ArticleInvestigational new drugs2015
Acetylamine derivative of diospyrin, a plant-derived binaphthylquinonoid, inhibits human colon cancer growth in Nod-Scid mice.
Article in Investigational new drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors at 2 institutions in 1 country.
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Abstract
Anticancer activity of diospyrin and its derivatives (1-5) was evaluated against thirteen human cell lines. Compared to diospyrin (1), the acetylamine derivative (4) exhibited increase in cytotoxicity, particularly in HT-29 colon cancer cells, showing GI50 values of 33.90 and 1.96 μM, respectively. Also, enhanced toxicity was observed when cells, pre-treated with compound 4, were exposed to radiation. In vivo assessment of 4 was undertaken on tumour-bearing Nod-Scid mice treated at 4 mg/kg/day. Significant reduction in relative tumour volume (~86-91 %) was observed during the 12th-37th days after drug treatment. Increased caspase-3 activity and DNA ladder formation was observed in HT-29 cells after treatment with 4, suggesting induction of apoptotic death after drug treatment. Moreover, flow cytometric determination of Annexin V- FITC positive and PI negative cells demonstrated 17.4, 26.4, and 27.9 % of early apoptosis, respectively, upon treatment with 5, 10 and 25 μM of 4. HT-29 cells after treatment with 4 (1-25 μM) revealed ~2.5- 3- folds generation of ROS. Furthermore, concentration dependent decrease of mitochondrial trans-membrane potential (∆ψm), and expression of Bcl-2/Bax and other marker proteins suggested involvement of mitochondrial pathway of cell death. Overall, our results demonstrated the underlying cell-death mechanism of the plant-derived naphthoquinonoid (4), and established it as a prospective chemotherapeutic 'lead' molecule against colon cancer.
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