Ginsenoside Rb1 promotes PC12 cell cycle kinetics through an adenylate cyclase–dependent protein kinase A pathway

Abstract

Ginsenoside Rb1 (G-Rb1), a constituent of ginseng, bears various beneficial effects on neuroendocrine cells. Previous studies have indicated that G-Rb1 can enhance glutamate release in undifferentiated and differentiated PC12 cells via the protein kinase A (PKA)-dependent signaling pathway. We hypothesized that G-Rb1 stimulates rat adrenomedullary chromaffin cell line PC12 (PC12 cells) proliferation and mitosis by promoting the cell cycle at all regulatory points. This mechanism is partly mediated via the adenylate cyclase-dependent PKA signaling pathway. In the present study, we investigated the mechanism by which G-Rb1 promotes cell cycle kinetics from the PC12 cells. The cell cycle kinetics of these cells were determined using flow cytometric DNA analysis. Analysis of the PC12 cell cycle revealed that G-Rb1 may affect all phases of the cell cycle and accelerate cell cycle kinetics by stimulating G0G1 phase transiting to S and G2M phases. The cell cycle kinetics were decreased by coincubating with the adenylate cyclase inhibitor SQ22536. Compared with the G-Rb1-treated group, the PKA inhibitor H89 produced a marked decrease in the G-Rb1-stimulated cell cycle kinetics by inhibiting G0G1 phase from transiting to the S phase. These results support the position that G-Rb1 exerts a stimulatory effect on cell cycle kinetics to promote PC12 cell proliferation. The result also suggests that the division rate is mediated via the adenylate cyclase-dependent PKA signaling pathway.