Sulfonoquinovosyl diacylglyceride selectively targets acute lymphoblastic leukemia cells and exerts potent anti-leukemic effects in vivo
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Sulfonoquinovosyl diacylglyceride selectively targets acute
lymphoblastic leukemia cells and exerts potent anti-leukemic effects in vivo
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| Creator |
Jain, Chetan Kumar
Pradhan, Bhola Shankar Banerjee, Sukdeb Mondal, Nirup Bikash Majumder, Subeer S Bhattacharyya, Madhumita Chkrabarti, Saikat Roychoudhury, Susanta Majumder, Hemanta Kumar |
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| Subject |
Cancer Biology and Inflammatory Disorder Division
Chemistry Infectious Diseases and Immunology Structural Biology & Bioinformatics |
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| Description |
DNA topoisomerase II inhibitors e.g. doxorubicin and etoposide are currently used in the chemotherapy for acute lymphoblastic leukemia (ALL). These inhibitors have serious side effects during the chemotherapy e.g. cardiotoxicity and secondary malignancies. In this study we show
that sulfonoquinovosyl diacylglyceride (SQDG) isolated from Azadirachta indica exerts potent anti-ALL activity both in vitro and in vivo in nude mice and it synergizes with doxorubicin and etoposide. SQDG selectively targets ALL MOLT-4 cells by inhibiting catalytic activity of topoisomerase I enzyme and inducing p53 dependent apoptotic pathway. SQDG treatment induces recruitment of ATR at chromatin and arrests the cells in S-phase. Down-regulation of topoisomerase I or p53 renders the cells less sensitive for SQDG, while ectopic expression of wild type p53 protein in p53 deficient K562 cells results in chemosensitization of the cells for SQDG. We also show that constant
ratio combinations of SQDG and etoposide or SDQG and doxorubicin exert synergistic effects on MOLT-4 cell killing. This study suggests that doses of etoposide/ doxorubicin can be substantially reduced by combining SQDG with these agents during ALL chemotherapy and side effects caused can be minimized. Thus dual targeting of topoisomerase I and II enzymes is a promising strategy for
improving ALL chemotherapy
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| Date |
2015
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| Type |
Article
PeerReviewed |
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| Format |
text/html
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| Identifier |
http://www.eprints.iicb.res.in/2386/1/Scientific_Reports.htm
Jain, Chetan Kumar and Pradhan, Bhola Shankar and Banerjee, Sukdeb and Mondal, Nirup Bikash and Majumder, Subeer S and Bhattacharyya, Madhumita and Chkrabarti, Saikat and Roychoudhury, Susanta and Majumder, Hemanta Kumar (2015) Sulfonoquinovosyl diacylglyceride selectively targets acute lymphoblastic leukemia cells and exerts potent anti-leukemic effects in vivo. Scientific Reports, 5. |
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| Relation |
http://dx.doi.org/10.1038/srep12082
http://www.eprints.iicb.res.in/2386/ |
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