Inhibition of Lung Cancer Cell Proliferation and Activation of Apoptosis by Celastrol Triazole through JNK/ERK Pathway Up-Regulation

The present study investigated celastrol triazole as anti-proliferative agent against lung cancer cells and explored the underlying mechanism. Celastrol triazole treatment reduced viability of NCI-H1975 and H1299 cells significantly (p <0.05) in concentration dependent manner. Treatment of NCI-H1975 and H1299 cells with celastrol triazole reduced colony formation in significantly (p < 0.05) at 32 mu M compared to the control cells. Incubation with 32 mu M celastrol triazole increased apoptosis in NCI-H1975 and H1299 cells to 59.48 and 65.78%, respectively. Treatment with 32 mu M celastrol triazole led to a significant decrease in invasion potential of NCI-H1975 and H1299 cells. Celastrol triazole treatment led to a prominent increase in level of cleaved caspase-3 and expression of Bax protein in NCI-H1975 and H1299 cells. In celastrol triazole treated NCI-H1975 and H1299 cells a remarkable increase in phosphorylated-ERK and -JNK protein expression was observed at 72 h. Thus, celastrol triazole reduces viability of lung cancer cells by inducing activation of apoptosis through increase in pro-apoptotic protein expression. Moreover, it suppresses invasion and up-regulates phosphorylation of ERK/JNK proteins in NCI-H1975 and H1299 cells. Therefore, celastrol triazole may he studied further as anticancer agent for treatment for the lung cancer.