Luteolin induces mitochondrial apoptosis in HT29 cells by inhibiting the Nrf2/ARE signaling pathway

Abstract

The aim of the current study was to investigate luteolin-induced apoptosis and the molecular mechanisms underlying it in HT29 cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess the cytotoxicity of luteolin on HT29 cells, and a dichloro-dihydro-fluorescein diacetate assay was used to measure cellular levels of reactive oxygen species (ROS). The effects of luteolin on the mitochondrial membrane potential were also evaluated. Bax and Bcl-2 mRNA expression were determined using reverse transcription-quantitative PCR. Additionally, western blot analysis was performed to assess changes in cytochrome c and caspase-3 protein expression. Localization of nuclear factor erythroid 2-related factor 2 (Nrf2) in the nucleus was also assessed using immunofluorescence. Luteolin exhibited cytotoxicity on HT29 cells in a time-and concentration-dependent manner. Additionally, ROS production was indicated to be increased and ROS scavenging was decreased, which resulted in a significant increase in the levels of ROS in the cells. The mitochondrial membrane potential was indicated to decrease following luteolin treatment. At the molecular level, luteolin significantly increased the mRNA expression of Bax and the protein expression of cytochrome c, caspase-3, p47 phox and p22 phox . The results revealed that luteolin decreased Bcl-2 protein expression and inhibited the nuclear localization of Nrf2. In conclusion, the current study indicated that luteolin inhibited HT29 cell proliferation and induced apoptosis via the mitochondrial pathway.

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“…Among these proteins, the changes in mitochondrial membrane permeability are determined by the relative levels of Bcl-2 and Bax. Briefly, during the mitochondrial apoptotic pathway, the mitochondrial membrane is damaged as a result of the apoptotic effect promoted by Bax, whereas Bcl-2 inhibits apoptosis by maintaining the integrity of the mitochondrial membrane [54]. Thus, the differences between the changes of the mitochondrial potential of cells treated with seed coat extracts and those treated with peel and seed extracts could also be related to the presence of salidroside, hydroxysalidrose, sakuranetin and luteolin.…”

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“…Chian et al reported that luteolin is a strong inhibitor of Nrf2 in vitro. They further confirmed that luteolin inhibited the Nrf2 signaling pathway and lung tumor growth in vivo by using an Nrf2 −/− mouse model [41][42][43][44]. The effects of luteolin on the Nrf2 pathway may be cell-type specific and involve multiple signaling pathways and mechanisms.…”

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