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

Content Provider	PubMed Central
Author	Saha, Suchandrima Ghosh, Monisankar Dutta, Samir Kumar
Copyright Year	2015
Abstract	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.
Related Links	http://dx.doi.org/10.1038/srep07762
Starting Page	7762
File Format	PDF
ISSN	20452322
e-ISSN	20452322
Journal	Scientific Reports
Volume Number	5
Language	English
Publisher	Nature Publishing Group
Publisher Date	2015-01-14
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Science and technology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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