, Demizu Y, Chen Z, Pelicano H, Chiao PJ, Achanta G, Arlinghaus RB, Liu J, et al: Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell 10: 241-252, 2006.
Huong D, Shim JH, Choi KH, Shin JA, Choi ES, Kim HS, Lee SJ, Kim SJ, Cho NP and Cho SD: Effect of β-phenylethyl isothiocyanate from cruciferous vegetables on growth inhibition and apoptosis of cervical cancer cells through the induction of death receptors 4 and 5. J Agric Food Chem 59: 8124-8131, 2011.
Sakao K, Desineni S, Hahm ER and Singh SV: Phenethyl isothiocyanate suppresses inhibitor of apoptosis family protein expression in prostate cancer cells in culture and in vivo. Prostate 72: 1104-1116, 2012.
Chan ATC: Nasopharyngeal carcinoma. Ann Oncol 21 (Suppl 7): vii308-vii312, 2010.
Teo PM, Kwan WH, Lee WY, Leung SF, Johnson PJ (1996) Prognosticators determining survival subsequent to distant metastasis from nasopharyngeal carcinoma. Cancer 77: 2423–2431.
Sham JS, Choy D, Choi PH (1990) Nasopharyngeal carcinoma: the significance of neck node involvement in relation to the pattern of distant failure. Br J Radiol 63: 108–113.
Ma BB, Chan AT (2005) Recent perspectives in the role of chemotherapy in the management of advanced nasopharyngeal carcinoma. Cancer 103: 22–31.
Huong LD, Shin JA, Choi ES, Cho NP, Kim HM, Leem DH and Cho SD: β-Phenethyl isothiocyanate induces death receptor 5 to induce apoptosis in human oral cancer cells via p38. Oral Dis 18: 513-519, 2012.
Wang XF, Wu DM, Li BX, Lu YJ and Yang BF: Synergistic inhibitory effect of sulforaphane and 5-fluorouracil in high and low metastasis cell lines of salivary gland adenoid cystic carcinoma. Phytother Res 23: 303-307, 2009.
Gupta P and Srivastava SK: Antitumor activity of phenethyl isothiocyanate in HER2-positive breast cancer models. BMC Med 10: 80, 2012.
Chen G, Chen Z, Hu Y and Huang P: Inhibition of mitochondrial respiration and rapid depletion of mitochondrial glutathione by β-phenethyl isothiocyanate: Mechanisms for anti-leukemia activity. Antioxid Redox Signal 15: 2911-2921, 2011.
Doerfler W, Hohlweg U, Müller K, Remus R, Heller H and Hertz J: Foreign DNA integration - perturbations of the genome - oncogenesis. Ann NY AcadSci 945:276-288, 2001.
Liu SF, Wang H, Lin XC, Xiang H, Deng XY, Li W, Tang M and Cao Y: NF-kappaB inhibitors induce lytic cytotoxicity in Epstein-Barr virus-positive nasopharyngeal carcinoma cells. Cell Biol Int 32: 1006-1013, 2008.
Wang YQ, Chen C, Chen Z, Xu Y, Wang Y, Xiao BK, Chen SM and Tao ZZ: Indole-3-carbinol inhibits cell proliferation and induces apoptosis in Hep-2 laryngeal cancer cells. Oncol Rep 30: 227-233, 2013.
Gupta P, Adkins C, Lockman P and Srivastava SK: Metastasis of breast tumor cells to brain is suppressed by phenethyl isothiocyanate in a novel in vivo metastasis model. PLoS One 8: e67278, 2013.
Newman DJ and Cragg GM: Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75: 311-335, 2012.
Singh SV, Kim SH, Sehrawat A, Arlotti JA, Hahm ER, Sakao K, Beumer JH, Jankowitz RC, Chandra-Kuntal K, Lee J, et al: Biomarkers of phenethyl isothiocyanate-mediated mammary cancer chemoprevention in a clinically relevant mouse model. J Natl Cancer Inst 104: 1228-1239, 2012.
Manesh C and Kuttan G: Effect of naturally occurring isothiocyanates on the immune system. Immunopharmacol Immunotoxicol 25: 451-459, 2003.
Wang LG and Chiao JW: Prostate cancer chemopreventive activity of phenethyl isothiocyanate through epigenetic regulation (Review). Int J Oncol 37: 533-539, 2010.