Dyah Paramita, J.D.P. Wisnubroto
Background: Methylglyoxal (MG) is an extremely reactive α-ketoaldehyde endogenously produced by various metabolic pathways, including the dephosphorylation of glycolytic intermediates, metabolites of the polyol pathway, and aminoacetone metabolism. MG cytotoxicity occurs through the induction of apoptosis. There are multiple mechanisms by which MG can induce apoptosis, e.g., through the generation of reactive oxygen species (ROS), induction of oxidative DNA damage, or accumulation of a specific MG-derived advanced glycation end product (AGE). Objective: This study aimed to investigate the effect of MG on ROS production, KI-67 expression, and caspase-3 expression in MCF-7 cells. Methods: At confluency, MCF-7 cells were divided into five groups, including control (untreated); and MCF-7 cells exposed to MG (1 mM) for 0; 12; 24; and 48 h of incubation. Reactive oxygen species level, KI-67 expression, and caspase-3 expression were evaluated by laser scanning confocal microscopy. Results: The level of reactive oxygen species was significantly lower in 12 h of incubation compared to the control group (p <.05). The reactive oxygen species level was significantly higher in 48 h of incubation compared to the control group (p <.05). The expressions of KI-67 was significantly higher in all groups of MCF-7 cells treated with MG compared to the control group (p <.05). The maximal expression of KI-67 was achieved in 12 h of incubation. The expression of KI-67 was significantly lower in 48 h of incubation compared to 12 h of incubation (p <.05). The caspase-3 expressions were significantly greater in all groups of MCF-7 cells treated with MG groups compared to the control group (p <.05). The maximal expression of caspase-3 was achieved in 48 h of incubation. The increased expression of caspase-3 in 48 h of incubation was significantly higher compared to 0; 12; and 24 h of incubation (p <.05). Conclusion: Methylglyoxal at 48 h of incubation disturbs the defense mechanisms of MCF-7 cells to reactive oxygen species. This incubation time also induces apoptosis and inhibits the cells proliferation. Therefore, this may provide a novel approach for inhibiting the breast cancer cell growth. © 2018 Elsevier Inc.
Department of Surgery, Saiful Anwar General Hospital, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia; Division of Surgical Oncology, Department of Surgery, Saiful Anwar General Hospital, Brawijaya University, Malang, East Java, Indonesia
