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 β-catenin, TCF4, cyclin D1 and NF-κBp65. β-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-1a cells more efficiently than the other monomers. Moreover, (S)Rh2 arrested KG-1a cells in the G0/G1 phase and induced apoptosis. In addition, the levels of β-catenin, TCF4, cyclin D1 mRNA and protein were decreased. The ChIP-PCR showed that (S)Rh2 downregulated the transcription of β-catenin/TCF4 target genes, such as cyclin D1 and c-myc. These results indicated that (S)Rh2 induced cell cycle arrest and apoptosis through the Wnt/β-catenin signaling pathway, demonstrating its potential as a chemotherapeutic agent for leukemia therapy.
Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, P.R. China.
Yi
Y
Chen
Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, P.R. China.
Ze-Hong
ZH
Liu
Department of Human Anatomy, Chongqing Medical and Health School, Chongqing 408000, P.R. China.
Jing
J
Xia
Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, P.R. China.
Xiao-Peng
XP
Li
Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, P.R. China.
Ke-Qiong
KQ
Li
Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, P.R. China.
Wei
W
Xiong
Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, P.R. China.
Jing
J
Li
Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, P.R. China.
Di-Long
DL
Chen
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D005894:Panax / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000073940:Transcription Factor 4; D051996:Transcription Factor RelA / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C530104:CCND1 protein, human; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; C498143:RELA protein, human; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D051996:Transcription Factor RelA; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; C055305:ginsenoside Rh2