Butyrate cells, effect

MENZEL T, SCHAUBER J, KRETH F, KUDLICH T, MELCHER R, GOSTNER A, SCHEPPACH W, LUHRS H (2002) Butyrate and aspirin in combination have an enhanced effect on apoptosis in human colorectal cancer cells. Eur J Cancer Prev. 11 271-81. 

Novogrodsky A, Dvir A, Ravid A, Shkolnik T, Stenzel KH, Rubin AL, Zaizov R. (1983) Effect of polar organic compounds on leukemic cells. Butyrate-induced partial remission of acute myelogenous leukemia in a child. Cancer 51 9-14. 

Crew TE, Elder DJE, Paraskeva C A. Cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug enhances the growth inhibitory effect of butyrate in colorectal carcinoma cells expressing COX-2 protein regulation of COX-2 by butyrate. Carcinogenesis 2000 21 69-77. 

Hossain, Z., Konishi, M., Hosokawa, M., and Takahashi, K. (2006). Effect of polyunsaturated fatty acid-enriched phosphatidylcholine and phosphatidylserine on butyrate-induced growth inhibition, differentiation and apoptosis in Caco-2 cells. Cell Biochem. Fund. 24, 159-165. 

This study describes the effect of sodium butyrate on glyco-lipids from four human colonic tumor cell lines, SKCO-1, HT-29, SW-480 and SW-620 and a human fetal intestinal line, FHS. 

Effect of Sodium Butyrate on Morphology and Cell Growth. FHS, SKCO-1, HT-29 did not show any significant morphological changes with sodium butyrate. SW-480 and SW-620 cells produce angular cells rich in cellular membranes. These processes were pronounced with SW-620 cell lines. 

In the present study, sodium butyrate had a differentiated effect on cell morphology. Sodium butyrate caused the SW-620 lines to become markedly angular with extension of many membraneous processes. These effects were also seen with the SW-480 cell lines but were less pronounced. No morphological changes were observed when SKCO-1, HT-29 and FHS cell lines were cultured in sodium butyrate. 

The concentration of sodium butyrate was observed to have a differential effect on cell growth in colonic cell lines. After culturing for 8 days with 5 mM sodium butyrate, the cell protein per flask of the SCKO-1 line was decreased to less than 10% of the control cultures. In the SW-620 culture,cell protein per... 

Figure 2. Effect of butyrate treatment on GM3 content of HeLa cells...

Exposure of HeLa cells to butyrate had no effect on the activity of GM3-sialidase when GM3 specifically labeled in the sialic acid residue was used as substrate (Fig. 3a). We were unable to detect any "ecto"-sialidase activity in either control or butyrate-treated cells (14) although others have postulated that such an enzyme is important in regulating plasma membrane gangliosides (15,16). In contrast, the activity of the specific sialyl transferase involved in GM3 biosynthesis increased over 20-fold following butyrate treatment (Fig. 3b). The effect was specific as activities of the other glycosphingolipid transferases that could be measured in HeLa cells were not altered in butyrate-treated cells (4,8,17). 

Increased sialyl transferase activity was dose and time dependent, and reversible (8). Maximal activity was obtained by exposing the cells to 5 mM butyrate for 24 h. Following removal of butyrate, the enzyme had a half-life of 7 h and activity reached control levels by 24 h. Of the numerous short chain fatty acids and derivatives tested, only butyrate, pentanoate and propionate were effective (8). 

In recent work on CHO cells, it had been suggested that the effects of butyrate are mediated by cyclic AMP (18). We found, however, that cyclic AMP (2 mM), its mono- (1 mM and dibutyryl (0.5 mM) derivatives, theophylline and prostaglandins did not cause an elevation in si alyl transferase activity (1). Choleragen, which is a potent and persistant activator of adenylate cyclase (see below), also did not elevate sialyl transferase activity in HeLa cells (Table I) or alter cell morphology (unpublished observations). Thus, it is unlikely that these effects of butyrate are mediated by elevation of cyclic AMP levels. 

Increased GM3 content was also observed in another strain of HeLa exposed to butyrate but not in butyrate-treated normal human fibroblasts (experiments in collaboration with E. Stanbridge, University of California at Irvine and R. 0. Brady, NINCDS). Butyrate appeared to have similar effects on GM3 biosynthesis in KB cells, another human carcinoma-derived cell line (20). Butyrate-treated KB cells had 9-fold elevated levels of sialyl transferase activity. In contrast, butyrate as well as dibutyryl-... 

Figure 5. Effect of labeled and unlabeled choleragen concentrations on n5I-choleragen binding to control and butyrate-treated HeLa cells...

If GM1 is the choleragen receptor, then butyrate-treated cells should have an increase in GM1 content. This is demonstrated in Table IV. Although GM1 could not be detected in control HeLa cells, they would contain less than 1 pmol per mg protein based on the limits of the sensitivity of the analytical procedure (5). GM1 was quantitated in the butyrate-treated cells (28.5 pmol per mg protein) and this increase is similar to the 32-fold increase in toxin binding observed in cells from the same experiment. The delipidated residue contained less than 1% of the toxin binding found in intact cells (Table IV). In addition, removal of the cells from the culture dishes with trypsin as opposed to the mechanical scraping routinely used had no effect on 125I-cholera-gen binding to either control or butyrate-treated cells (5). 

Table IV. Effect of Sodium Butyrate on Choleragen Receptors and GM1 Content of HeLa Cells...

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