Sesamol induces mitochondrial apoptosis pathway in HCT116 human colon cancer cells via pro-oxidant effect.
OBJECTIVE
Sesamol lignan is a phenolic compound found in sesame seeds. We investigated the effect of different concentrations of sesamol on oxidative stress in colorectal carcinoma cells (HCT116).


METHODS
Antioxidation in vitro was determined from elimination of the DPPH radical, ferric reducing-antioxidant power (FRAP), O2(-), and peroxyl radical scavenging activity. Intracellular O2(-), H2O2 and GSH levels were determined by DHE, DCFH-DA, and CMF-DA assay, respectively. Cell viability was detected by neutral red assay. Cell cycle proportion and mode of apoptotic HCT116 cells death was analyzed by flow cytometry. Apoptosis in sesamol-treated HCT116 cells was confirmed by morphological changes in the nuclei using DAPI staining and changes in mitochondrial membrane potential using the DiOC6(3) assay.


RESULTS
Sesamol at both low (0.05 and 0.25mM) and high (0.5, 2, 5, and 10mM) concentrations concurrently reduced FRAP reagent and scavenged DPPH, and O2(-). Sesamol at low concentrations scavenged ROO, but ROO-scavenging was decreased at higher concentrations. Sesamol suppressed cell viability via disruption of cell cycle progression at high concentrations (0.5, 1, 2, and 5mM), thereby causing S-phase arrest and inducing apoptosis-through the production of intracellular O2(-), mitochondrial dysfunction, and DNA fragmentation.


CONCLUSIONS
High concentrations of sesamol induced the mitochondrial apoptosis pathway in human colon cancer HCT116 cells via a pro-oxidant effect.
Graduate School, Biomedical Science Program, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: M.Khamphio@gmail.com.
Munthipha
M
Khamphio
Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: sahapat@kku.ac.th.
Sahapat
S
Barusrux
Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: natthida@kku.ac.th.
Natthida
N
Weerapreeyakul
D017209:Apoptosis / Q000187:drug effects*; D052117:Benzodioxoles / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D045325:HCT116 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000494:pharmacology*
D052117:Benzodioxoles; D010636:Phenols; D017382:Reactive Oxygen Species; C025583:sesamol
Apoptosis; Chemopreventive effect; Human colon cell line; Reactive oxygen species; Sesame; Sesamol