Panaxydol Derived from Panax ginseng Inhibits G1 Cell Cycle Progression in Non-small Cell Lung Cancer via Upregulation of Intracellular Ca2+ Levels

Panaxydol, a polyacetylenic compound derived from Panax ginseng has been reported to suppress the growth of cancer cells. However, the molecular mechanisms underlying cell cycle arrest by this compound in non-small cell lung cancer (NSCLC) are unknown. Our study found that panaxydol treatment induced cell cycle arrest at G(1) phase in NSCLC cells. The cell cycle arrest was accompanied by down-regulation of the protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D-1 and cyclin E, and decrease in the phosphorylation of retinoblastoma (Rb) protein. Furthermore, up-regulation of cyclin-dependent kinase inhibitor (CDKI) p21(C1P1/WAF1) and p27(KIP1) was observed in panaxydol-treated NSCLC cells. In addition, panaxydol also induced accumulation of intracellular Ca2+ ([Ca2+](i)). (Acetyloxy)methyl 2-({2-[(acetyloxy)-methoxyl-2-oxoethyl}[2-(2-{2-[bis({2-Kacetyloxy)methoxyl-2-oxoethylpaminolphenoxylethoxy)phenyllamino)-acetate (BAPTA-AM), the Ca2+ chelator, attenuated not only panaxydol-induced accumulation of ICa2 1 but also G(1) cell cycle arrest and decrease of CDK6 and cyclin D-1 protein expression level. These results demonstrated that the anti-proliferative effects of panaxydol were caused by cell cycle arrest, which is closely linked to the up-regulation of [Ca2+](i), and represents a promising approach for the treatment of lung cancer.