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

Abstract

BackgroundGinsenoside 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.MethodsWe 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.ResultsThe 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.ConclusionThe results indicate that GRh2 exerts promising antitumor effect that is specific to human HCT116 colorectal cancer cells through inhibiting the activity of PBK/TOPK.

Atractylenolide I Induces Apoptosis and Suppresses Glycolysis by Blocking the JAK2/STAT3 Signaling Pathway in Colorectal Cancer Cells

“…Moreover, STAT3 overexpression significantly attenuated the AT-Iinduced inhibition of glycolysis and apoptosis. For in vivo experiments, we used HCT116 xenograft model, which has a high sensitivity to drug stimulation (He et al, 2016;Yang et al, 2016;Zhang et al, 2017). As reported previously, AT-I presented anticancer activity at a concentration of 25 to 75 mg/kg (Yu et al, 2016).…”

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…F. H. Chen, Panax ginseng and Cinnamomum cassia Presl., with various biological effects including anti-oxidative, anti-inflammatory, and anti-cancer activities [219][220][221][222]. Ginsenosides mainly exert anti-cancer effects in colorectal, breast, liver and lung cancers, through inhibiting cell proliferation and migration, angiogenesis, and reversing drug resistance [7,[223][224][225][226][227][228][229][230]. Ginsenoside Rg3, ginsenoside Rh2, and compound K are the primary bioactive compounds among ginsenosides for cancer prevention.…”

Chinese Herbal Medicine and Its Regulatory Effects on Tumor Related T Cells

“…Important herbs that have been studied with regard to BUFA include Radix astragalus (huang qi), and its ability to enhance the immune system (Denzer et al, 2006); Atractylodes rhizome (bai zhu), which increases lymphocyte proliferation and stimulates the immune system (Son et al, 2017); and Radix codonopsis (dang shen), which increases red blood cells and assists in T cell formation (He et al, 2015b). Additionally, American ginseng or Panacis quinquefolii radix (xi yang shen) has been found to inhibit cancer of the liver (Qu et al, 2018), colon (Yang et al, 2016), and breast cancer (Yonghe, 2004).…”