7α-Hydroxy-β-Sitosterol fromChisocheton tomentosusInduces Apoptosis via Dysregulation of Cellular Bax/Bcl-2 Ratio and Cell Cycle Arrest by Downregulating ERK1/2 Activation

Abstract

In continuation of our interest towards the elucidation of apoptotic pathways of cytotoxic phytocompounds, we have embarked upon a study on the anticancer effects of 7α-hydroxy-β-sitosterol (CT1), a rare natural phytosterol oxide isolated from Chisocheton tomentosus. CT1 was found to be cytotoxic on three different human tumor cell lines with minimal effects on normal cell controls, where cell viability levels were maintained ≥80% upon treatment. Our results showed that cell death in MCF-7 breast tumor cells was achieved through the induction of apoptosis via downregulation of the ERK1/2 signaling pathway. CT1 was also found to increase proapoptotic Bax protein levels, while decreasing anti-apoptotic Bcl-2 protein levels, suggesting the involvement of the intrinsic pathway. Reduced levels of initiator procaspase-9 and executioner procaspase-3 were also observed following CT1 exposure, confirming the involvement of cytochrome c-mediated apoptosis via the mitochondrial pathway. These results demonstrated the cytotoxic and apoptotic ability of 7α-hydroxy-β-sitosterol and suggest its potential anti-cancer use particularly on breast adenocarcinoma cells.

Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53/p21 and mitochondrial signalling pathway

“…Overexpression of Bcl-2 protein inhibits apoptosis whereby up-regulation of Bax protein induces apoptosis in the cancer cells (Mohan et al, 2012;Wu et al, 2012;Ng et al, 2011). Outcome of cellular viability/apoptosis is determined not only by the expression of specific pro-and anti-apoptotic genes/ proteins, but is dependent on the ratio between pro and anti-apoptotic proteins (Kumar et al, 2013;Tasyriq et al, 2012;Gao and Dou, 2000). In the present study, DCM-DS significantly increased the Bax/Bcl-2 ratio at the protein level ( Fig.…”

Puerarin Suppress Apoptosis of Human Osteoblasts via ERK Signaling Pathway

“…Extracellular signal-regulated kinase (ERK1/2), located at both the cytoplasm and the nucleus of cells, is a multifunctional serine/threonine kinases which induce various of substrates phosphorylation localized in all cellular compartments [33, 34]. It is believed that ERK is involved mainly in the activation of nuclear transcription factors that control cell proliferation, differentiation and apoptosis [35].…”

Protective Effect of CpG-Oligodeoxynucleotides Against Low- and High-LET Irradiation

“…As shown in Fig. 6A, Bax expression was upregulated, Bcl-2 expression was downregulated, and the ratio of Bax/Bcl-2, which is considered to be one of the major markers of apoptosis, was also increased [20]. Caspase-3 expression was increased, and cleaved caspase-3 protein appeared after γ-ray and carbon-beam irradiation.…”