20(S)-ginsenoside Rh2 inhibits the proliferation and induces the apoptosis of KG-1a cells through the Wnt/β-catenin signaling pathway

Previous research has shown that total saponins of Panax ginseng (TSPG) and other ginsenoside monomers inhibit the proliferation of leukemia cells. However, the effect has not been compared among them. Cell viability was determined by Cell Counting Kit-8 assay, and ultra-structural characteristics were observed under transmission electron microscopy. Cell cycle distribution and apoptosis were determined by flow cytometry (FCM). Real-time fluorescence quantitative-PCR, western blotting and immunofluorescence were used to measure the expression of beta-catenin, TCF4, cyclin Dl and NF-KBp65. beta-catenin/TCF4 target gene transcription were observed by ChIP-PCR assay. We found that 20(S)-ginsenoside Rh2 [(S)Rh2] inhibited the proliferation of KG-la cells more efficiently than the other monomers. Moreover, (S)Rh2 arrested KG-la cells in the GO/G1 phase and induced apoptosis. In addition, the levels of beta-catenin, TCF4, cyclin D1 mRNA and protein were decreased. The ChIP-PCR showed that (S)Rh2 downregulated the transcription of beta-catenin/TCF4 target genes, such as cyclin Dl and c-myc. These results indicated that (S)Rh2 induced cell cycle arrest and apoptosis through the Wnt/beta-catenin signaling pathway, demonstrating its potential as a chemotherapeutic agent for leukemia therapy.