Title:The Combination of Chrysin and Cisplatin Induces Apoptosis in HepG2 through
Down-regulation of cFLIP and Activity of Caspase
Volume: 23
Issue: 4
Author(s): Yang-Xin Luo, Bao-Ying Peng, Zheng-Hao Chen, Xi-Kun Xiong, Jun-Ming Huang, Mei-Fen Chen, Feng-Yan Wang, Xin Li*Jian-Ning Wang*
Affiliation:
- Guangdong
Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Dashi, Panyu District, Guangzhou, Guangdong Province,
P.R. China, 511430
- Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University,
Guangdong Provincial Key Laboratory of Stomatology, 56, Ling Yuan Xi Road, Guangzhou, Guangdong Province, P.R. China,
510055
Keywords:
Chrysin, cisplatin, apoptosis, cFLIP, caspase , HepG2.
Abstract:
Abstract: Aim: The study aims to investigate the combined effects of chrysin and cisplatin on hepatoma(HepG2) cell
lines in vivo and in vitro.
Objective: Studies have suggested that chrysin can enhance the sensitivity of tumor cells to apoptosis. Drug resistance
in tumor cells reduced the effectiveness of chemotherapy drugs such as cisplatin. We investigated whether the combination
of chrysin and cisplatin can induce more apoptosis than chrysin alone and cisplatin alone.
Methods: HepG2 cells were pretreated with chrysin for 2 h, followed by the addition of cisplatin for another 24 h. The
morphologic changes were observed under inverted microscope and the cell viability was measured using the MTT
test. The protein and cleavage of caspase-3,8,9, PARP, and cFLIP were determined by Western blotting.
Results: The cell viability of the HepG2 cell can be reduced by the combination of chrysin pretreatment for 2 h and
cisplatin addition for 24 h; Caspase-3,8,9 and PARP were cleaved after 12 h treatment with chrysin and cisplatin; Pancaspase
inhibitor, Z-VAD-fmk, could reverse the apoptosis induced by chrysin and cisplatin in HepG2 cells; cFLIP
was down-regulated by the combination of chrysin and cisplatin, and could be reversed by Z-VAD-fmk; the xenografted
HepG2 cells formed a tumor in one week; At the end of the experiment, there were significant differences in relative
tumor volume (RTV) and relative tumor proliferation rate between the combined group and the control group, the
chrysin group and the cisplatin group; Western blotting showed that the levels of PARP, cFLIP, and caspase-3 proteins
in isolated tumor tissues also decreased under the combined action of chrysin and cisplatin.
Conclusion: The combination of chrysin and cisplatin induces apoptosis of hepatic tumor in vivo and in vitro. It downregulates
cFLIP and then activates caspase-8, which triggers caspase-mediated apoptosis of HepG2 cell.
