Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53.

Abstract

Cisplatin is a chemotherapy drug commonly used for the treatment of human cancers, however, drug resistance poses a major challenge to clinical application of cisplatin in cancer therapy. Recent studies have shown that chrysin, a natural flavonoid widely found in various plants and foods, demonstrated effective anti-cancer activity. In the present study, we found that the combination chrysin and cisplatin significantly enhanced the apoptosis of Hep G2 cancer cells. Combination of chrysin and cisplatin increased the phosphorylation and accumulation of p53 through activating ERK1/2 in Hep G2 cells, which led to the overexpression of the pro-apoptotic proteins Bax and DR5 and the inhibition of the anti-apoptotic protein Bcl-2. In addition, combination of chrysin and cisplatin promoted both extrinsic apoptosis by activating caspase-8 and intrinsic apoptosis by increasing the release of cytochrome c and activating caspase-9 in Hep G2 cells. Our results suggest that combination of chrysin and cisplatin is a promising strategy for chemotherapy of human cancers that are resistant to cisplatin.

• Authors: Xin Li, Jun-Ming Huang, Jian-Ning Wang, Xi-Kun Xiong, Xing-Fen Yang, Fei Zou
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 232 Pg. 12-20 (May 05 2015) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 25770930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier Ireland Ltd.

Chemical References

• BAX protein, human
• Flavonoids
• Proto-Oncogene Proteins c-bcl-2
• Receptors, Tumor Necrosis Factor
• TNFRSF21 protein, human
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• chrysin
• Serine
• Extracellular Signal-Regulated MAP Kinases
• Caspases
• Cisplatin

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Caspases (metabolism)
• Cisplatin (administration & dosage, pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Flavonoids (administration & dosage, pharmacology)
• Gene Expression Regulation (drug effects)
• HCT116 Cells (drug effects, pathology)
• Hep G2 Cells (drug effects, pathology)
• Humans
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Receptors, Tumor Necrosis Factor (metabolism)
• Serine (metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Up-Regulation
• bcl-2-Associated X Protein (metabolism)