Ethanol extract from Cnidium monnieri (L.) Cusson induces cell cycle arrest and apoptosis via regulation of the p53‑independent pathway in HepG2 and Hep3B hepatocellular carcinoma cells.

Abstract

Cnidium monnieri (L.) Cusson is a frequently used traditional Chinese medicine that treats gynecological diseases and carbuncles. However, the mechanism of action of C. monnieri remains to be fully elucidated. The present study examined the cell cycle arrest and apoptotic effects resulting from ethanol extract of C. monnieri (CME) in HepG2 (wild‑type p53) and Hep3B (p53‑null) hepatocellular carcinoma cells. An MTT assay was used to confirm the anti‑proliferative effect of CME. The cells were stained with Hoechst 33342 or propidium iodide. It was demonstrated that proliferation of HepG2 cells was suppressed by CME. Cell cycle arrest occurred in the G1 phase following treatment with CME and the number of apoptotic bodies was increased. The expression levels of cell cycle‑associated proteins, including protein kinase B (Akt), glycogen synthase kinase‑3β (GSK‑3β), p53, cyclin E and cyclin‑dependent kinase 2 (CDK2) were determined by western blot analysis. The protein levels of phosphorylated (p)‑Akt, p‑GSK‑3β, p‑MDM2 and cyclin E were decreased, whereas the protein levels of p53, p21 and p‑CDK2 (Thr14/Tyr15) were increased following treatment with CME. Furthermore, treatment or co‑treatment with LY294002 (phosphoinositide‑3‑kinase/Akt inhibitor) or Pifithrin‑α (p53 inhibitor) with CME resulted in CME‑induced G1 arrest which occurred through the p53‑independent signaling pathway in hepatocellular carcinoma cells. In conclusion, CME induces G1 arrest and apoptosis via the Akt/GSK‑3β signaling pathway which is regulated by MDM2‑induced degradation of p21, rather than p53.

• Authors: Eun Gyeong Lim, Guen Tae Kim, Bo Min Kim, Eun Ji Kim, Sang-Yong Kim, Young Min Kim
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 17 Issue 2 Pg. 2572-2580 (Feb 2018) ISSN: 1791-3004 [Electronic] Greece
• PMID: 29207130 (Publication Type: Journal Article)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p21
• Plant Extracts
• Tumor Suppressor Protein p53
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt

Topics

• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Proliferation (drug effects)
• Cnidium (chemistry)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Hep G2 Cells
• Humans
• Liver Neoplasms (metabolism)
• Plant Extracts (pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (metabolism)