Benzoin Thiosemicarbazone Inhibits Growth and Triggers Apoptosis in Earlich Ascites Carcinoma Cells through an Intrinsic Pathway

Abstract

Anticancer drug development is now an emerging field of research all over the world. In this study we attempt to synthesize a novel, simple, inexpensive and safe chemical agents Benzoin thiosemicarbazone (BTSC) and studied against Ehrlich Ascites Carcinoma (EAC) cells bearing Swiss Albino mice by monitoring in vivo tumor cell growth inhibition, survival time of tumor bearing swiss albino mice. MTT colorimetric assay was done to assess the in vitro effect of the test compound. The intrinsic apoptotic pathway induced by BTSC was evidenced by p53 or tumor protein, B-cell lymphoma 2 (BCL-2), B-cell lymphoma extra-large (BCL-xL), BCL-2 associated X protein (BAX), cleavage of caspase-9 and caspase-3 and poly-ADP ribose polymerase (PARP-1). Reactive oxygen species (ROS) generation after BTSC treatment was determined by 2´, 7´- dicholorodihydrofluorescein diacetate (DCFH-DA) staining. The compound was found to possess pronounced anticancer effect. Maximum cell growth inhibition, enhancement of life span was found 73.53% and 52.17% at the dose of 8 mg/kg (i.p) respectively. The induction of apoptosis by BTSC occurred through an ROS-dependent mitochondria-mediated intrinsic pathway rather than an extrinsic pathway, and was regulated by the BCL-2 protein family. The compound exerted a potent antitumor effect toward Ehrlich ascites carcinoma cells through the induction of apoptosis via an intrinsic pathway. Thus, this study provides evidence to carry out further researches in a way to formulate novel anticancer drugs.