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Induction of growth cessation by acacetin via β-catenin pathway and apoptosis by apoptosis inducing factor activation in colorectal carcinoma cells

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Abstract

Acacetin, a bioflavanoid, contains anti-inflammatory and anti-cancer activities as shown in different experimental models. However, its anticancer potential and mechanism of action against colorectal cancer cells is largely unknown. Here, we have investigated the efficacy of acacetin using two colorectal adenocarcinoma SW480 and HCT-116 cell lines. Cell survival was examined by Trypan-blue exclusion and MTT assays, cell cycle analysis by FACS, apoptosis was assessed using Annexin V FITC assay and nuclear condensation by Hoechst staining, ROS level by DCFDA and Mitosox, and protein expression level by Western blotting. Acacetin reduced the cell survival and proliferation of both types of cells, and induced S- and G2-M phase arrest and also reduced the levels of β-catenin and its downstream target c-myc. Further, acacetin induced apoptosis as examined by Annexin-V FITC and nuclear condensation. It increased intracellular ROS production, especially mitochondrial ROS. Acacetin increased mitochondrial membrane potential depolarization and Bax:Bcl-2 ratio. Although significant changes in caspases -8 and -9 and PARP level was not observed, acacetin could induce the truncation and subsequent translocation of activated AIF from mitochondria to cytosol, which could further induce chromosomal breakage leading to apoptosis. In conclusion, Acacetin induces mitochondrial ROS-mediated cell death in a caspase-independent manner in SW480 and HCT-116 colon carcinoma cells by inducing apoptosis inducing factor (AIF), which may potentiate its anticancer and chemotherapeutic prospects against colorectal carcinoma.

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Acknowledgments

NP is recipient of UGC Non-NET Fellowship from Central University of Gujarat, Gandhinagar, UCSY is recipient of Ramanujan Fellowship from Department of Science and Technology (DST), Govt of India.

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  1. Metabolic Disorder & Inflammatory Pathologies Laboratory, School of Life Sciences, Central University of Gujarat, Sector -30, Gandhinagar, 382030, Gujarat, India

    Nupoor Prasad, Jiten R. Sharma & Umesh C. S. Yadav

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  1. Nupoor Prasad
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  2. Jiten R. Sharma
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  3. Umesh C. S. Yadav
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Correspondence to Umesh C. S. Yadav.

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Prasad, N., Sharma, J.R. & Yadav, U.C.S. Induction of growth cessation by acacetin via β-catenin pathway and apoptosis by apoptosis inducing factor activation in colorectal carcinoma cells. Mol Biol Rep 47, 987–1001 (2020). https://doi.org/10.1007/s11033-019-05191-x

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