Sodium butyrate induces human colon carcinoma HT-29 cell apoptosis through a mitochondrial pathway
1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.
Abstract:
Some tumours respond favourably to tumour necrosis factor-alpha (TNF-alpha). Despite this preferential sensitivity, resistance to TNF-alpha remains a clinical problem and more interest is now being focused on finding compounds that induce apoptosis through other pathways. Sodium butyrate (NaBt) has anti-tumour effects on colon cancer cells, inhibiting cell growth and promoting differentiation and apoptosis. In this study we investigated whether NaBt induced apoptosis in the human colon cancer cell line HT-29 and examined the intracellular mechanisms involved. Pre-incubation of cells with NaBt significantly increased apoptosis as measured by fluorescence activated cell sorter analysis and mitochondrial membrane potential determination. This effect could be blocked with the caspase inhibitors, z-VAD-fmk (pan-caspase inhibitor), z-DEVD-fmk (caspase-3 inhibitor) and z-LEHD-fmk (caspase-9 inhibitor), but not with z-IETD-fmk (caspase-8 inhibitor). Enhancement of caspase-3 and caspase-9 activities suggests that NaBt induces apoptosis via mitochondrial pathways not involving TNF-alpha.
Insights
Sodium butyrate (NaBt) effectively triggers apoptosis in human colon cancer cells. This process involves mitochondrial pathways and enhances caspase-3 and caspase-9 activity, offering a new therapeutic avenue beyond tumor necrosis factor-alpha (TNF-alpha).
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Tumor necrosis factor-alpha (TNF-alpha) shows promise in cancer treatment, but resistance limits its efficacy.
- Alternative pathways for inducing apoptosis are crucial for overcoming treatment resistance.
- Sodium butyrate (NaBt) exhibits anti-cancer properties, including growth inhibition, differentiation, and apoptosis induction in colon cancer.
Purpose of the Study:
- To investigate the induction of apoptosis by Sodium butyrate (NaBt) in the human colon cancer cell line HT-29.
- To elucidate the intracellular mechanisms underlying NaBt-induced apoptosis.
Main Methods:
- Human colon cancer cell line HT-29 was treated with Sodium butyrate (NaBt).
- Apoptosis was assessed using fluorescence activated cell sorter (FACS) analysis and mitochondrial membrane potential determination.
- The role of caspases was evaluated using specific caspase inhibitors (z-VAD-fmk, z-DEVD-fmk, z-LEHD-fmk, z-IETD-fmk).
Main Results:
- Sodium butyrate (NaBt) significantly increased apoptosis in HT-29 cells.
- NaBt-induced apoptosis was inhibited by pan-caspase, caspase-3, and caspase-9 inhibitors, but not by a caspase-8 inhibitor.
- Enhanced activity of caspase-3 and caspase-9 was observed following NaBt treatment.
Conclusions:
- Sodium butyrate (NaBt) effectively induces apoptosis in human colon cancer cells.
- The mechanism involves the mitochondrial pathway and activation of caspase-3 and caspase-9.
- NaBt represents a potential therapeutic agent for colon cancer, acting independently of the TNF-alpha pathway.
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