NF-κB Down–regulation and PARP Cleavage by novel 3-α-butyryloxy-β-boswellic Acid Results in Cancer Cell Specific Apoptosis and in vivo Tumor Regression

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


Volume 16, 12 Issues, 2016


Download PDF Flyer




Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 27th of 59 in Chemistry, Medicinal

Submit Abstracts Online Submit Manuscripts Online

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


View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.722
5 - Year: 2.849

NF-κB Down–regulation and PARP Cleavage by novel 3-α-butyryloxy-β-boswellic Acid Results in Cancer Cell Specific Apoptosis and in vivo Tumor Regression



Anti-Cancer Agents in Medicinal Chemistry, 13(5): 777-790.

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.

Affiliation: Cancer Pharmacology Division, Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi 180001 India.

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-α-Butyryloxy-β-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 β-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 (ΛΨm) 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-κB 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.

Keywords:

DNA repair, Apoptosis, Cancer, Natural Products, Drug, Signaling, PI3K, Boswellia serrata.



Purchase Online Order Reprints Order Eprints Rights and Permissions




Article Details

Volume: 13
Issue Number: 5
First Page: 777
Last Page: 790
Page Count: 14
DOI: 10.2174/1871520611313050012
Price: $58
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2016 Bentham Science