(I-3,II-3)-Biacacetin-mediated cell death involves mitochondria

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 biflavonoid (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 0.5 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 (25 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 15 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 25 μM. Taken together, these results provide an understanding of biacacetin-mediated cell death and thereby provides a strong basis for the use of such compounds as novel templates for anti-cancer therapeutics.

Systematic understanding of anti-tumor mechanisms of Tamarixetin through network and experimental analyses

“…3D spheroid culture. Liquid overlay method was employed for spheroid generation 80 . 96 well plates were coated with 1.5% agarose.…”

Visible-Light Mediated Radical Alkylation of Flavones: A Modular Access to Nonsymmetrical 3,3″-Biflavones

“…Among these dimers is a small subgroup of two flavone units joined by a carbon–carbon bond at the C-3 position, called biflavones I-3, II-3 (or 3, 3″). A representative member of this subgroup is Biapigenin 1 (Figure ), a nonzinc-dependent gelatinase inhibitor (MMP-2 and MMP-9) for potential cancer therapy. Despite this potential application, the study of these types of molecules has remained relatively unexplored, probably due to their limited natural occurrence, and the scarcity of efficient synthetic methods .…”

“…In 2011, Sagrera and Seoane reported the dimerization of 3-iodoflavones 2 through an Ullman coupling reaction. Nanjan and Banjeri used the dimerization of 1,3-diketones 3 in a CAN-mediated radical coupling reaction to obtain symmetrical biflavones. , Interestingly, to our knowledge, no synthetic approaches for nonsymmetric biflavones have been reported to date. Furthermore, these previously described strategies involve high temperatures or strong oxidants, which limits their application.…”