Glaucocalyxin A Activates FasL and Induces Apoptosis Through Activation of the JNK Pathway in Human Breast Cancer Cells

This study was conducted to analyze the molecular mechanisms responsible for anti-proliferation effects ofglaucocalyxin A in cultured MCF-7 and Hs578T breast cancer cells. The concentration that reduced cell viabilityto 50% (IC50) after 72 h treatment was derived and potential molecular mechanisms of anti-proliferationusing the IC50 were investigated as changes in cell cycle arrest and apoptosis. Gene and protein expressionchanges related to apoptosis were investigated by semi-quantitative RT-PCR and western blotting, respectively.Involvement of phosphorylated mitogen-activated protein kinases and JNK signaling in regulation of thesemolecules was characterized by western blotting. Cell viability decreased in a concentration-dependent mannerand the IC50 was determined as 1μM in MCF-7 and 4μM in HS578T cell. Subsequently, we demonstrated thatthe GLA-induced MCF-7 and Hst578T cell death was due to cell cycle arrest at the G2/M transition and wasassociated with activation of the c-jun N-terminal kinase (JNK) pathway. We conclude that GLA has the potentialto inhibit the proliferation of human breast cancer cells through the JNK pathway and suggest its applicationforthe effective therapy for patients with breast cancer.