RESUMO
An undescribed dammarane triterpenoid saponin Cypaliuruside F was isolated from the leaves of Cyclocarya paliurus in our preliminary study. The MTT assay, flow cytometry, cell scratch, and DAPI staining were used to detect the antitumor effects of Cypaliuruside F on HepG2 cells. Subsequently, network pharmacology and molecular docking analysis were used to analyse the key targets of Cypaliuruside F against HCC. In addition, a Western blot was performed to determine the effects of Cypaliuruside F on the expression of key proteins in HepG2 cells. The experimental results indicated that the damarane triterpenoid saponin Cypaliuruside F from Cyclocarya paliurus inhibits the proliferation of HepG2 cells by inducing apoptosis and cell cycle arrest. These changes may promote the apoptosis of HepG2 cells by inhibiting the expression of mTOR, STAT3, and Bcl-2 while activating Bax.
RESUMO
OBJECTIVE: To investigate the anti-proliferative effects of curcumol, an herbal extract from curcuma, in human hepatocarcinoma HepG2 cells, and its possible molecular mechanism. METHOD: The effects of curcumol on human hepatocarcinoma cells were assessed in vitro. Proliferation of HepG2 cells treated with various concentration (2.5-10 mg x L(-1)) of curcumol was determined using the MTT assay and the distribution of cell cycle of HepG2 cells was analyzed using the FCM technique. Expression of 14 cell cycle regulation-related genes were assessed by TaqMan real-time polymerase chain reaction (RT-PCR) method and Western blot. RESULT: Curcumol significantly inhibited the proliferation of HepG2 cells and induced G1 phase arrest in a dose- and time-dependent manner. The mRNA levels of pRB1, cyclin D1, CDK2, CDK8 and p27KIP1 were elevated, while cyclin A1 decreased, in both of the low (25 mg x L(-1)) and the high dose (100 mg x L(-1)) treatment of curcumol. There were no significant changes in the expression of either cyclin E1 or CDK4. The expression of p53 and its target genes p21WAF1 and Wip1 protein were increased. CONCLUSION: Curcumol can inhibit the proliferation of HepG2 cells in vitro and induce G1 arrest of cell cycle through mechanisms activating p53 and pRB pathways that involve genes of cyclin A1, CDK2, CDK8, p21WAF1 and p27KIP1.
