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

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• 作者：Jianjun Yang¹ ; ^☆ ; Donghong Yuan¹ ; ^☆ ; Tongchao Xing² ; Hongli Su³ ; Shengjun Zhang⁴ ; Jiansheng Wen⁵ ; ^{wenjiansheng1965@126.com" class="auth_mail" title="E-mail the corresponding author} ; Qiqiang Bai⁶ ; ^{baiqiqiang369@126.com" class="auth_mail" title="E-mail the corresponding author} ; Dongmei Dang⁷ ; ^{dangdongmei263@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：antitumor effect ; apoptosis ; ginsenoside Rh2 ; HCT116 colorectal cancer cells ; PDZ-binding kinase/T-LAK cell-originated protein kinase
• 刊名：Journal of Ginseng Research
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：40
• 期：4
• 页码：400-408
• 全文大小：1629 K

文摘

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 ex vivo. Next, we performed in vitro binding assay and in vitro kinase assay to search for the target of GRh2. Furthermore, we elucidated the underlying molecular mechanisms for the antitumor effect of GRh2 ex vivo and in vivo.

Results

The results of our in vitro studies indicated that GRh2 can directly bind with PBK/TOPK and GRh2 also can directly inhibit PBK/TOPK activity. Ex vivo 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. In vivo 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.