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

Abstract

This study was conducted to analyze the molecular mechanisms responsible for anti-proliferation effects of glaucocalyxin A in cultured MCF-7 and Hs578T breast cancer cells. The concentration that reduced cell viability to 50% (IC50) after 72 h treatment was derived and potential molecular mechanisms of anti-proliferation using the IC50 were investigated as changes in cell cycle arrest and apoptosis. Gene and protein expression changes 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 these molecules was characterized by western blotting. Cell viability decreased in a concentration-dependent manner and the IC50 was determined as 1 μΜ in MCF-7 and 4 μΜ in Hs578T cell. Subsequently, we demonstrated that the GLA-induced MCF-7 and Hst578T cell death was due to cell cycle arrest at the G2/M transition and was associated with activation of the c-jun N-terminal kinase (JNK) pathway. We conclude that GLA has the potential to inhibit the proliferation of human breast cancer cells through the JNK pathway and suggest its application forthe effective therapy for patients with breast cancer.

Mechanistic Pathways and Molecular Targets of Plant-Derived Anticancer ent-Kaurane Diterpenes

“…It also upregulated the expression of extrinsic apoptotic markers such as Fas and Fas ligand (FasL) at the mRNA and protein level. Moreover, the expression of p-ERK and p-JNK increased in a dose-dependent manner after glaucocalyxin A treatment [58]. Furthermore, it concentration-dependently suppressed the proliferation and induced apoptosis in human brain glioblastoma U87MG cells by activating caspase-3, while downregulating p-Akt, p-Bad, and X-linked inhibitor of apoptosis protein (XIAP) [59].…”

Comparative transcriptome analysis of roots, stems and leaves of Isodon amethystoides reveals candidate genes involved in Wangzaozins biosynthesis

“…Pharmacological studies have identified the bioactivities of Wangzaozins. For example, glaucocalyxin A has been widely studied for certain important biological activities, including antitumor [ 11 ], apoptosis induction [ 12 , 13 ], antibacterial, anti-oxidative, anticoagulative, antithrombotic, antifibrotic, immune, and antineuroinflammatory activities [ 5 , 14 , 15 ]. Wangzaozin A, specifically isolated from Wang Zao Zi and not from other Isodon species, has been proved to be effective in the treatment of pneumonia, lung abscess, and pulmonary tuberculosis when applied independently.…”

Reactive oxygen species mediate oridonin-induced apoptosis through DNA damage response and activation of JNK pathway in diffuse large B cell lymphoma

“…Hu et al showed that bufalin induced growth inhibition and apoptosis in hepatocellular carcinoma cells via JNK activation [26]. Li et al also found that glaucocalyxin A induced apoptosis through activation of the JNK pathway in human breast cancer cells [27]. In accordance with these earlier reports, we found that treatment with oridonin increased the expressions of p-JNK and p-p38, but only the JNK inhibitor SP600125 could inhibit oridonin-induced activation of caspase-3 and caspase-9, demonstrating that JNK may play a major role in promoting oridonin-induced apoptosis in DLBCL.…”