Studies on the tumor invasion through JAK2-STATs pathway inhibition by ginsenoside 20(S)-Rh2 in human colorectal cancer cells

Abstract

Ginsenoside Rh2 has been reported to inhibit cancer cell growth and induce apoptosis. The Rh2 has two stereoisomeric forms, 20(S) and 20(R) that have been reported different biological activities. 20(S)-Rh2 mainly has been focused of its anti-cancer and anti-inflammatory effects. However, it is poorly understood whether 20(S)-Rh2 and 20(R)-Rh2 can suppress tumor invasion in human colorectal cancer cells. Here, this study demonstrated that 20(S)-Rh2 strongly inhibited IL-6-induced signal transducer and activator of transcription 3 (STAT3) activation than that of 20(R)-Rh2. 20(S)-Rh2 inhibited STAT3 activation in HCT116 cells when cells were incubated with or without IL-6 stimulation. In addition, this compound effectively inhibited the levels of matrix metalloproteinases (MMPs), including MMP-1, -2, -3 and -9 that are known to be regulated by STAT3, resulting in suppression of the tumor cell invasion in colorectal cancer cells. In parallel, the expression levels of MMPs and tumor cell invasion were suppressed by siSTAT3. The pharmacological activities of 20(S)-Rh2 were identified to be associated with inhibition of the STAT3 upstream regulator JAK2 activation. Interestingly, these inhibitory activities of 20(S)-Rh2 were more potent than those of 20(R)-Rh2. This study further found that 20(S)-Rh2 synergistically enhanced cytotoxicity of HCT116 cells in combinational treatment with other anti-cancer agents, suggesting ginsenoside 20(S)-Rh2 has a promising therapeutic potential against colorectal tumor metastasis as well as to be a combinational partner with classic chemotherapeutic agents in treatment of colorectal cancer.