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14-Deoxy-11,12-didehydroandrographolide inhibits proliferation and induces GSH-dependent cell death of human promonocytic leukemic cells

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Abstract

14-Deoxy-11,12-didehydroandrographolide (AND2), an analogue of andrographolide, showed more potent cytotoxicity against human promonocytic leukemia (THP-1) cells than adherent cancer cell lines. In this study AND2 was isolated from the plant Andrographis paniculata and it was characterized. The antiproliferative effect of AND2 on both adherent (PC-3 and MDAMB) and non-adherent (THP-1 and Jurkat) cancer cell lines was evaluated by MTT assay. The effect of intracellular reduced glutathione (GSH) on AND2-induced cytotoxicity was studied by conducting cell viability assays on GSH-pretreated cells. The effect of AND2 on the redox status of THP-1 cells was determined by analyzing the endogenous reduced GSH content. Apoptosis induction was confirmed by DNA laddering assay and Western blot analysis using anti-caspase-3 protein antibody. AND2 showed antiproliferative action on both THP-1 and Jurkat cancer cell lines with low IC50 values. Cytotoxicity of AND2 was reversed by GSH pretreatment. AND2 treatment decreased the GSH content by 19.76 % (p < 0.001) in the THP-1 cancer cell line and reduced the cell clumping between the THP-1 cells. Expression of procaspase-3 varied in THP-1 cells during the time course of AND2 treatment. Procaspase-3 expression reached a maximum in treated cells at 32 h and was markedly reduced at 48 h but no procaspase-3 cleavage was observed. The obtained results suggest that AND2 is more effective against leukemia cells. AND2 induced a redox-mediated cell death in THP-1 cells. As AND2 temporarily increased the procaspase-3 expression during treatment, this study encourages the preclinical testing of AND2 against promonocytic leukemia cells in combination with small molecules that directly activate procaspase-3 to caspase-3.

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Acknowledgments

We acknowledge Dr. Sibabratha Mukhopadhyay, CSIR-Indian Institute of Chemical Biology, for the advices on NMR spectrum assignments. We acknowledge the Council for Scientific and Industrial Research (CSIR) for senior research fellowship, File No. 9/43(0163) 2KI3-EMRI. We acknowledge the Department of Biotechnology, India and University of Calicut for providing research facilities.

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  1. Department of Biotechnology, University of Calicut, Calicut University P.O., Malappuram district, Kerala, 673635, India

    Rahul Raghavan, Sanith Cheriyamundath & Joseph Madassery

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  1. Rahul Raghavan
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  3. Joseph Madassery
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Correspondence to Joseph Madassery.

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Raghavan, R., Cheriyamundath, S. & Madassery, J. 14-Deoxy-11,12-didehydroandrographolide inhibits proliferation and induces GSH-dependent cell death of human promonocytic leukemic cells. J Nat Med 68, 387–394 (2014). https://doi.org/10.1007/s11418-014-0815-2

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