A Novel Taspine Derivative, HMQ1611, Inhibits Breast Cancer Cell Growth via Estrogen Receptor α and EGF Receptor Signaling Pathways

作者：Zhan, Yingzhuan; Zhang, Yanmin; Liu, Cuicui; Zhang, Jie; Smith, Wanli W.; Wang, Nan; Chen, Yinnan; Zheng, Lei; He, Langchong^*

来源：Cancer Prevention Research, 2012, 5(6): 864-873.

DOI：10.1158/1940-6207.CAPR-11-0575

• LUNG-CANCER
• ACTIVATION
• MECHANISMS
• EXPRESSION
• HORMONE
• ASSOCIATION
• ESTRADIOL
• BIOLOGY
• GENE
• SHC

Breast cancer is a common cancer with a leading cause of cancer mortality in women. Currently, the chemotherapy for breast cancer is underdeveloped. Here, we report a novel taspine derivative, HMQ1611, which has anticancer effects using in vitro and in vivo breast cancer models. HMQ1611 reduced cancer cell proliferation in four human breast cancer cell lines including MDA-MB-231, SK-BR-3, ZR-75-30, and MCF-7. HMQ1611 more potently reduced growth of estrogen receptor alpha (ER alpha)-positive breast cancer cells (ZR-75-30 and MCF-7) than ER alpha-negative cells (MDA-MB-231 and SK-BR-3). Moreover, HMQ1611 arrested breast cancer cell cycle at S-phase. In vivo tumor xenograft model, treatment of HMQ1611 significantly reduced tumor size and weight compared with vehicles. We also found that HMQ1611 reduced ERa expression and inhibited membrane ER alpha-mediated mitogen-activated protein kinase (MAPK) signaling following the stimulation of cells with estrogen. Knockdown of ER alpha by siRNA transfection in ZR-75-30 cells attenuated HMQ1611 effects. In contrast, overexpression of ER alpha in MDA-MB-231 cells enhanced HMQ1611 effects, suggesting that ER alpha pathway mediated HMQ1611's inhibition of breast cancer cell growth in ER alpha-positive breast cancer. HMQ1611 also reduced phosphorylation of EGF receptor (EGFR) and its downstream signaling players extracellular signal-regulated kinase (ERK)1/2 and AKT activation both in ZR-75-30 and MDA-MB-231 cells. These results showed that the novel compound HMQ1611 had anticancer effects, and partially via ER alpha and/or EGFR signaling pathways, suggesting that HMQ1611 may be a potential novel candidate for human breast cancer intervention. Cancer Prev Res; 5(6); 864-73.

• 出版日期2012-6
• 单位西安交通大学