Ferulago angulata activates intrinsic pathway of apoptosis in MCF-7 cells associated with G1 cell cycle arrest via involvement of p21/p27

Abstract

Ferulago angulata is a medicinal plant that is traditionally known for its anti-inflammatory and antiulcer properties. The present study was aimed to evaluate its anticancer activity and the possible mechanism of action using MCF-7 as an in vitro model. F. angulata leaf extracts were prepared using solvents in the order of increasing polarity. As determined by MTT assay, F. angulata leaves hexane extract (FALHE) revealed the strongest cytotoxicity against MCF-7 cells with the half maximal inhibitory concentration (IC50) value of 5.3±0.82 μg/mL. The acute toxicity study of FALHE provided evidence of the safety of the plant extract. Microscopic and flow cytometric analysis using annexin-V probe showed an induction of apoptosis in MCF-7 by FALHE. Treatment of MCF-7 cells with FALHE encouraged the intrinsic pathway of apoptosis, with cell death transducing signals that reduced the mitochondrial membrane potential with cytochrome c release from mitochondria to cytosol. The released cytochrome c triggered the activation of caspase-9. Meanwhile, the overexpression of caspase-8 suggested the involvement of an extrinsic pathway in the induced apoptosis at the late stage of treatment. Moreover, flow cytometric analysis showed that FALHE treatment significantly arrested MCF-7 cells in the G1 phase, which was associated with upregulation of p21 and p27 assessed by quantitative polymerase chain reaction. Immunofluorescence and the quantitative polymerase chain reaction analysis of MCF-7 cells after treatment with FALHE revealed an upregulation of Bax and a downregulation of Bcl-2 proteins. These findings proposed that FALHE suppressed the proliferation of MCF-7 cells via cell cycle arrest and the induction of apoptosis through intrinsic pathway.

Diallyl trisulfide induces osteosarcoma cell apoptosis through reactive oxygen species-mediated downregulation of the PI3K/Akt pathway

“…Overexpression of cyclin D1 is known to correlate with the risk of tumor progression (29). The p21 and p27 genes have recently been discovered to be important cyclin-dependent kinase inhibitors (CDKIs) and regulate the cell cycle as well as DNA replication and repair (30). Our results found that the expression of cyclin D1 was decreased whereas levels of p21 and p27 were upregulated.…”

Chemopreventive Activity of Ferulago angulate against Breast Tumor in Rats and the Apoptotic Effect of Polycerasoidin in MCF7 Cells: A Bioassay-Guided Approach

“…In our previous investigation, F . angulata leaf hexane extract (FALHE) was found to induce apoptosis in MCF7 cells via a mitochondrial-dependent pathway and cell cycle arrest [ 15 ]. Thus, the aims of the present study were to examine the in vivo chemopreventive effect of FALHE against LA7-induced breast tumors in rats and to investigate polycerasoidin as a cytotoxic compound and its underlying mechanism of action using a bioassay-guided approach.…”

In Vitro and In Vivo Anticancer Activity of the Most Cytotoxic Fraction of Pistachio Hull Extract in Breast Cancer

“…This study explained the potential use of red Pistacia vera hull as chemopreventive drug, as it can be exploited as a new lead compound for prodrug therapy. Since MCF7 is an estrogen-receptor negative human breast cancer, it's good for potential future examination of our extract and its active compound in another estrogen receptor-responsive cell line like MDA-231 [23]. Also as extracts of plants may activate the immune system of the hosts and kill cancer cells, one can consider testing the concentrations of various cytokines, tumor necrosis factor, etc.…”