NFkB Down-regulation and PARP Cleavage by Novel 3-?-Butyryloxy-?-boswellic Acid Results in Cancer Cell Specific Apoptosis and in vivo Tumor Regression

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 14, 10 Issues, 2014


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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  • 22nd of 58 in Chemistry, Medicinal
  • 85th of 202 in Oncology

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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NFkB Down-regulation and PARP Cleavage by Novel 3-?-Butyryloxy-?-boswellic Acid Results in Cancer Cell Specific Apoptosis and in vivo Tumor Regression

Author(s): Yasrib Qurishi, Abid Hamid, Parduman R. Sharma, Zahoor A. Wani, Dilip M. Mondhe, Shashank K. Singh, Mohmmad A. Zargar, Samar S. Andotra, Bhahwal A. Shah, Subhash C. Taneja and Ajit K. Saxena


Abstract

The present study relates to the induction of apoptosis thereof cytotoxicity and anti-cancer activity displayed by semi-synthetic analog of Boswellic acid i.e. 3-?-Butyryloxy-?-boswellic acid (BOBA). The cytotoxicity data revealed the differential sensitivity of cancer cell lines towards BOBA which may display its impact against different types of cancers. Considering the inhibitory potential of BOBA, we further sought to understand the target for BOBA deciphering the mechanism of action leading to apoptotic cell death and it was for the first time reported about the triterpenoid ring especially the ?-boswellic acid derivative is targeting PI3K pathway. Our data revealed that BOBA treatment provides evidence about the apoptotic nature showing the potential of targeting mitochondria dependent pathways during apoptosis in HL-60 cells. BOBA induced hypo-diploid sub-G1 DNA population in HL-60 cells as was also evident from the pattern of DNA fragmentation and mitochondrial membrane potential (??m) loss. Morphological analysis under fluorescent and scanning electron microscopy displayed typical features such as cell shrinkage, membrane blebbing, chromatin condensation and nuclear fragmentation. These events paralleled with the down-regulation of NF-?B and induced PARP cleavage. Furthermore, it is noteworthy that BOBA also depicted significant growth inhibition in Ehrlich Ascitic Tumour (EAT), Ehrlich Ascitic Carcinoma (EAC) and Sarcoma-180 tumour models. Taken together, BOBA treatment may represent as potential agent to the currently available anticancer agents in both prophylactic and/or therapeutic applications. Also, our findings may open up a new perspective in the construction of novel anticancer agents based on boswellic acids that will facilitate the development of these agents for anticancer therapeutics.


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Article Details

Volume: 13
First Page: 1
Last Page: 1
Page Count: 1
DOI: 10.2174/18715206113139990108
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