Synthetic Triterpenoid Cyano Enone of Methyl Boswellate Activates Intrinsic, Extrinsic, and Endoplasmic Reticulum Stress Cell Death Pathways in Tumor Cell Lines

Ravanan, Palaniyandi and Sano, Renata and Talwar, Priti and Ogasawara, Satoshi and Matsuzawa, Shu-ichi and Cuddy, Michael and Singh, Sanjay K and Rao, Subba GSR and Kondaiah, Paturu and Reed, John C (2011) Synthetic Triterpenoid Cyano Enone of Methyl Boswellate Activates Intrinsic, Extrinsic, and Endoplasmic Reticulum Stress Cell Death Pathways in Tumor Cell Lines. In: Molecular Cancer Therapeutics, 10 (9). pp. 1635-1643.

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Abstract

We explored the effect of a novel synthetic triterpenoid compound cyano enone of methyl boswellates (CEMB) on various prostate cancer and glioma cancer cell lines. CEMB displayed concentration-dependent cytotoxic activity with submicromolar lethal dose 50% (LD(50)) values in 10 of 10 tumor cell lines tested. CEMB-induced cytotoxicity is accompanied by activation of downstream effector caspases (caspases 3 and 7) and by upstream initiator caspases involved in both the extrinsic (caspase 8) and intrinsic (caspase 9) apoptotic pathways. By using short interfering RNAs (siRNA), we show evidence that knockdown of caspase 8, DR4, Apaf-1, and Bid impairs CEMB-induced cell death. Similar to other proapoptotic synthetic triterpenoid compounds, CEMB-induced apoptosis involved endoplasmic reticulum stress, as shown by partial rescue of tumor cells by siRNA-mediated knockdown of expression of genes involved in the unfolded protein response such as IRE1 alpha, PERK, and ATF6. Altogether, our results suggest that CEMB stimulates several apoptotic pathways in cancer cells, suggesting that this compound should be evaluated further as a potential agent for cancer therapy. Mol Cancer Ther; 10(9); 1635-43. (C)2011 AACR.

Item Type:	Journal Article
Publication:	Molecular Cancer Therapeutics
Publisher:	American Association for Cancer Research
Additional Information:	Copyright of this article belongs to American Association for Cancer Research.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	28 Sep 2011 11:15
Last Modified:	28 Sep 2011 11:15
URI:	http://eprints.iisc.ac.in/id/eprint/40772

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