Synergistic inhibitory effect of berberine and d-limonene on human gastric carcinoma cell line MGC803.

Abstract

This study aims at evaluating the anticancer effects of berberine hydrochloride (berberine) and d-limonene, alone and in combination, on human gastric carcinoma cell line MGC803 to determine whether berberine and d-limonene work synergistically and elucidate their mechanisms. MGC803 cells were treated with berberine and d-limonene, alone and in combination, for 24-48 h. The inhibitory effects of these drugs on growth were determined by MTT assay. The combination index and drug reduction index were calculated with the Chou-Talalay method based on the median-effect principle. Flow cytometry and laser scanning confocal microscopy were employed to evaluate the effects of both drugs on cell-cycle perturbation and apoptosis, generation of reactive oxygen species (ROS), mitochondrial membrane potential, and expression of Bcl-2 and caspase-3 in MGC803 cells. Berberine or d-limonene alone can inhibit the growth of MGC803 cells in a dose- and time-dependent manner. Berberine and d-limonene at a combination ratio of 1:4 exhibited a synergistic effect on anti-MGC803 cells. The two drugs distinctly induced intracellular ROS generation, reduced the mitochondrial transmembrane potential (ΔΨm), enhanced the expression of caspase-3, and decreased the expression of Bcl-2. The combination of berberine and d-limonene showed more remarkable effects compared with drugs used singly in MGC803 cells. The combination of berberine and d-limonene exerted synergistic anticancer effects on MGC803 cells by cell-cycle arrest, ROS production, and apoptosis induction through the mitochondria-mediated intrinsic pathway.

• Authors: Xiu-Zhen Zhang, Ling Wang, Dong-Wu Liu, Guang-Yan Tang, Hong-Yu Zhang
• Journal: Journal of medicinal food (J Med Food) Vol. 17 Issue 9 Pg. 955-62 (Sep 2014) ISSN: 1557-7600 [Electronic] United States
• PMID: 25045784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Cyclohexenes
• Plant Extracts
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Terpenes
• Berberine
• Limonene
• Caspase 3

Topics

• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Berberine (pharmacology, therapeutic use)
• Caspase 3 (metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Coptis (chemistry)
• Cyclohexenes (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Synergism
• Evodia (chemistry)
• Humans
• Limonene
• Membrane Potential, Mitochondrial (drug effects)
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Reactive Oxygen Species (metabolism)
• Stomach Neoplasms (drug therapy, metabolism)
• Terpenes (pharmacology, therapeutic use)