A study on inhibition mechanism of breast cancer cells by bis-type triaziquone

Abstract

The objectives of this study were to evaluate the antiproliferation effect of a synthetic quinone-containing compound bis-type triaziquone (BTZQ) on breast cancer cells BC-M1 and MCF-7. At a dose of 0.42 and 0.79 microM, BTZQ showed a 50% inhibition on BC-M1 and MCF-7 cell growth after 24 h treatment, respectively, but reduced to 0.2 and 0.61 microM after 48 h. A low toxic effect was observed for skin fibroblast cell after BTZQ treatment for 48 h at a dose from 0.0625-0.25 microM. BTZQ was more effective in inhibiting growth of breast cancer cells than tamoxifen. Additionally, BTZQ-treated BC-M1 cells under hypoxia condition for 48 h exhibited a higher cytotoxicity than under aerobic condition. Cell cycle analysis revealed the arrest of BC-M1 cells at G2/M phase, with accumulation of apoptotic cells at the sub-G1 phase being enhanced following a rise in dose. The expression levels of caspase-3, caspase-8 and caspase-9 were elevated in both dose- and time-dependent responses. Western blot analysis indicated that BTZQ may up-regulate expression of cyclin B, p21, p53 and cytochrome c, but down-regulate cdk1 expression in a dose-dependent manner, leading to apoptosis of BC-M1 cells. All these results suggested that BTZQ may be a potential anti-breast cancer drug.