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Potentiation of the antitumor effect of 11-keto-β-boswellic acid by its 3-α-hexanoyloxy derivative

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Title Potentiation of the antitumor effect of 11-keto-β-boswellic acid by its 3-α-hexanoyloxy derivative
 
Creator Chashoo, Gousia
Singh, Shashank K.
Mondhe, Dilip M.
Sharma, Parduman R.
Andotra, Samar S.
Shah, Bhahwal.A.
Taneja, Subhash C.
Saxena, Ajit K.
 
Subject Pharmacological Sciences
 
Description We recently discovered that a propionyloxy derivative of 11-keto-β-boswellic acid (PKBA) showed better anticancer potential than other boswellic acids including AKBA, encompassing the importance of acyl group at the 3-α-hydroxy position of KBA. In continuation of our previous work, other higher derivatives (with increasing alkoxy chain length at 3-α-hydroxy position) including butyryloxy (BKBA) and hexanoyloxy(HKBA) derivatives of KBA were synthesized. The respective IC50 values of BKBA and HKBA in HL-60 cells were found to be 7.7 and 4.5 μg/ml. IC50 value of HKBA was comparatively lower than that of BKBA, and further lower than that of the previously reported derivative (PKBA, IC50 8.7 μg/ml). In order to compare the anticancer potential of HKBA with PKBA, detailed in vitro pro-apoptotic and in vivo anticancer studies were carried out. The induction of apoptosis by HKBA was measured using various parameters including
fluorescence and scanning electron microscopy, DNA fragmentation and Annexin V-FITC binding. The extent
of DNA damage was measured using neutral comet assay. HKBA was further evaluated for its effect on DNA cell cycle and mitochondria where it was found to arrest cells in G2/M phase and also induced loss of mitochondrial membrane potential. These events were associated with increased expression of cytosolic cytochrome c and cleavage of PARP. Target based studies showed that HKBA inhibited the enzymatic activity of topoisomerases I and II at low doses than that of PKBA. In vivo studies also revealed a low dose inhibitory effect of HKBA on ascitic and solid murine tumor models.
 
Date 2011
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://iiim.csircentral.net/314/1/10.1016j.ejphar.2011.07.024.pdf
Chashoo, Gousia and Singh, Shashank K. and Mondhe, Dilip M. and Sharma, Parduman R. and Andotra, Samar S. and Shah, Bhahwal.A. and Taneja, Subhash C. and Saxena, Ajit K. (2011) Potentiation of the antitumor effect of 11-keto-β-boswellic acid by its 3-α-hexanoyloxy derivative. European Journal of Pharmacology, 668 (3). pp. 390-400. ISSN 00142999
 
Relation http://dx.doi.org/10.1016/j.ejphar.2011.07.024
http://iiim.csircentral.net/314/