PPAR  is involved in mesalazine-mediated induction of apoptosis and inhibition of cell growth in colon cancer cells

Schwab, Markus; Reynders, Veerle; Loitsch, Stefan; Shastri, Yogesh M.; Steinhilber, Dieter; Schröder, Oliver; Stein, Jiirgen

doi:10.1093/carcin/bgn118

Cited by 61 publications

(45 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Only recently was this phenomenon demonstrated using mesalazine, which promotes c-myc downregulation by stimulating HT-29 cells, rendering this drug anti-proliferative and anti-carcinogenic [8]. Specific downregulation of c-myc could therefore play a role in a potential therapeutic strategy against human cancers, including colon cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that c-myc is significant in cellular proliferation and cell growth [6,8,14]. Thus, the high levels of c-myc seen in colon tumors give a probable growth advantage.…”

Section: The Proliferation Of Ht-29 and Imr-32 Cells After The Sirna mentioning

confidence: 99%

“…The members of the myc proto-oncogene family, c-, L-, and N-myc, are thought to be central regulators of cell growth, and deregulated myc expression is associated with many cancers, including colon cancer [3][4][5]. c-myc is believed to participate in most aspects of cellular function, including replication, growth, metabolism, differentiation, and apoptosis [6][7][8]. A frequent genetic abnormality seen in colon cancer is the elevated expression of c-myc [4,9].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The knockdown of c-myc expression by RNAi inhibits cell proliferation in human colon cancer HT-29 cells in vitro and in vivo

Zhang

Tian

2009

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

Abstract:We investigated the effects of RNA interference-mediated silencing of the c-myc gene on celluar proliferation and apoptosis in human colon cancer HT-29 cells in vitro and in vivo. A small interfering RNA (siRNA) targeting c-myc was designed, the DNA template was synthesized, and the siRNA was obtained by in vitro transcription. After siRNA transfection into HT-29 and human neuroblastoma IMR-32 cells with Lipofectamine 2000 TM , the proliferation of the HT-29 and IMR-32 cells was assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetry, and Hoechst 33258 staining was used to observe cell apoptosis. Following gene transfer to HT-29 cells, the expression of c-myc mRNA was examined via reverse transcription polymerase chain reaction, and the level of the protein via Western blot assay. Growth curves were constructed and in vivo experiments were performed on nude mice to assess the effects of c-myc silencing on tumor growth. The c-myc expression in the tumor tissue was measured by reverse transcription polymerase chain reaction and subsequently by immunohistochemistry. Our paper demonstrates that the delivery of siRNA directed against c-myc not only efficiently down-regulated the expression of c-myc, inhibited the proliferation of HT-29 cells and induced apoptosis in vitro, but also suppressed the growth of colon cancer cells in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: The Proliferation Of Ht-29 and Imr-32 Cells After The Sirna mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The knockdown of c-myc expression by RNAi inhibits cell proliferation in human colon cancer HT-29 cells in vitro and in vivo

Zhang

Tian

2009

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

show abstract

“…Moreover, the roles of PPARγ in various stages of CRC are also poorly understood. One recent study demonstrated that activation of PPARγ inhibited cell growth and induced cell differentiation in human colorectal cancer through several pathways involving the induction of PTEN over-expression (7). PTEN undergoes genetic or epigenetic inactivation in many malignancies including colorectal cancer (8,9).…”

Section: Introductionmentioning

confidence: 99%

Expression of PPARγ and PTEN in human colorectal cancer: An immunohistochemical study using tissue microarray methodology

et al. 2011

View full text Add to dashboard Cite

Abstract. Although aberrations of peroxisome proliferatoractivated receptor γ (PPARγ) and phosphatase and tensin homolog (PTEN) expression have been identified in several other cancer types, certain previous studies have revealed that PPARγ is abundant in normal and malignant tissue in the colon. The question of whether aberrant PTEN is involved in the initial stage or is a later event during colorectal carcinogenesis remains controversial. Relatively few studies have focused on the correlation of expression of PPARγ and PTEN in various tissues. In the present study, paraffin-embedded blocks from 139 patients with CRC, 18 adenomatous polyps and 50 paired paracancerous benign mucosas were selected and analysed in 4 tissue microarray (TMA) blocks comprising 104, 72, 130 and 54 cores, respectively. Expression of PPARγ and PTEN was examined using immunohistochemical staining on TMAs. There were no significant differences in the expression of PPARγ (P=0.055) and PTEN (P=0.100) between the colorectal cancers, adenomas and paracancerous mucosas. However, correlations of PPARγ expression with clinical stage (P=0.004) and PTEN expression with histological grade (P=0.006) and distant metastasis (P=0.015) were demonstrated in the CRC specimens. Although the differences in PPARγ and PTEN protein expression in human colorectal cancer may not be considered as early diagnostic markers, our results indicate that CRCs with a low expression or deletion of PTEN may progress towards invasion and even metastasis; thus, PTEN may have potential as a prognostic marker in human CRC.

show abstract

“…Beside the anti inflammatory properties of PPARc this nuclear receptor regulates cell proliferation, differentiation and is able to induce apoptosis [95]. Activation of PPARc by a syn thetic ligand (mesalasine) has been shown to inhibit cancer growth by decreasing cell proliferation and increase cell apoptosis [96]. Since a decrease of PPARc expression has been observed in some patients bearing CRC [97], a decrease in local GCs production in these patients may be involved, but no data are presently available.…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 99%

Intestinal steroidogenesis

et al. 2015

View full text Add to dashboard Cite

a b s t r a c tSteroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs. According to these studies, the intestine appears to be a major source of de novo produced glucocorticoids as well as a tissue capable of producing and metabolizing sex steroids. This finding is based on the detection of ste roidogenic enzyme expression as well as the presence of bioactive steroids in both the rodent and human gut. Within the intestinal mucosa, the intestinal epithelial cell layer is one of the main cellular sources of steroids. Glucocorticoid synthesis regulation in the intestinal epithelial cells is unique in that it does not involve the classical positive regulator steroidogenic factor 1 (SF 1) but a closely related homolog, namely the liver receptor homolog 1 (LRH 1). This local production of immunoregulatory glucocorticoids contributes to intestinal homeostasis and has been linked to pathophysiology of inflammatory bowel dis eases. Intestinal epithelial cells also possess the ability to metabolize sex steroids, notably estrogen; this mechanism may impact colorectal cancer development. In this review, we contextualize and discuss what is known about intestinal steroidogenesis and regulation as well as the key role these functions play both in physiological and pathological conditions.

show abstract

PPAR is involved in mesalazine-mediated induction of apoptosis and inhibition of cell growth in colon cancer cells

Abstract: This study clearly demonstrates that mesalazine-mediated pro-apoptotic and anti-proliferative actions are regulated via PPARgamma-dependent and -independent pathways in colonocytes.

Cited by 61 publications

References 54 publications

The knockdown of c-myc expression by RNAi inhibits cell proliferation in human colon cancer HT-29 cells in vitro and in vivo

The knockdown of c-myc expression by RNAi inhibits cell proliferation in human colon cancer HT-29 cells in vitro and in vivo

Expression of PPARγ and PTEN in human colorectal cancer: An immunohistochemical study using tissue microarray methodology

Intestinal steroidogenesis

Contact Info

Product

Resources

About