Heavy metal pollutant cadmium enhances malignant biological behavior of human colorectal carcinoma HCT-116 cells via inducing epithelial-mesenchymal transition

Carnosine is an endogenous dipeptide found in the vertebrate skeletal muscles that is usually obtained through the diet. To investigate the mechanism by which carnosine regulates the migration and intravasation of human colorectal cancer (CRC) cells, we used cultured HCT-116 cells as an experimental model in this study. We examined HCT-116 cell migratory and intravasive abilities and expression of epithelial-mesenchymal transition (EMT)-associated molecules and matrix metalloproteinases (MMPs) after carnosine treatment. The results showed that both migration and invasion were inhibited in cells treated with carnosine. We found significant decreases in Twist-1 protein levels and increases in E-cadherin protein levels in HCT-116 cells after carnosine exposure. Although plasminogen activator (uPA) and MMP-9 mRNA and protein levels were decreased, TIMP-1 mRNA and protein levels were increased. Furthermore, the cytosolic levels of phosphorylated I[Formula: see text]B (p-I[Formula: see text]B) and NF-[Formula: see text]B DNA-binding activity were reduced after carnosine treatment. These results indicate that carnosine inhibits the migration and intravasation of human CRC cells. The regulatory mechanism may occur by suppressing NF-[Formula: see text]B activity and modulating MMP and EMT-related gene expression in HCT-116 cells.

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20( S )‐Protopanaxadiol inhibits epithelial‐mesenchymal transition by promoting retinoid X receptor alpha in human colorectal carcinoma cells

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.16054 ◽

2020 ◽

Vol 24 (24) ◽

pp. 14349-14365

Author(s):

Zeyuan Lu ◽

Hongyan Liu ◽

Wenwen Fu ◽

Yuchen Wang ◽

Jianan Geng ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Retinoid X Receptor ◽

Carcinoma Cells ◽

Mesenchymal Transition ◽

Receptor Alpha ◽

Human Colorectal Carcinoma ◽

Retinoid X Receptor Alpha

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Pien Tze Huang Overcomes Multidrug Resistance and Epithelial-Mesenchymal Transition in Human Colorectal Carcinoma Cells via Suppression of TGF-βPathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/679436 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 14

Author(s):

Aling Shen ◽

Hongwei Chen ◽

Youqin Chen ◽

Jiumao Lin ◽

Wei Lin ◽

...

Keyword(s):

Multidrug Resistance ◽

Colorectal Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Carcinoma Cells ◽

Migration And Invasion ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Folk Remedy ◽

Pien Tze Huang ◽

Human Colorectal Carcinoma

The traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used as a folk remedy for cancer. To elucidate the mode of action of PZH against cancer, in the present study we used a 5-FU resistant human colorectal carcinoma cell line (HCT-8/5-FU) to evaluate the effects of PZH on multidrug resistance (MDR) and epithelial-mesenchymal transition (EMT) as well as the activation of TGF-βpathway. We found that PZH dose-dependently inhibited the viability of HCT-8/5-FU cells which were insensitive to treatment of 5-FU and ADM, demonstrating the ability of PZH to overcome chemoresistance. Furthermore, PZH increased the intercellular accumulation of Rhodamine-123 and downregulated the expression of ABCG2 in HCT-8/5-FU cells. In addition, drug resistance induced the process of EMT in HCT-8 cells as evidenced by EMT-related morphological changes and alteration in the expression of EMT-regulatory factors, which however was neutralized by PZH treatment. Moreover, PZH inhibited MDR/EMT-enhanced migration and invasion capabilities of HCT-8 cells in a dose-dependent manner and suppressed MDR-induced activation of TGF-βsignaling in HCT-8/5-FU cells. Taken together, our study suggests that PZH can effectively overcome MDR and inhibit EMT in human colorectal carcinoma cells via suppression of the TGF-βpathway.

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LYG-202 inhibits the proliferation of human colorectal carcinoma HCT-116 cells through induction of G1/S cell cycle arrest and apoptosis via p53 and p21WAF1/Cip1 expression

Biochemistry and Cell Biology ◽

10.1139/o10-162 ◽

2011 ◽

Vol 89 (3) ◽

pp. 287-298 ◽

Cited By ~ 12

Author(s):

Wei Liu ◽

Qinsheng Dai ◽

Na Lu ◽

Libin Wei ◽

Jun Ha ◽

...

Keyword(s):

Cell Cycle ◽

Colorectal Carcinoma ◽

Cell Cycle Arrest ◽

Caspase 3 ◽

Down Regulation ◽

Transfected Cells ◽

Cycle Arrest ◽

Hct 116 ◽

Human Colorectal Carcinoma ◽

Hct 116 Cells

We recently established that LYG-202, a new flavonoid with a piperazine substitution, exerts an anti-tumor effect in vivo and in vitro. In the present study, we demonstrate that LYG-202 induces G1/S phase arrest and apoptosis in human colorectal carcinoma HCT-116 cells. Data showed that the blockade of the cell cycle was associated with increased p21WAF1/Cip1 and Rb levels and reduced expression of cyclin D1, cyclin E, and CDK4. Moreover, PARP cleavage, activation of caspase-3, caspase-8, and caspase-9, and an increased ratio of Bax/Bcl-2 were detected in LYG-202-induced apoptosis. Additionally, activation of p53 resulted in the up-regulation of its downstream targets PUMA and p21WAF1/Cip1, as well as the down-regulation of its negative regulator MDM2, suggesting that the p53 pathway may play a crucial role in LYG-202-induced cell cycle arrest and apoptosis. Furthermore, siRNA knockdown of p53 attenuated the G1 cell cycle arrest and apoptosis induced by LYG-202, as the effects of LYG-202 on up-regulation of p21WAF1/Cip1 and down-regulation of Bcl-2 and pro-caspase-3 were partly inhibited in p53 siRNA transfected cells compared with control siRNA transfected cells. Collectively, these data indicate that LYG-202 exerts its anti-tumor potency by activating the p53–p21 pathway for G1/S cell cycle arrest and apoptosis in colorectal cancer cells.

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