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Mechanism of apoptotic induction in human breast cancer cell, MCF-7, by an analog of curcumin in comparison with curcumin - An in vitro and in silico approach.
MedLine Citation:
PMID:  24365254     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In Developing countries, survival rates for breast cancer are poor and it accounts for 22.9% of all cancers in women. Curcumin, a major constituent from turmeric, is one of the well-known chemopreventive agents. Reports have shown that curcumin induces apoptosis in breast cancer cells. We synthesized an ortho-hydroxy substituted analog of curcumin (BDMC-A) and analyzed its cytotoxicity. The BDMC-A inhibited MCF-7 at a dose equivalent to that of curcumin (30 μM). The present study was aimed at delineating the apoptotic mechanism of BDMC-A in comparison to that of curcumin. In our study, BDMC-A exerted more potent effect on the modulation of selective apoptotic markers (intrinsic pathway: p53, Bcl-2, Bax, cyt c, Apaf-1, caspase-9, 3, PARP; extrinsic pathway: FasL, Caspase 8) compared to curcumin. mRNA expression studies for Bcl2/Bax also supported the increased efficacy of BDMC-A. An in silico molecular docking study with PI3K revealed that the docking of BDMC-A was more potent compared to curcumin. Increased apoptotic induction by BDMC-A compared to curcumin was also demonstrated by Annexin V, Rh123(ΔΨm), PI, Hoechst 33258, AO/EB fluorescent staining studies which showed characteristic apoptotic features like nuclear fragmentation and chromatin condensation. Moreover, BDMC-A treated cells effectively induced apoptosis through ROS intermediates compared to curcumin, as measured by 2'-7'dichloro dihydro fluorescein diacetate (DCFH-DA). Hence our overall results showed that BDMC-A induced apoptosis more effectively compared to curcumin and the activity can be attributed to the presence of hydroxyl group in the ortho position in its structure. Further researches are going on to delineate its molecular targets to evaluate its effect as a potent anticancer agent.
Authors:
Kumaravel Mohankumar; Sankar Pajaniradje; Subhashree Sridharan; Vivek Kumar Singh; Larance Ronsard; Akhil C Banerjea; Chellakkan S Benson; Mohane Selvaraj Coumar; Rukkumani Rajagopalan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-20
Journal Detail:
Title:  Chemico-biological interactions     Volume:  -     ISSN:  1872-7786     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier Ireland Ltd.
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