A study on inhibition mechanism of breast cancer cells by bis-type triaziquone.
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.
Lin
Yuh-Ling
YL
School of Medicine, Fu Jen University, Taipei, Taiwan.
Su
Yi-Ting
YT
Chen
Bing-Huei
BH
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D013997:Time Factors; D014228:Triaziquone / Q000494:pharmacology*
D018906:Antineoplastic Agents, Alkylating; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D014228:Triaziquone