Matrine inhibits proliferation and induces apoptosis via BID-mediated mitochondrial pathway in esophageal cancer cells.

Abstract

Matrine, as a member of Sophora family, is an alkaloid found in plants, and produces plethora pharmacological effects, including anti-cancer effects. However, the mechanism involved remains largely unknown. This study is conducted to investigate the anti-cancer mechanisms of matrine in human esophageal cancer in vitro and in vivo. In human esophageal cancer cell Eca-109, matrine significantly decreased the cell viability in a dose-dependent manner, and induced apoptosis as well as cell cycle arrest in G0/G1 phase by up-regulation of P53 and P21. The expression of several apoptosis-related proteins in cells and tumor tissues were evaluated by Western blot analysis. We found that matrine induced cell apoptosis by down-regulation of the ratio of BCL-2/BID and increasing activation of caspase-9. Further studies indicated that matrine induced apoptosis of Eca-109 was through the mitochondria-mediated internal pathway, but not by death receptor-mediated extrinsic apoptotic pathway, which was confirmed by the fact that Bid translocated from the nucleus to mitochondria during the process of the apoptosis induced by matrine. In vivo study found that matrine effectively inhibited the tumor formation of Eca-109 cells in nude mice. Our study suggests that matrine could serve as a potential novel agent from natural products to treat esophageal cancer.

• Authors: Qiao Wang, Haoxin Du, Guojun Geng, Huan Zhou, Minying Xu, Hanwei Cao, Bing Zhang, Gang Song, Tianhui Hu
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 41 Issue 5 Pg. 3009-20 (May 2014) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 24510386 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Antineoplastic Agents
• BH3 Interacting Domain Death Agonist Protein
• Proto-Oncogene Proteins c-bcl-2
• Quinolizines
• Cytochromes c
• Poly(ADP-ribose) Polymerases
• Caspase 8
• Caspase 9
• Matrines

Topics

• Alkaloids (administration & dosage, pharmacology)
• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• BH3 Interacting Domain Death Agonist Protein (metabolism)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cytochromes c (metabolism)
• Disease Models, Animal
• Esophageal Neoplasms (metabolism, pathology)
• Humans
• Male
• Mice
• Mitochondria (metabolism)
• Models, Biological
• Poly(ADP-ribose) Polymerases (metabolism)
• Protein Transport
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Quinolizines (administration & dosage, pharmacology)
• Signal Transduction (drug effects)
• Tumor Burden
• Xenograft Model Antitumor Assays
• Matrines