Sodium Butyrate Induces Human Colon Carcinoma HT-29 Cell Apoptosis through a Mitochondrial Pathway

2009 ◽  
Vol 37 (3) ◽  
pp. 803-811 ◽  
Author(s):  
L Wang ◽  
H-S Luo ◽  
H Xia
Keyword(s):  
Colon Cancer ◽  
Sodium Butyrate ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Human Colon ◽  
Caspase 9 ◽  
Human Colon Cancer ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ht 29

Some tumours respond favourably to tumour necrosis factor-alpha (TNF-α). Despite this preferential sensitivity, resistance to TNF-α 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-α.

Garcinol exhibits anti-proliferative activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells

2016 ◽  
Vol 36 (7) ◽  
pp. 692-700 ◽  
Author(s):  
T Ranjbarnejad ◽  
M Saidijam ◽  
M sadat tafakh ◽  
M Pourjafar ◽  
F Talebzadeh ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Matrix Metalloproteinase ◽  
Caspase 3 ◽  
Human Colon ◽  
Prostaglandin E ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Prostaglandin E Synthase ◽  
Human Colon Cancer Cells ◽  
Ht 29

Background: Colorectal cancer is the fourth leading cause of death. Various natural compounds are known to have antitumor properties. Garcinol, a polyisoprenylated benzophenone, has antioxidant and anti-inflammatory properties. In the current study, we investigated the anticancer activity of garcinol on human colorectal adenocarcinoma cell line (HT-29) human colon cancer cells. Methods: HT-29 cells were treated with various concentrations of garcinol for 24 h. The effect of garcinol on HT-29 cells proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; the mRNA expression of microsomal prostaglandin E synthase-1 (mPGES-1), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) were examined by quantitative real-time polymerase chain reaction; apoptosis was detected by proportion of sub-G1 cell; caspase 3 activity and prostaglandin E2 (PGE2) level were determined by enzyme-linked immunosorbent assay and HT-29 cells migration was assessed using scratch test. Results: Garcinol preconditioning markedly decreased the expression of mPGES-1, HIF-1α, VEGF, CXCR4, MMP-2, and MMP-9. The proportion of cells in sub-G1 phase and caspase 3 activity were increased by garcinol treatment whereas the cell proliferation, PGE2 level, and cell migration were decreased in these cells, compared to the control group. Conclusion: Our findings suggest that garcinol plays a critical role in elevating apoptosis and inhibiting HT-29 cells proliferation, angiogenesis, and invasion by suppressing the mPGES-1/PGE2/HIF-1α signaling pathways.

Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation

2006 ◽  
Vol 291 (2) ◽  
pp. G288-G296 ◽  
Author(s):  
S. Ramasamy ◽  
S. Singh ◽  
P. Taniere ◽  
M. J. S. Langman ◽  
M. C. Eggo
Keyword(s):  
Ulcerative Colitis ◽  
Colon Cancer ◽  
Cancer Cell Line ◽  
Cell Loss ◽  
Human Colon ◽  
Colon Cancer Cell Line ◽  
Human Colon Cancer ◽  
Histone Deacetylase Inhibition ◽  
Advanced Colon Cancer ◽  
Ht 29

H2S is highly toxic and selectively inhibits butyrate oxidation in colonocytes. Ineffective detoxification may result in mucosal insult, inflammation, and ultimately in colorectal cancer (CRC). Rhodanese can detoxify H2S and is comprised of two isoenzymes: thiosulfate sulfurtransferase (TST) and mercaptopyruvate sulfurtransferase (MST). Using specific antisera to discriminate TST from MST, we found that only TST could detoxify H2S. In sections of normal colon, both enzymes were located on the luminal mucosal surface, and they were expressed in the colonocytes but not in the mucin-secreting goblet cells. Expression of both enzymes was focally lost in ulcerative colitis and markedly reduced in advanced colon cancer, the disease progression correlating with the decreased expression of MST and TST. In HT-29 cells, a human colon cancer cell line, TST activity and expression were significantly increased by butyrate and by histone deacetylase inhibition, agents that promote HT-29 cell differentiation. Sulfide (0.1 mM) also increased TST activity, but higher sulfide concentrations (0.3–3 mM) were toxic. Preincubation in butyrate to increase TST expression, decreased sensitivity of the cells to sulfide toxicity. We conclude that decreased expression of TST (or MST) is a tumor marker for CRC. TST expression is increased in colonocyte differentiation. Dysregulation of TST expression and activity resulting in inability to effectively detoxify could be a factor in the cell loss and inflammation that accompany ulcerative colitis and ultimately then in CRC.

scholarly journals Leptin Counteracts Sodium Butyrate-induced Apoptosis in Human Colon Cancer HT-29 Cells via NF-κB Signaling

2004 ◽  
Vol 279 (16) ◽  
pp. 16495-16502 ◽  
Author(s):  
Patricia Rouet-Benzineb ◽  
Thomas Aparicio ◽  
Sandra Guilmeau ◽  
Cécile Pouzet ◽  
Véronique Descatoire ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Sodium Butyrate ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Induced Apoptosis ◽  
Ht 29
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