Regulation of human colonic cell line proliferation and phenotype by sodium butyrate

Basson, Marc D.; Turowski, G; Rashid, Zaihan; Fu, Hong; Madri, Joseph A.

doi:10.1007/bf02093601

Cited by 56 publications

(35 citation statements)

References 46 publications

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“…APC is able to increase MDA-MB-231 cell migration over Na butyrate treatment alone by the same ratio as APC treatment compared to control. Further, the pathways activated by Na butyrate [52,53] are not the same pathways utilized by APC to increase migration in these cells. Other pathways, such as MAPK and PI3K pathways [26], that have been implicated in the mechanism by which APC increase HUVEC proliferation may have a role in increasing migration in the MDA-MB-231 cells.…”

Section: Discussionmentioning

confidence: 90%

“…Na butyrate inhibits histone deacetylase, increases p21 expression, and decreases cyclin D gene expression [50] resulting in an arrest of the cell in G2 [51]. Na butyrate also induces cell differentiation [50], as shown with an increase in lipid accumulation, and a reduction in migration across multiple extracellular matrices [52]. We found that unlike the effects of APC on HUVEC proliferation, in breast cancer cells, binding to EPCR and activation of PAR-1 by APC increase migration but not proliferation.…”

Section: Discussionmentioning

confidence: 99%

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Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Beaulieu

Church

2007

Experimental Cell Research

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Activated protein C (APC) is a serine protease that regulates thrombin (IIa) production through inactivation of blood coagulation factors Va and VIIIa. APC also has non-hemostatic functions related to inflammation, proliferation, and apoptosis through various mechanisms. Using two breast cancer cell lines, MDA-MB-231 and MDA-MB-435, we investigated the role of APC in cell chemotaxis and invasion. Treatment of cells with increasing APC concentrations (1-50 μg/ml) increased invasion and chemotaxis in a concentration-dependent manner. Only the active form of APC increased invasion and chemotaxis of the MDA-MB-231 cells when compared to 3 inactive APC derivatives. Using a modified "checkerboard" analysis, APC was shown to only affect migration when plated with the cells; therefore, APC is not a chemoattractant. Blocking antibodies to endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1) attenuated the effects of APC on chemotaxis in the MDA-MB-231 cells. Finally, treatment of the MDA-MB-231 cells with the proliferation inhibitor, Na butyrate, showed that APC did not increase migration by increasing cell number. Therefore, APC increases invasion and chemotaxis of cells by binding to the cell surface and activating specific signaling pathways through EPCR and PAR-1.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Beaulieu

Church

2007

Experimental Cell Research

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“…IAP is a well-established marker of di erentiation in HT29 cells and other colon cancer cell lines (Choi et al, 1990;Hodin et al, 1996, Schroy et al, 1994Goldberg et al, 1996;Navarro et al, 1997;Basson et al, 1996). IAP activity was examined using a histochemical demonstration kit for alkaline phosphatase detection (Sigma) (Goldberg et al, 1996) and also by Western blot analysis using a rabbit polyclonal antibody that recognizes human intestinal alkaline phosphatase (Dako), as described previously (Goldberg et al, 1996).…”

Section: E Ect Of P27 Kip1 Overexpression On Cell DI Erentiationmentioning

confidence: 99%

“…Sodium butyrate (SB) was used for induction of di erentiation. This short chain fatty acid is a di erentiating agent for various cell types (Navarro et al, 1997;Siavoshian et al, 1997;Basson et al, 1996;Conway et al, 1995;Swarovsky et al, 1994). By histochemical analyses IAP positive cells were only rarely detected in the untreated vector control and the overexpressor derivatives.…”

Section: E Ect Of P27 Kip1 Overexpression On Cell DI Erentiationmentioning

confidence: 99%

Comparative effects of overexpression of p27Kip1 and p21Cip1/Waf1 on growth and differentiation in human colon carcinoma cells

et al. 1999

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Recent studies have shown that decreased expression of p27 Kip1 is associated with high grade tumors and an unfavorable prognosis in several types of human cancer. To clarify the role of p27 Kip1 in colon cancer, we have overexpressed this protein in the HT29 colon cancer cell line. The derivatives displayed an increase in the p27 Kip1 protein in cyclin E/CDK2 immunoprecipitates and a decrease in cyclin E-associated kinase activity when compared to vector control clones, providing evidence that the overexpressed protein was functional. Clones with a high level of p27 Kip1 displayed partial growth inhibition in monolayer culture and a decrease in plating e ciency, even though they expressed increased levels of the cyclin D1 protein. Using alkaline phosphatase expression as a marker, we found that the p27 Kip1 overexpressor clones displayed a 2 ± 3-fold increase in sensitivity to induction of di erentiation by 2 mM sodium butyrate. In contrast to these results, derivatives of HT29 cells that stably overexpressed p21 Cip1/Waf1 displayed decreased sensitivity to the induction of di erentiation. These ®ndings may explain why decreased levels of p27 Kip1 in certain human cancers is associated with high grade (poorly di erentiated) tumors, and suggest that strategies that increase the level of p27 Kip1 may be useful in cancer therapy.

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“…SCFAs are well known to promote differentiation in transformed erythroid and colonic epithelial cell lines, [26][27][28][29] but their effects on erythroid differentiation in primary cells had not been described. Normal erythroid differentiation in murine development parallels advancing fetal age.…”

Section: Introductionmentioning

confidence: 99%

Short-chain fatty acid–mediated effects on erythropoiesis in primary definitive erythroid cells

Bhatia

Hallock

Dutta

et al. 2009

Blood

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IntroductionThe human ␤-and ␣-globin gene loci are developmentally regulated and are arrayed spatially in the order in which they are expressed developmentally, respectively, 5Ј-⑀-G ␥-A ␥-␤-3Ј and 5Ј--␣-␣-3Ј. Fetal hemoglobin (HbF), an ␣ 2 ␥ 2 -tetramer, predominates from week 8 of gestation through birth, after which it is gradually superseded by adult hemoglobin (HbA), an ␣ 2 ␤ 2 -tetramer. HbF is detectable, at approximately 1%, during adult life. The molecular mechanisms underlying the ␥-to ␤-globin switch during development are not fully understood, but are of compelling interest because a persistence of HbF in adults, whether genetic or pharmacologic in origin, is ameliorative in adult ␤-globin gene disorders such as sickle cell anemia or ␤-thalassemia. 1,2 Intermediaries of mammalian metabolism, such as the shortchain fatty acids (SCFAs) butyrate and propionate, are important fuels during fetal life and, when elevated, are implicated in the delayed fetal-to-adult hemoglobin switch in infants of diabetic mothers (butyrate 3 ) and in the elevated HbF levels seen in children with inherited disorders of branched-chain amino acid metabolism (eg, propionic acidemia 4 or ␤-ketothiolase deficiency 5 ). Importantly, therapeutic trials of butyrate in patients with ␤-globin gene disorders have increased ␥-globin gene expression and HbF levels. [6][7][8] Studies of the molecular and cellular effects of SCFAs in erythroid cells have been constrained by the limited number of experimental models currently available. We were interested in finding additional models in which to study the effects of SCFAs on erythropoiesis and on erythroid gene expression. We evaluated the effects of SCFAs on murine erythropoeisis in primitive and definitive erythroid precursor cells from transgenic mice that had endogenous elevations of SCFAs, and in definitive erythroid precursor cells from wt mice and human ␤-globin gene locuscontaining transgenic mice. These studies were undertaken with the expectation that a biologically relevant, primary, definitive erythroid precursor cell model would be an excellent place in which to study the pleiotropic effects of SCFAs on erythropoiesis.The murine ␤-globin gene locus, like the human, is developmentally regulated. ␤ H1 expression is detectable early and persists through embryonic day (E) 12 to 13, while ⑀ y expression is detected later and is present through E13 through 16. 9,10 These embryonic ␤-type globin genes, and the embryonic ␣-like -globin gene, are expressed in large, slowly enucleating, primitive erythroid (EryP) cells from the murine yolk sac. Adult ␤-type globin genes, ␤ Adult , comprise the ␤ maj and ␤ min genes (from the ␤-diffuse haplotype found in most strains) or the ␤ S and ␤ T genes (from the ␤-single haplotype found in the C57/black 6 strain). ␤ Adult and ␣ are expressed primarily in small, rapidly enucleated, definitive erythroid (EryD) cells that arise from the erythroid fetal liver through late gestation and from the adult bone marrow and, in anemic animals, from the adult e...

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Regulation of human colonic cell line proliferation and phenotype by sodium butyrate

Cited by 56 publications

References 46 publications

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Comparative effects of overexpression of p27Kip1 and p21Cip1/Waf1 on growth and differentiation in human colon carcinoma cells

Short-chain fatty acid–mediated effects on erythropoiesis in primary definitive erythroid cells

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