Triacontanoic ester of 5''-hydroxyjustisolin: Tumour suppressive role in cervical cancer via Bcl-2, BAX and caspase-3 mediated signalling

Litty Joseph; K K Srinivasan

doi:10.1016/j.toxrep.2019.10.015

Triacontanoic ester of 5''-hydroxyjustisolin: Tumour suppressive role in cervical cancer via Bcl-2, BAX and caspase-3 mediated signalling

Toxicol Rep. 2019 Oct 31:6:1198-1205. doi: 10.1016/j.toxrep.2019.10.015. eCollection 2019.

Authors

Litty Joseph¹, K K Srinivasan²

Affiliations

¹ Department of Pharmaceutical Sciences, Centre for Professional and Advanced studies, Cheruvandoor Campus, Ettumanoor PO, Kottayam, 686 631, Kerala, India.
² Department of Chemistry, Shri Madhwa Vadiraja Institute of Technology and Management, Bantakal, Udupi, 574 115, Karnataka, India.

Abstract

Triacontanoic ester of 5"-hydroxyjustisolin, a lignan from Justicia simplex D. Don, possesses antitumor activity. However, the molecular mechanism underlying this is not yet clearly understood. The present study showed significant inhibition in cell viability on HeLa cell line and induced minor toxicity in normal cells. This compound induced mitotic arrest at G0/G1 phase followed by apoptosis in human cervical cancer cells and was accompanied by the upregulation of BAX, caspase-3 and downregulation of Bcl-2. Taken together, these data reveal that the title compound acts through multiple cellular/molecular pathways, which strongly suggest the role of pro and antiapoptotic Bcl-2 family proteins. Triacontanoic ester of 5''-hydroxyjustisolin may be a potential agent for the cervical cancer treatment.

Keywords: Antitumor; BAX; Bcl-2; Caspase-3; DLA, Daltons lymphoma ascites; DMEM, Dulbecco's modified eagle's medium; DMSO, dimethyl suphoxide; FBS, fetal bovine serum; HaCat, human keratinocyte immortalised; HeLa, human cervical carcinoma; Justicia simplex D. Don; MCF-7, human breast adenocarcinoma cell line; MTT, methyl tetrazolium assay; RT-PCR, reverse transcriptase polymerize chain reaction; TE5-OHJ, triacontanoic ester of 5ʹʹ-hydroxyjustisolin; Triacontanoic ester of 5ʺ -hydroxyjustisolin.