Ginsenoside Rh2 inhibiting HCT116 colon cancer cell proliferation through blocking PDZ-binding kinase/T-LAK cell-originated protein kinase.

Background: Ginsenoside Rh2 (GRh2) is the main bioactive component in American ginseng, a commonly used herb, and its antitumor activity had been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in HCT116 colorectal cancer cells.

Methods: We examined the effect of GRh2 on HCT116 cells . Next, we performed binding assay and kinase assay to search for the target of GRh2. Furthermore, we elucidated the underlying molecular mechanisms for the antitumor effect of GRh2 and .

Results: The results of our studies indicated that GRh2 can directly bind with PBK/TOPK and GRh2 also can directly inhibit PBK/TOPK activity. studies showed that GRh2 significantly induced cell death in HCT116 colorectal cancer cells. Further mechanistic study demonstrated that these compounds inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 (ERK1/2) and (H3) in HCT116 colorectal cancer cells. studies showed GRh2 inhibited the growth of xenograft tumors of HCT116 cells and inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 and histone H3.

Conclusion: The results indicate that GRh2 exerts promising antitumor effect that is specific to human HCT116 colorectal cancer cells through inhibiting the activity of PBK/TOPK.