Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biochanin A is a major isoflavone in red clover and a potent chemopreventive agent against cancer. However, the effects of biochanin A on human osteosarcoma cells have never been clarified. This study investigated the anti-proliferative potential of biochanin A in osteosarcoma cells. The results indicate that biochanin A inhibited cell growth and colony formation in a dose-dependent manner with a minimal toxicity to normal cells. The combination of doxorubicin and biochanin A could synergistically inhibit osteosarcoma cell growth. The cytotoxic effect of biochanin A via the induction of apoptosis as evidenced by formation of apoptotic bodies, externalization of phosphatidylserine, accumulation of sub-G1 phase cells, caspase 3 activation, and cleavage of PARP. Apoptosis was associated with loss of the mitochondrial membrane potential, release of cytochrome c, caspase 9 activation, increased Bax expression, and reduced Bcl-2 and Bcl-XL expression. Pre-treatment with a caspase-9 specific inhibitor (Z-LEHD-FMK) partially attenuated cell death, suggesting involvement of the intrinsic mitochondrial apoptotic cascade. However, pre-treatment with the JNK inhibitor SP600125, the MEK inhibitor PD-98059, and the p38 MAPK inhibitor SB203580 or the antioxidants vitamin E, N-acetylcysteine, and glutathione failed to prevent biochanin A-induced cell death. Our results suggest that biochanin A inhibits cell growth and induces apoptosis in osteosarcoma cells by triggering activation of the intrinsic mitochondrial pathway and caspase-9 and -3 and increasing the Bax: Bcl-2/Bcl-XL ratio.
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PMID:Anti-proliferative activity of biochanin A in human osteosarcoma cells via mitochondrial-involved apoptosis. 2930 28

Biochanin A has been reported to be associated to tumour cell proliferation, apoptosis and drug resistance in hepatocellular carcinoma, prostate cancer, and colorectal cancer, etc, while the relation of biochanin A on osteosarcoma is not clear. Hence, in this study, we examined the effects of biochanin A treatment on osteosarcoma cell lines MG63 and U2OS on proliferation, apoptosis, invasion and migration. We then investigated the involved molecular mechanism and found a time- and dose-dependent inhibition of cell viability in MG63 and U2OS cells with biochanin A treatment. Under the same circumstances, an increased ratio of cells in G0/G1 phase but a decreased ratio of cells in G2/M phase was observed. In addition, after biochanin A treatment, apoptotic rates clearly increased and decreased migration and invasion ability were observed in MG63 and O2OS cells. Meanwhile, relevant genes involved in cell proliferation, apoptosis, invation and migration demonstrated altered expressions in MG63 and U2OS cells. The present study supports the assumption that biochanin A has suppressive effects on osteosarcoma through regulating cell proliferation, apoptosis, invasion, and migration.
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PMID:The effect of biochanin A on cell growth, apoptosis, and migration in osteosarcoma cells. 2988 86