Identification of 7-(4′-Cyanophenyl)indoline-1-benzenesulfonamide as a mitotic inhibitor to induce apoptotic cell death and inhibit autophagy in human colorectal cancer cells

Tung Yun Wu, Ting Yu Cho, Chung Kuang Lu, Jing Ping Liou, Mei Chuan Chen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Targeting cellular mitosis in tumor cells is an attractive cancer treatment strategy. Here, we report that B220, a synthetic benzenesulfonamide compound, could represent a new mitotic inhibitor for the treatment of colorectal cancer. We examined the action mechanism of B220 in the colorectal carcinoma HCT116 cell line, and found that treatment of cells with B220 caused cells to accumulate in G2/M phase, with a concomitant induction of the mitotic phase markers, MPM2 and cyclin B1. After 48 h of B220 treatment, cells underwent apoptotic cell death via caspase-3 activation and poly(ADP ribose) polymerase (PARP) cleavage. In addition, B220 inhibits autophagy by blocking conversion of microtubule-associated protein 1 light chain 3 (LC3-I) to LC3-II and inhibiting autophagic flux. Notably, blockade of autophagy by pharmacological inhibition or using an Atg5-targeting shRNA reduced B220-induced cytotoxicity. Conversely, the autophagy inducer NVP-BEZ235 shows a synergistic interaction with B220 in HCT116 cells, indicating autophagy was required for the observed cell death. In summary, these results indicate B220 combined with the induction of autophagy using the dual PI3K/mTOR inhibitor, NVP-BEZ235, might be an attractive strategy for cancer therapy, and provides a framework for further development of B220 as a new therapeutic agent for colon cancer treatment.

Original languageEnglish
Article number12406
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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