Cell Cycle Arrest Effects by Artemisia annua Linné in Hep3B Liver Cancer Cell

Abstract

Cells proliferate via repeating process that growth and division. This process is G1, S, G2 and M four phases consists. Monitoring the progression of the cell cycle is a specific step that to be a continuous process is repeated to adjust the start of the next step. At this time, this process is called a Checkpoint. Currently, there are three known checkpoints that G1-S phase, G2-M phase, and the M phase. In this study, we confirmed that cell cycle arrest effects by ethanol extracts of Artemisia annua Linne (AAE) in Hep3B liver cancer cells. AAE was regulated proteins which involved in cell cycle such as pAkt, pMDM2, p53, p21, pCDK2 (T14/Y15). AAE induced cell cycle arrest in G1 checkpoint through phosphorylation of CDK2. Akt and p53 upstream is inhibited by AAE and p53 activated by non-activated pMDM2, p53 inhibitor. Thereby, activated p53 is transcript to p21 and activated p21 protein is combined with Cyclin E-pCDK2 complex. Therefore, we confirmed that AAE-induced cell cycle arrest was occurred by p21-Cyclin E-pCDK2 complex by inhibition of pAkt signal. Because of this cell cycle can't pass to S phase from G1 phase.

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

“…According to a previous study, GSK-3β phosphorylates MDM2 protein and overexpression of MDM2 promotes degradation of p21 through proteasome-mediated degradation in a p53-independent manner (30,31). Also, many of the studies have reported that natural extracts induce apoptosis and cell cycle arrest through controlling the p53-independent signaling pathway (32)(33)(34). Moreover, overexpression of p21 induces the expression of pro-apoptotic protein Bax and modulates the Bcl-2:Bax ratio in Hep3B cells (35).…”