Abstract

Polygalacin D (PGD) is a bioactive compound isolated from Platycodon grandiflorum (Jacq.) and it has a similar structure to platycodinD, which is a well known anticancer agent. In the present study, we investigated the anti-proliferative effects of PGD using NSCLC cell lines. We evaluated the effects of PGD on proliferation, apoptosis and cell cycle arrest in A549 and H460 cells. PGD significantly induced apoptosis and nuclear condensation in both cell lines. Furthermore, PGD upregulated the cleavage of apoptotic proteins such as caspase-3, -9 and PARP. Additionally, treatment with PGD suppressed the expression of the IAP family of proteins including survivin, cIAP-1 and cIAP-2. Furthermore, PGD induced G0/G1-phase arrest in both cell lines. After treatment with PGD, the expression of TIMP-1, CDK2, cyclinA and cyclinE was reduced at the protein level. In addition, PGD blocked the PI3K/Akt pathway by inhibiting the phosphorylation of GSK3β, Akt and the expression of PI3K. Our results indicated that the anti-proliferative properties of PGD may result from the regulation of the PI3K/Akt pathway, which plays a critical role in cell survival and growth.

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