Anti-mitogenic and apoptotic effects of 5-HT1B receptor antagonist on HT29 colorectal cancer cell line

Ataee, Ramin; Ajdary, Soheila; Zarrindast, Mohammad‐Reza; Rezayat, Mehdi; Hayatbakhsh, Mohammad R.

doi:10.1007/s00432-010-0801-3

Cited by 34 publications

(28 citation statements)

References 27 publications

(48 reference statements)

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“…It has been previously shown that different 5-HT receptors can trigger the proliferative properties of 5-HT and mediate cascades of mitogenic signaling pathways [67]. The stimulation of 5-HT receptors leads to transcription factors phosphorylation and cell division activation, which is a common reaction to many extracellular stimuli, including growth factors, hormones and neurotransmitters in mammalian cells, such as human pancreatic carcinoid, and mouse fibroblast cells [68], [69]. In prostate cancer, these growth factors act on the adjacent (exocrine) tumor cells to enhance tumor growth, differentiation and angiogenesis, the events that lead to a poor prognosis [18], [70].…”

Section: Discussionmentioning

confidence: 99%

“…In prostate cancer, these growth factors act on the adjacent (exocrine) tumor cells to enhance tumor growth, differentiation and angiogenesis, the events that lead to a poor prognosis [18], [70]. Recently, 5-HT 1B receptors were associated with an increased proliferation index, correlated with the size of the tumor in hepatocellular cancer patients [71], and were shown to play a potential role in colorectal cancer [69]. Since we showed here that the 5-HT 1B and 5-HT 1D receptors are highly over-expressed in PaCa cells, we tried to explore the etiological associations between its expression and PaCa progression.…”

Section: Discussionmentioning

confidence: 99%

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Down-Regulation of 5-HT1B and 5-HT1D Receptors Inhibits Proliferation, Clonogenicity and Invasion of Human Pancreatic Cancer Cells

et al. 2014

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Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa) patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT) contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA), induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT), concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B– and 5-HT1D–mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification, and valuable new therapeutic targets for managing pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Down-Regulation of 5-HT1B and 5-HT1D Receptors Inhibits Proliferation, Clonogenicity and Invasion of Human Pancreatic Cancer Cells

et al. 2014

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“…In relation to cancer the role of HTR1B is less defined. A few in vitro studies suggest apoptotic and antiproliferative properties of HTR1B antagonists (28,29).…”

Section: Discussionmentioning

confidence: 99%

Expression of Serotonin Receptors in Human Hepatocellular Cancer

Soll¹,

Riener²,

Oberkofler³

et al. 2012

Clinical Cancer Research

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Purpose: Serotonin is a well-known neurotransmitter and vasoactive substance. Recent research indicates that serotonin contributes to liver regeneration and promotes tumor growth of human hepatocellular cancer. The aim of this study is to investigate the expression of serotonin receptors in hepatocellular cancer and analyze their potential as a cytotoxic target.Experimental Design: Using a tissue microarray and immunohistochemistry, we analyzed the expression of serotonin receptors in the liver from 176 patients with hepatocellular carcinoma, of which nontumor tissue was available in 109 patients. Relevant clinicopathologic parameters were compared with serotonin receptor expression. Two human hepatocellular cancer cell lines, Huh7 and HepG2, were used to test serotonin antagonists as a possible cytotoxic drug.Results: The serotonin receptors 1B and 2B were expressed, respectively, in 32% and 35% of the patients with hepatocellular cancer. Both receptors were associated with an increased proliferation index, and receptor 1B correlated with the size of the tumor. Serotonin antagonists of receptors 1B and 2B consistently decreased viability and proliferation in Huh7 and HepG2 cell lines.Conclusion: We identified two serotonin receptors that are often overexpressed in human hepatocellular cancer and may serve as a new cytotoxic target.

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“…It is also remarkable that when using cell cultures, the expression of a particular receptor may depend on the degree of cell differentiation and the growing conditions. Recently, the presence of opioid, serotonin, muscarinic, PPARβ/δ receptors has been reported in this cell line (Zoghbi et al 2006 ;Ataee et al 2010 ;Belo et al 2011 ;Foreman et al 2011 ). Information on the studies on receptors carried out in this cell line can be found at Zweibaum et al ( 2011 ).…”

Section: Relevance To Human In Vivo Situationmentioning

confidence: 98%

HT29 Cell Line

Martínez-Maqueda

Miralles

Recio

2015

The Impact of Food Bioactives on Health

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The human colon adenocarcinoma cell line HT29, is not only used to study the biology of human colon cancers, but it is receiving special interest in studies focused on food digestion and bioavailability due to the ability to express characteristics of mature intestinal cells. In the differentiated phenotype, they are able to form a monolayer with tight junctions between cells and a typical apical brush border. In addition, these differentiated cells express brush-border-associated hydrolases typical of the small intestine although the enzymatic activity is lower than that found in vivo. Although they represent a valuable model due to their similarities with enterocytes of the small intestine, their limitations and the relevance to the in vivo situation are also considered in this chapter. The application of this cell line to transport studies of drugs and food compounds is illustrated, especially when the effect of the mucus layer is considered or used as co-culture in combination with Caco-2 cells. They have also been frequently used to study the intestinal immune response to bacterial infection, and microorganism survival, adhesion or invasion. Finally, the use of these cells to evaluate the effect of several food compounds and mucin secretion is summarized. Keywords HT29 • Cell differentiation • Transport studies • Intestinal cell OriginThe human colon adenocarcinoma cell line HT29 was isolated from a primary tumor of a 44 years old Caucasian female in 1964 by Fogh and Trempe ( 1975 ). Since then, many cell lines have been derived from human colon cancers. Initially, this cell line was used to study different aspects of the biology of human cancers. However, these cells have attracted attention due to the fact they were able to express characteristics of mature intestinal cells, such as enterocytes or mucus producing cells.

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Anti-mitogenic and apoptotic effects of 5-HT1B receptor antagonist on HT29 colorectal cancer cell line

Abstract: The findings of this study provide evidence for the potential role of 5-HT(1B) receptor in colorectal cancer. Further investigation is required to explore the effect of receptor antagonists on the prevention, prognosis and treatment of patients with colorectal cancer.

Cited by 34 publications

References 27 publications

Down-Regulation of 5-HT1B and 5-HT1D Receptors Inhibits Proliferation, Clonogenicity and Invasion of Human Pancreatic Cancer Cells

Down-Regulation of 5-HT1B and 5-HT1D Receptors Inhibits Proliferation, Clonogenicity and Invasion of Human Pancreatic Cancer Cells

Expression of Serotonin Receptors in Human Hepatocellular Cancer

HT29 Cell Line

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