A Novel Resveratrol Based Tubulin Inhibitor Induces Mitotic Arrest and Activates Apoptosis in Cancer Cells

Thomas, Elizabeth and Gopalakrishnan, Vidya and Hegde, Mahesh and Kumar, Sujeet and Karki, Subhas S and Raghavan, Sathees C and Choudhary, Bibha (2016) A Novel Resveratrol Based Tubulin Inhibitor Induces Mitotic Arrest and Activates Apoptosis in Cancer Cells. In: SCIENTIFIC REPORTS, 6 .

PDF Sci_Rep_6_34653_2016.pdf - Published Version Download (1MB)

Abstract

Resveratrol is one of the most widely studied bioactive plant polyphenols which possesses anticancer properties. Previously we have reported synthesis, characterization and identification of a novel resveratrol analog, SS28. In the present study, we show that SS28 induced cytotoxicity in several cancer cell lines ex vivo with an IC50 value of 3-5 mu M. Mechanistic evaluation of effect of SS28 in non-small cell lung cancer cell line (A549) and T-cell leukemic cell line (CEM) showed that it inhibited Tubulin polymerization during cell division to cause cell cycle arrest at G2/M phase of the cell cycle at 12-18 h time period. Immunofluorescence studies confirmed the mitotic arrest upon treatment with SS28. Besides, we show that SS28 binds to Tubulin with a dissociation constant of 0.414 +/- 0.11 mu M. Further, SS28 treatment resulted in loss of mitochondrial membrane potential, activation of Caspase 9 and Caspase 3, leading to PARP-1 cleavage and finally cell death via intrinsic pathway of apoptosis. Importantly, treatment with SS28 resulted in regression of tumor in mice. Hence, our study reveals the antiproliferative activity of SS28 by disrupting microtubule dynamics by binding to its cellular target Tubulin and its potential to be developed as an anticancer molecule.

Item Type:	Journal Article
Publication:	SCIENTIFIC REPORTS
Additional Information:	Copy right for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	03 Dec 2016 06:45
Last Modified:	03 Dec 2016 06:45
URI:	http://eprints.iisc.ac.in/id/eprint/55320

Actions (login required)

View Item