Sodium butyrate promotes apoptosis in breast cancer cells through reactive oxygen species (ROS) formation and mitochondrial impairment

Abstract

BackgroundSodium butyrate (NaBu) is a short-chain fatty acid which serves as a histon deacetylase inhibitor and has received considerable interest as a possible regulator of cancer cell death. The regulatory effect of NaBu on cancer cell growth or death has yet to be illustrated in many cancers including breast cancer. This study is aimed to elucidate the possible effect of NaBu on regulation of breast cancer growth and apoptosis.MethodsThe cytotoxic effect of NaBu on the growth of breast cancer cells (MCF-7 and MDA-MB-468) and normal breast cells (MCF-10A) was determined using MTT assay. Annexin-V-FITC staining and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry, the level of mitochondrial membrane potential (Δψm), Reactive oxygen species (ROS)formation and caspase activity were determined accordingly.ResultsBased on our data, NaBu induced a dose and time-dependent cell toxicity in breast cancer cells which was related to the cell cycle arrest and induction of apoptosis. The impact of NaBu on MCF-10A cell toxicity, cell cycle distribution and apoptosis was inconsiderable. NaBu-elicited apoptosis was accompanied by the elevated level of ROS, increased caspase activity and reduced mitochondrial membrane potential (Δψm) in MCF-7 and MDA-MB-468 cells and with no effect on the above mentioned factors in MCF-10A cells.ConclusionsOur study provided insight in to the role of NaBu on the regulation of breast cancer cell growth and lighten up the pro-apoptotic activity of NaBu.

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“…Inhibition of HDACs by butyrate has been shown to sensitise cancer cells to ROS induced apoptosis [39]. In vitro administration of exogenous butyrate suppresses proliferation of BrCa cells through senescence and induces apoptosis [40]. Whilst our transcriptomic data did not reveal any differences in transcription of cell cycle regulatory genes, we do observe decreased expression of pro-apoptotic genes such as BNIP3 and increased pro-survival genes such as HERPUD1 and URI which is consistent with butyrate's bioactivity.…”

Sodium butyrate inhibits migration and induces AMPK‐mTOR pathway‐dependent autophagy and ROS‐mediated apoptosis via the miR‐139‐5p/Bmi‐1 axis in human bladder cancer cells

“…Sodium butyrate is widely known as an Histone deacetylases (HDAC) inhibitor . HDACs, which target lysine residues, are epigenetic determinants that are essential for transcriptional regulation via promoting chromatin condensation .…”

“…Sodium butyrate is widely known as an Histone deacetylases (HDAC) inhibitor. 11 HDACs, which target lysine residues, are epigenetic determinants that are essential for transcriptional regulation via promoting chromatin condensation. 50,51 Tsung-Hua Hsieh and colleagues reported that acetylating RUNX3 enhanced the binding of the RUNX3/ p300 complex to the miR-125a-5p promoter and that silencing RUNX3 had the same biological effect as decreasing miR-125a-5p in human breast cancer cells.…”

“…Reactive oxygen species serve as important mediators in various biological processes and stimuli that regulate cell survival or death, such as chemotherapeutic agents, starvation, and radiation. 11,24,25,41 Although moderate levels of ROS stimulate cell proliferation, overloaded ROS, on the contrary, leads to cell apoptosis and autophagy via various pathways. 24,26,27,38,53,54 In this study, diminished MMP (a marker of mitochondrial function) was detected ( Figure 3A).…”

“…Some researchers have reported that sodium butyrate might cause mitochondrial damage and exert antitumor effects. 10,11 Therefore, we investigated the mitochondrial membrane potential (MMP), which is another hallmark of mitochondrial function and apoptosis, using JC-1. 44 Figure 3A shows that NaB treatment resulted in a marked decrease in MMP.…”