Record Details

A potent tumoricidal co-drug ‘Bet-CA’ - an ester derivative of betulinic acid and dichloroacetate selectively and synergistically kills cancer cells

EPrints@IICB

View Archive Info
 
 
Field Value
 
Title A potent tumoricidal co-drug ‘Bet-CA’ - an ester derivative of betulinic acid and dichloroacetate selectively and synergistically kills cancer cells
 
Creator Saha, Suchandrima
Ghosh, Monisankar
Dutta, Samir Kumar
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description Selective targeting of cancer cells employing multiple combinations as co-drug holds promise for new generation therapeutics. Betulinic acid (BA), a plant secondary metabolite kills cancer cells and Dichloroacetate (DCA) is capable of reversing the Warburg phenotype by inhibiting pyruvate dehydrogenase kinase (PDK). Here, we report synthesis, characterization and tumoricidal potential of a co-drug Bet-CA, where a DCA molecule has been appended on C-3 hydroxyl group of BA to generate an ester derivative for increased solubility and subsequent cleavage by internal esterase(s) to release one unit each of BA and DCA. In vitro studies revealed pronounced synergistic cytotoxicity of Bet-CA against a broad spectrum of cancer cells and it selectively killed them when co-cultured with human fibroblasts. Bet-CA treatment increased reactive oxygen species (ROS) production, significantly altered mitochondrial membrane potential gradient (ΔΨm); followed by the release of cytochrome c (Cyt c) which prompted cells to undergo mitochondria mediated apoptosis. In vivo experimentation expectedly exhibited tumor inhibitory potential of Bet-CA and clinically achievable doses did not produce any apparent toxicity. Taken together, results suggestively raise an important corollary hypothesis stating that Bet-CA selectively and synergistically combats cancer without producing toxic manifestations and emerges to be the prospect for the new generation therapeutics
 
Date 2015
 
Type Article
PeerReviewed
 
Format application/msword
 
Identifier http://www.eprints.iicb.res.in/2257/1/SCIENTIFIC_REPORTS__V._5_____Article_Number_7762;2015[80].docx
Saha, Suchandrima and Ghosh, Monisankar and Dutta, Samir Kumar (2015) A potent tumoricidal co-drug ‘Bet-CA’ - an ester derivative of betulinic acid and dichloroacetate selectively and synergistically kills cancer cells. Scientific Reports, 5 (7762).
 
Relation htto://dx.doi.org/10.1038/srep07762
http://www.eprints.iicb.res.in/2257/