The apoptosis of HepG2 cells and effect of C-jun N-terminal kinase signaling pathway induced by luteolin combined with cisplatin
10.3760/cma.j.issn.1006-9801.2014.03.002
- VernacularTitle:木犀草素联合顺铂诱导人类肝癌HepG2细胞凋亡及对C-jun氨基末端激酶信号通路的影响
- Author:
Shanling XU
;
Guanze XIONG
- Publication Type:Journal Article
- Keywords:
Liver neoplasms;
Luteolin;
Cisplatin;
Apoptosis;
C-jun N-terminal kinase
- From:
Cancer Research and Clinic
2014;26(3):148-152
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the increased cytotoxicity induced by luteolin and cisplatin cotreatment and validate its mechanism.Methods HepG2 cells were pretreated with luteolin for 1 hour or remained untreated and followed by exposure to cisplatin.Cells were stained with Hoechst,and Caspase-3 activity was detected by spectrophotometry.Cell death was detected by LDH release assay.Phosphated C-jun N-terminal kinase (JNK) and total JNK1 were detected by Western blot.Results Luteolin significantly enhanced Caspase-3 activity and HepG2 cells apoptosis by cisplatin.The cell death rates by co-treatment with different concentration of luteolin (0-20 μmol/L) and cisplatin (10 μg/ml) were much higher than cisplatin or luteolin alone treatment.Combined treatment of luteolin (20 μmol/L) with cisplatin (10 μg/ml) killed 47.66 ％ of HepG2 cells.There were significant differences on cell death between combination group and single reagent group (F =535.48,P ＜ 0.01).Combination group showed better efficacy than single reagent group.The Caspase-3 activity of HepG2 cells treated by luteolin (20 μmol/L),cisplatin (10 μg/ml) or luteolin (20 μmol/L)plus cisplatin (10 μg/ml) were 1.94,1.74 and 8.12 times of negative control group respectively.Combination treatment induced sustained activation of JNK signaling pathway.Conclusions Enhancing cisplatin-induced JNK activation by luteolin leads to increased cytotoxicity in HepG2 cells.The combination of luteolin and cisplatin is an effect apporch for improving the anticancer value of cisplatin,which has implications in cancer prevention and therapy.
