Curcumin induces concentration‐dependent alterations in mitochondrial function through ROS in C2C12 mouse myoblasts

Abstract

Curcumin exhibits antioxidant properties in normal cells where the uptake is low, unlike in tumor cells where uptake is high and curcumin increases reactive oxygen species (ROS) production and cell death. Mitochondria are the main source and primary target of cellular ROS. We hypothesized that curcumin would regulate cellular redox status and mitochondrial function, depending on cell sensitivity and/or curcumin concentration in normal cells. We examined the differences between low and high concentrations of curcumin, with specific attention focused on ROS levels, mitochondrial function, and cell viability in mouse C2C12 myoblast under normal and simulated conditions of diabetes.Cells incubated with high concentrations of curcumin (10-50 μM) resulted in decreased cell viability and sustained robust increases in ROS levels. Mechanistic studies showed that increased ROS levels in cells incubated with 20 μM curcumin induced opening of mitochondrial permeability transition pores and subsequent release of cytochrome c, activation of caspases 9 and 3/7, and apoptotic cell death. Low concentrations of curcumin (1-5 μM) did not affect cell viability, but induced a mild increase in ROS levels, which peaked at 2 hr after the treatment. Incubation with 5 μM curcumin also induced ROSdependent increases in mitochondrial mass and membrane potential. Finally, pretreatment with 5 μM curcumin prevented high glucose-induced oxidative cell injury. Our study suggests that mitochondria respond differentially depending on curcumin concentrationdependent induction of ROS. The end result is either cell protection or death. Curcumin may be an effective therapeutic target for diabetes and other mitochondrial diseases when used in low concentrations.

IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice

“…ROS are short-lived molecules, which makes them difficult to be directly measured in vivo. Thus, we and other researchers have used dihydroethidium (DHE) staining to visualize ROS levels in freshly frozen tissue sections 35 , 40 . Figure 7 a shows that the DHE fluorescence intensities were significantly elevated in mouse heart tissues collected on day 3, 4 and 7 after TBI, and returned to similar level as sham-irradiated on day-14.…”

“…ROS level in mouse heart tissues was determined using dihydroethidium staining (DHE, Invitrogen, Waltham, MA) as described previously 35 . Briefly, mouse heart was harvested, snap frozen in a Tissue-Plus OCT compound (Fisher Scientific, Hampton, NH), and cut in 5 µm sections.…”

Fabrication of Curcumin‐Modified TiO2 Nanoarrays via Cyclodextrin Based Polymer Functional Coatings for Osteosarcoma Therapy

“…Although the precise mechanism by which CUR induced apoptosis in tumor cells is unclear, it has been proved that ROS is indeed implicated . It is reported that CUR can induce rapid ROS generation in tumor cells, which leads to cell apoptosis through the activation of mitochondria‐dependent pathways . To confirm this mechanism, here the level of intracellular ROS in MG63 cells treated with CUR‐loaded substrates was detected by staining with dichlorofluorescein diacetate (DCFH‐DA) as an indicator.…”

“…Mitochondria are known to be the best‐characterized sources and primary target of intracellular reactive oxygen species (ROS), which as a group of free radicals can result in damage to DNA, protein or lipids . Although the precise mechanism by which CUR induced apoptosis in tumor cells is unclear, it has been proved that ROS is indeed implicated . It is reported that CUR can induce rapid ROS generation in tumor cells, which leads to cell apoptosis through the activation of mitochondria‐dependent pathways .…”

Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

“…In contrast, a small increase in ROS at low concentrations of curcumin incubation activated signaling pathways to promote mitochondrial health and protect cells from oxidative damage. New or alternative formulations should be developed to manipulate the intracellular concentration of curcumin (Yu, Dohl, Elenberg, Chen, & Deuster, ). In addition, curcumin is a broad spectrum bioactive compound and has been found to be important in several other pathways, including the activation of heat shock proteins (HSPs; Zhou, Beevers, & Huang, ).…”