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(I-3,II-3)-Biacacetin-mediated Cell Death involves Mitochondria

Publication Type : Journal Article

Publisher : Molecular and cellular biochemistry

Source : Molecular and cellular biochemistry, Volume 451, Issue (1-2), p.79-90 (2018)

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Keywords : apoptosis, Biacacetin, Cell death, Mitochondria.

Campus : Amritapuri

School : School of Biotechnology

Department : biotechnology

Year : 2018

Abstract : Dysregulation of the dynamic balance between cell proliferation and cell death leads to several malignancies including cancer. Biflavones are known to possess anti-proliferative activity against numerous cancer cell lines. The current study was undertaken to understand the mechanism of action of the biflavonoidnbsp;(I-3,II-3)-biacacetin on MDA-MB-231. Biacacetin induces dose-dependent cell death in MDA-MB-231 cells from concentrations as low as 0.5nbsp;μM, which was further confirmed by an increase in sub-G1 cells. Furthermore, the cell death induced by biacacetin was found to be mitochondria-dependent, since cells devoid of mitochondria were viable in the presence of biacacetin even at the highest concentration tested (25nbsp;μM). Fluorescence studies clearly indicated nuclear changes and apoptotic body formation that are characteristic of apoptosis. These results were further corroborated by studies that demonstrate biacacetin to regulate several key markers of apoptosis like Caspase 3, p53, Bax, and poly-ADP-ribose polymerase-1. Furthermore, biacacetin did not induce cell death in normal macrophage cell line, RAW at concentrations up to 15nbsp;μM. In addition to MDA-MB-231 cells, biacacetin also induces apoptotic cell death in the highly chemo-resistant cell line, OVISE, where the cells stained positive for annexin. Biacacetin also induces cell death in the highly malignant fibrosarcoma cell line HT1080. Furthermore, biacacetin also induces significant cell death (50%) in 3D tumor spheroids, at a concentration of 25nbsp;μM. Taken together, these results provide an understandingnbsp;of biacacetin-mediated cell death and thereby provides a strong basis for the use of such compounds as novel templates for anti-cancer therapeutics.

Cite this Research Publication : Jyotsna Nambiar, Gayathri Vijayakumar, G. Drishya, Sanu K Shaji, Nanjan Pandurangan, Geetha B. Kumar, and Dr. Bipin G. Nair, “(I-3,II-3)-Biacacetin-mediated cell death involves mitochondria.”, Molecular and cellular biochemistry, 2018

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