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 α (ERα)-positive
breast cancer cells (ZR-75-30 and MCF-7) than ERα-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 ERα expression and inhibited membrane ERα-mediated
mitogen-activated protein kinase (MAPK) signaling following the stimulation of cells with
estrogen. Knockdown of ERα by
siRNA transfection in ZR-75-30 cells attenuated
HMQ1611 effects. In contrast, overexpression of ERα in MDA-MB-231 cells enhanced
HMQ1611 effects, suggesting that ERα pathway mediated
HMQ1611's inhibition of
breast cancer cell growth in ERα-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 ERα and/or EGFR signaling pathways, suggesting that
HMQ1611 may be a potential novel candidate for human
breast cancer intervention.