Molecular mechanism of cardol, isolated from Trigona incisa stingless bee propolis, induced apoptosis in the SW620 human colorectal cancer cell line.

Abstract

BACKGROUND:

Cardol is a major bioactive constituent in the Trigona incisa propolis from Indonesia, with a strong in vitro antiproliferative activity against the SW620 colorectal adenocarcinoma cell line (IC50 of 4.51 ± 0.76 μg/mL). Cardol induced G0/G1 cell cycle arrest and apoptotic cell death. The present study was designed to reveal the mechanism of cardol's antiproliferative effect and induction of apoptosis.

METHODS:

Changes in cell morphology were observed by light microscopy. To determine whether the mitochondrial apoptotic pathway was involved in cell death, caspase-3 and caspase-9 activities, western blot analysis, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were assayed.

RESULTS:

Changes in the cell morphology and the significantly increased caspase-3 and caspase-9 activities, plus the cleavage of pro-caspase-3, pro-caspase-9 and PARP, supported that cardol caused apoptosis in SW620 cells within 2 h after treatment by cardol. In addition, cardol decreased the mitochondrial membrane potential while increasing the intracellular ROS levels in a time- and dose-dependent manner. Antioxidant treatment supported that the cardol-induced cell death was dependent on ROS production.

CONCLUSION:

Cardol induced cell death in SW620 cells was mediated by oxidative stress elevation and the mitochondrial apoptotic pathway, and these could be the potential molecular mechanism for the antiproliferative effect of cardol.

• Authors: Paula Mariana Kustiawan, Kriengsak Lirdprapamongkol, Tanapat Palaga, Songchan Puthong, Preecha Phuwapraisirisan, Jisnuson Svasti, Chanpen Chanchao
• Journal: BMC pharmacology & toxicology (BMC Pharmacol Toxicol) Vol. 18 Issue 1 Pg. 32 (05 04 2017) ISSN: 2050-6511 [Electronic] England
• PMID: 28472978 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Reactive Oxygen Species
• Resorcinols
• Propolis
• Caspase 3
• Caspase 9
• adipostatin A

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Bees (chemistry)
• Caspase 3 (genetics, metabolism)
• Caspase 9 (genetics, metabolism)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Shape (drug effects)
• Drug Screening Assays, Antitumor
• Gene Expression (drug effects)
• Humans
• Indonesia
• Membrane Potential, Mitochondrial (drug effects)
• Propolis (chemistry)
• Reactive Oxygen Species (metabolism)
• Resorcinols (pharmacology)