Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Dietary isothiocyanate sulforaphene induces reactive oxygen species, caspase -9, -8, -3-dependent apoptosis and modulates PTEN/PI3Kinase in human cervical cancer cells

Yun-Hee Rhee¹, Arindam Mondal¹, Phil-Sang Chung^1,2, Jin-Chul Ahn^1,3

¹Beckman Laser Institute Korea; ²Laser Translational Clinical Trial Center; ³Department of Biomedical Science, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea.

For correspondence:- Jin-Chul Ahn Email: jcahn@dankook.ac.kr Tel:+82415503889

Accepted: 28 November 2017 Published: 29 December 2017

Citation: Rhee Y, Mondal A, Chung P, Ahn J. Dietary isothiocyanate sulforaphene induces reactive oxygen species, caspase -9, -8, -3-dependent apoptosis and modulates PTEN/PI3Kinase in human cervical cancer cells. Trop J Pharm Res 2017; 16(12):2811-2821 doi: 10.4314/tjpr.v16i12.4

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the apoptotic activity, cell proliferation inhibition and different signaling protein expressions after treatment with a new isothiocyanate, sulforaphene, in human cervical cancer (HeLa) cells.

Methods: Cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after sulforaphene treatment for 3, 6, 12 and 24 h. Apoptosis assay, cell cycle analysis, intracellular oxygen species (ROS) measurement, mitochondrial membrane depolarization and western blot analysis were performed in four time-intervals to explore sulforaphene activity.

Results: HeLa cell viability was reduced by sulforaphene dose and time dependently. ROS plays a causative role in sulforaphene induced cytotoxicity and apoptosis during which stimulation of Bax and blocking of Bcl2 were involved. Mitochondrial membrane potential depletion and cytochrome C, AIF modulation suggest mitochondrial pathway for the apoptosis. Activation of caspase -9, -8 and -3 in treated HeLa cells demonstrated caspase-dependent apoptosis by sulforaphene. Again, sulforaphene induced HeLa cell proliferation inhibition was evidenced by cell cycle arrest and PTEN/PI3Kinase modulation.

Conclusion: Dietary sulforaphene induces HeLa cell apoptosis by enhancing intracellular ROS levels, thereby activating multiple apoptotic signal cascades. Therefore, sulforaphene is a potential candidate for anticancer therapy

Keywords: Sulforaphene, HeLa cells, Apoptosis, ROS, Caspase activation, PTEN, PI3Kinase