Activation of protein kinase C augments butyrate-induced differentiation and turnover in human colonic epithelial cells in vitro

Rickard, Kurt L.; Young, Graeme P.; Phillips, Wayne A.

doi:10.1093/carcin/20.6.977

Cited by 29 publications

(26 citation statements)

References 33 publications

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“…Our experiments suggest that these agents act via different mechanisms since PMA-induced PMCA4b upregulation was abrogated by a PKC inhibitor while SCFAinduced upregulation was only slightly modified by PKC inhibition. Similarly to our findings in MCF-7 cells, PMA augmented butyrate-induced differentiation in colon cancer cells but the butyrate-induced differentiation was not inhibited by PKC inhibitors [48]. A more recent study also proves that butyrate-induced cellular processes can be potentiated by PMA.…”

Section: Discussionsupporting

confidence: 89%

“…All treatments resulted in a great increase in the population of Oil Red O positive cells so that the area of lipid droplets per cell increased 9-15 fold in SCFA-treated cells compared to control. Previous studies showed that SCFA and PMA treatments acted synergistically in colon cancer [48] and intestinal epithelial cells [49], therefore, we tested the differentiation status of MCF-7 cells treated with SCFAs in combination with PMA. We found that PMA greatly potentiated the differentiation process induced by valerate ( Fig.…”

Section: Effects Of Scfas and Pma On Cellular Proliferation And Diffementioning

confidence: 99%

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Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

et al. 2014

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The expression of the plasma membrane Ca 2+ ATPase (PMCA) isoforms is altered in several types of cancer cells suggesting that they are involved in cancer progression. In this study we induced differentiation of MCF-7 breast cancer cells by histone deacetylase inhibitors (HDACis) such as short chain fatty acids (SCFAs) or suberoylanilide hydroxamic acid (SAHA), and by phorbol 12-myristate 13-acetate (PMA) and found strong upregulation of PMCA4b protein expression in response to these treatments. Furthermore, combination of HDACis with PMA augmented cell differentiation and further enhanced PMCA4b expression both at mRNA and protein levels. Immunocytochemical analysis revealed that the upregulated protein was located mostly in the plasma membrane. To examine the functional consequences of elevated PMCA4b expression, the characteristics of intracellular Ca 2+ signals were investigated before and after differentiation inducing treatments, and also in cells overexpressing PMCA4b. The increased PMCA4b expression -either by treatment or overexpression -led to enhanced Ca 2+ clearance from the stimulated cells. We found pronounced PMCA4 protein expression in normal breast tissue samples highlighting the importance of this pump for the maintenance of mammary epithelial Ca 2+ homeostasis. These results suggest that modulation of Ca 2+ signaling by enhanced PMCA4b expression may contribute to normal development of breast epithelium and may be lost in cancer.3

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Section: Discussionsupporting

confidence: 89%

Section: Effects Of Scfas and Pma On Cellular Proliferation And Diffementioning

confidence: 99%

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

et al. 2014

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“…Experimental conditions (PMA concentration, absence of serum and time of incubation) were assessed based on data from the literature 25 and on our own experience (unpublished data). In the present experiment, serum was omitted to avoid activation of PKC by other exogenous stimuli.…”

Section: Modulation Of Classical Protein Kinase C Activity Alters Thementioning

confidence: 99%

Expression of protein kinase C ?1 confers resistance to TNF?- and paclitaxel-induced apoptosis in HT-29 colon carcinoma cells

Cesaro¹,

Raiteri²,

Démoz³

et al. 2001

Int. J. Cancer

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The expression of different protein kinase C (PKC) isoenzymes has been shown to vary with proliferation rates, differentiation or apoptosis in normal colon crypts. In addition, the activity of some PKC isoenzymes appears to be reduced in colorectal cancer. The aim of the present work was to determine whether modulation of PKC expression would affect the susceptibility of a p53-defective colon carcinoma cell line to different apoptotic treatments. HT-29 cells exhibited sensitivity to paclitaxel (Taxol) and tumor necrosis factor ␣ (TNF␣) in a dose-and time-dependent manner but were relatively resistant to etoposide. Inhibition of PKC activity augmented the susceptibility of HT-29 cells to apoptosis, and phorbol ester induction of PKC reduced such susceptibility. Key words: protein kinase C; TNF␣; paclitaxel; apoptosis; colon carcinomaColorectal cancer is one of the most common solid tumors world-wide. Due to its high metastatic potential and the frequent onset of resistance to chemotherapy, it is one of the four major causes of death by neoplasia in westernized countries. Loss of function of p53 occurs in more than 75% of human colorectal cancers. Since p53 regulates a complex array of cellular responses to DNA damage, including cell cycle arrest and apoptosis, its loss of function is also expected to affect the sensitivity of tumor cells to DNA-damaging antiblastic drugs. 1,2The expression of different protein kinase C (PKC) isoenzymes varies with proliferation rates, differentiation or apoptosis in normal colon crypts, [3][4][5][6] and the activity of some PKC isoenzymes is reduced in colorectal cancer. [7][8][9] Whether, in addition to loss of function of p53, altered functioning of PKCs contributes to the low sensitivity of colon carcinomas to apoptosis-based chemotherapy remains to be established. In the present work we addressed this issue by examining the effect of various apoptotic treatments on HT-29 colon cancer cells that lack functional p53 10 and either do or do not express abnormal levels of the isoform ␤1 of PKC. We found that paclitaxel (Taxol) and TNF␣, but not etoposide, efficiently induced apoptosis of HT-29 cells in a dose-and timedependent manner.The involvement of PKC in the apoptotic pathways triggered by paclitaxel or TNF␣ was assessed by using a myristoylated pseudosubstrate as inhibitor at doses not affecting cell viability. In HT-29 cells, inhibition of PKC (␣ and ␤ isoforms) activity augmented by twofold the cytotoxicity of both drugs. Induction of PKC by the phorbol ester phorbol myristate acetate (PMA) decreased the susceptibility of HT-29 cells to both TNF␣ and paclitaxel treatments. Resistance to apoptotic treatments was consistently observed in transfected HT-29 cells hyper-expressing PKC␤1. The present data implicate PKC (␣ and ␤) as a component of the mechanism responsible for the resistance of colon carcinoma cells to apoptotic drugs. MATERIAL AND METHODS Cells and chemicalsThe HT-29 human colon cancer cell line was obtained from the American Type Culture Collection (ATCC, Rock...

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“…In studies with solid tumors, TPA was shown to inhibit the growth, stimulate apoptosis, or enhance differentiation in human tumor cell lines derived from patients with melanoma or prostate, breast, colon, or lung cancer (15)(16)(17)(18)(19). Treatment of prostate cancer LNCaP cells with clinically achievable concentrations of TPA (1-1.6 nM) resulted in growth inhibition (15, 20 -22), and treatment of these cells with a severalfold higher concentration of TPA caused apoptosis (15, 20 -22).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of 12- O -Tetradecanoylphorbol-13-acetate Alone or in Combination with All- trans -Retinoic Acid on the Growth of LNCaP Prostate Tumors in Immunodeficient Mice

et al. 2004

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The percentage of animals with some tumor regression after 21 days of treatment was 0% for the control group, 31% for the ATRA group, 62% for the TPA group, and 100% for the TPA؉ATRA group (13 mice/ group). Although treatment of the mice with TPA or TPA؉ATRA continued to inhibit tumor growth for the duration of the 46-day study, treatment of the mice with ATRA alone did not inhibit tumor growth beyond 28 days of daily injections (6 mice/group). Mechanistic studies indicated that treatment of the mice with TPA or TPA؉ATRA for 46 days increased apoptosis in the tumors, and treatment with TPA؉ATRA also decreased the mitotic index. Because the dose of TPA used in this study was effective and resulted in clinically achievable blood levels, clinical trials with TPA alone or in combination with ATRA in patients with prostate cancer may be warranted.

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Activation of protein kinase C augments butyrate-induced differentiation and turnover in human colonic epithelial cells in vitro

Cited by 29 publications

References 33 publications

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

Expression of protein kinase C ?1 confers resistance to TNF?- and paclitaxel-induced apoptosis in HT-29 colon carcinoma cells

Inhibitory Effect of 12- O -Tetradecanoylphorbol-13-acetate Alone or in Combination with All- trans -Retinoic Acid on the Growth of LNCaP Prostate Tumors in Immunodeficient Mice

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