Bhushan, Shashi and Kumar, Ajay and Malik, Fayaz and Andotra, Samar Singh and Sethi, Vijay Kumar and Kaur, Indu Pal and Taneja, Subhash Chandra and Qazi, Ghulam Nabi and Singh, Jaswant (2007) A triterpenediol from Boswellia serrata induces apoptosis through both the intrinsic and extrinsic apoptotic pathways in human leukemia HL-60 cells. Apoptosis, 12 (10). pp. 1911-1926. ISSN 1360-8185

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Abstract

A triterpenediol (TPD) comprising of isomeric mixture of 3a, 24-dihydroxyurs-12-ene and 3a, 24-dihydroxyolean-12-ene from Boswellia serrata induces apoptosis in cancer cells. An attempt was made in this study to investigate the mechanism of cell death by TPD in human leukemia HL-60 cells. It inhibited cell proliferation with IC50 ~ 12 lg/ml and produced apoptosis as measured by various biological end points e.g. increased sub-G0 DNA fraction, DNA ladder formation, enhanced AnnexinV-FITC binding of the cells. Further, initial events involved massive reactive oxygen species (ROS) and nitric oxide (NO) formation, which were significantly inhibited by their respective inhibitors. Persistent high levels of NO and ROS caused Bcl-2 cleavage and translocation of Bax to mitochondria, which lead to loss of mitochondrial membrane potential (Dwm) and release of cytochrome c, AIF,Smac/DIABLO to the cytosol. These events were associated with decreased expression of survivin and ICAD with attendant activation of caspases leading to PARP cleavage.Furthermore, TPD up regulated the expression of cell death receptors DR4 and TNF-R1 level, leading to caspase-8 activation. These studies thus demonstrate that TPD produces oxidative stress in cancer cells that triggers selfdemise by ROS and NO regulated activation of both the intrinsic and extrinsic signaling cascades.

Item Type:	Article
Subjects:	Pharmacological Sciences
Divisions:	UNSPECIFIED
Depositing User:	Mr. Amit Nargotra
Date Deposited:	19 Dec 2011 08:15
Last Modified:	19 Dec 2011 08:15
URI:	http://iiim.csircentral.net/id/eprint/197

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