scholarly journals The impact of the RBM4-initiated splicing cascade on modulating the carcinogenic signature of colorectal cancer cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jung-Chun Lin ◽  
Yuan-Chii Lee ◽  
Yu-Chih Liang ◽  
Yang C. Fann ◽  
Kory R. Johnson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Colorectal Cancer Cells ◽  
The Impact

scholarly journals Cortisol and Testosterone Induce Bax and Bcl-2 Gene Expression and Caspases-8 and -9 Activity in Colon Cancer Cells (ht29) and Reduced the Cell Viability

2021 ◽  
Author(s):  
Amin Sarkhosh ◽  
Rahim Ahmadi ◽  
Seyyed Hossein Khatami ◽  
Hadi Ghasemi
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Colorimetric Method ◽  
Caspase 8 ◽  
Activity Levels ◽  
Colon Cancer Cells ◽  
Expression Levels ◽  
Colorectal Cancer Cells ◽  
The Impact

Abstract Cortisol and testosterone can inhibit the proliferation of colorectal cancer cells. Cortisol may augment the anti-cancer activity of testosterone in colorectal cancer cells. This research aimed to assess the impact of cortisol and testosterone on the viability of colon cancer cells (HTCs). The cytotoxic effects of cortisol and testosterone were evaluated using the MTT assay. Bax and Bcl-2 expression levels were determined using real-time PCR. The colorimetric method was used to assess the activity of caspase-8 and -9 enzymes. The expression levels of Bax and Bcl-2 genes significantly increased (p<0.001), as well as the activity levels of caspase-8 and -9, were elevated (p<0.001). Testosterone may exert cytotoxic activity in colon cancer cells in the presence of cortisol, and cortisol and testosterone cotreatment may contribute to the elevated Bax and Bcl-2 genes expression and caspase 8 and 9 activity enhancement in colorectal cancer cells.

scholarly journals The Impact of Molecular Hydrogen on Mitochondrial ROS and Apoptosis in Colorectal Cancer Cells

2021 ◽  
Vol 120 (3) ◽  
pp. 349a
Author(s):  
Yi-Hsuan Tsai ◽  
Megha Jhunjhunwala ◽  
Tsan-Yao Chen ◽  
Chi-Shuo Chen
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Molecular Hydrogen ◽  
Mitochondrial Ros ◽  
Colorectal Cancer Cells ◽  
The Impact

scholarly journals Butyrate Suppresses Glucose Metabolism of Colorectal Cancer Cells via GPR109a-AKT Signaling Pathway and Enhances Chemotherapy

2021 ◽  
Vol 8 ◽  
Author(s):  
Hong-Wei Geng ◽  
Feng-Yi Yin ◽  
Zhi-Fa Zhang ◽  
Xu Gong ◽  
Yun Yang
Keyword(s):  
Colorectal Cancer ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Histone Deacetylases ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Anti Cancer ◽  
Colorectal Cancer Cells ◽  
The Impact

Glycolysis inhibitors are promising therapeutic drugs for tumor treatment, which target the uniquely elevated glucose metabolism of cancer cells. Butyrate is a critical product of beneficial microbes in the colon, which exerts extraordinary anti-cancer activities. In particular, butyrate shows biased inhibitory effects on the cell growth of cancerous colonocytes, whereas it is the major energy source for normal colonocytes. Besides its roles as the histone deacetylases (HDACs) inhibitor and the ligand for G-protein coupled receptor (GPR) 109a, the influence of butyrate on the glucose metabolism of cancerous colonocytes and the underlying molecular mechanism are not fully understood. Here, we show that butyrate markedly inhibited glucose transport and glycolysis of colorectal cancer cells, through reducing the abundance of membrane GLUT1 and cytoplasmic G6PD, which was regulated by the GPR109a-AKT signaling pathway. Moreover, butyrate significantly promoted the chemotherapeutical efficacy of 5-fluorouracil (5-FU) on cancerous colonocytes, with exacerbated impairment of DNA synthesis efficiency. Our findings provide useful information to better understand the molecular basis for the impact of butyrate on the glucose metabolism of colorectal cancer cells, which would promote the development of beneficial metabolites of gut microbiota as therapeutical or adjuvant anti-cancer drugs.

scholarly journals Targeting the tumor metabolism by oxamate potentiates the impact of chemotherapeutics in colorectal cancer cells

2021 ◽  
Author(s):  
Gizem ÇALIBAŞI KOÇAL ◽  
Çağrı ÇAKICI ◽  
Feriha TOKSÖZ ◽  
Şeniz İNANÇ SÜRER ◽  
Tolga SEVER ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Tumor Metabolism ◽  
Colorectal Cancer Cells ◽  
The Impact

scholarly journals IMCA Induces Ferroptosis Mediated by SLC7A11 through the AMPK/mTOR Pathway in Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Lei Zhang ◽  
Wen Liu ◽  
Fangyan Liu ◽  
Qun Wang ◽  
Mengjiao Song ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Screening Tests ◽  
Therapeutic Drug ◽  
Solute Carrier Family ◽  
Colorectal Cancer Cells ◽  
Solute Carrier ◽  
The Impact

Ferroptosis, implicated in several diseases, is a new form of programmed and nonapoptotic cell death triggered by iron-dependent lipid peroxidation after inactivation of the cystine/glutamate antiporter system xc–, which is composed of solute carrier family 7 membrane 11 (SLC7A11) and solute carrier family 3 membrane 2 (SLC3A2). Therefore, inducing ferroptosis through inhibiting the cystine/glutamate antiporter system xc– may be an effective way to treat cancer. In previous screening tests, we found that the benzopyran derivative 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) significantly inhibited the viability of colorectal cancer cells. However, the impact of IMCA on ferroptosis remains unknown. Hence, this study investigated the effect of IMCA on ferroptosis and elucidated the underlying molecular mechanism. Results showed that IMCA significantly inhibited the cell viability of colorectal cancer cells in vitro and inhibited tumor growth with negligible organ toxicity in vivo. Further studies showed that IMCA significantly induced the ferroptosis of colorectal cancer cells. Mechanistically, IMCA downregulated the expression of SLC7A11 and decreased the contents of cysteine and glutathione, which resulted in reactive oxygen species accumulation and ferroptosis. Furthermore, overexpression of SLC7A11 significantly attenuated the ferroptosis caused by IMCA. In addition, IMCA regulated the activity of the AMPK/mTOR/p70S6k signaling pathway, which is related to the activity of SLC7A11 and ferroptosis. Collectively, our research provided experimental evidences on the activity and mechanism of ferroptosis induced by IMCA and revealed that IMCA might be a promising therapeutic drug for colorectal cancer.

scholarly journals The impact of RNA binding motif protein 4-regulated splicing cascade on the progression and metabolism of colorectal cancer cells

Oncotarget ◽  
2015 ◽  
Vol 6 (35) ◽  
pp. 38046-38060 ◽  
Author(s):  
Yu-Chih Liang ◽  
Wei-Cheng Lin ◽  
Ying-Ju Lin ◽  
Jung-Chun Lin
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Rna Binding ◽  
Binding Motif ◽  
Colorectal Cancer Cells ◽  
The Impact

scholarly journals Implications for Ulcerative Colitis and Colorectal Cancer: Role of Pyruvate Kinase M2 in Regulating the Oxidation of Fiber-derived Butyrate in the Diseased Colonocyte (OR04-04-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Dallas Donohoe ◽  
Bohye Park ◽  
Ji Yeon Kim ◽  
Emily Simon ◽  
Haley Porter ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Mitochondrial Function ◽  
Apoptotic Cell ◽  
Conditional Knockout ◽  
Colorectal Cancer Cells ◽  
The Impact

Abstract Objectives Dietary fiber has been proposed to protect against colorectal cancer. Butyrate, a fiber metabolite that is produced by bacteria in the colon, is known to inhibit cell proliferation and promote cell differentiation, while also inducing apoptotic cell death in colorectal cancer cells at physiologically relevant concentrations. Unlike the majority of cells in the human body that prefer utilizing glucose, non-cancerous colonocytes use butyrate as their primary energy source. However, colorectal cancer cells shift away from utilizing butyrate towards glucose (the Warburg effect). A decrease in butyrate utilization by the colonocyte has been reported in ulcerative colitis (UC) and colorectal cancer (CRC). In both of these diseases, the protein called Pyruvate Kinase Isoform M2 (PKM2) is a factor that has been found to be elevated in colonocytes and is known to catalyze a key step in glycolysis. We hypothesize that upregulation of PKM2 in ulcerative colitis and colorectal cancer results in diminished butyrate oxidation, and increased glucose utilization in colonocytes. Methods Mitochondrial function, substrate utilization will be analyzed in several colorectal cell lines, isolated colonocytes, or colonocytes grown in 3-D culture where PKM2 is knocked down, knocked-out, or overexpressed. An in vivo mouse model of colitis will be used to study the impact of PKM2 in the injury and repair process. Results Knockdown of PKM2 in cancerous colonocytes was associated with reduced proliferation and increased apoptosis. Butyrate oxidation was also increased in PKM2 knockdown cells. PKM2 regulated mitochondrial function and impacted the expression of uncoupling proteins (UCPs). Elevated PKM2 in primary colonocytes was associated with diminished butyrate utilization. Finally, conditional knockout of PKM2 in the colon resulted inhibited DSS-induced colitis. Conclusions These results show an important role for PKM2 in promoting ulcerative colitis and colorectal cancer through shifting colonocyte metabolism away from butyrate utilization. Funding Sources University of Tennessee - Start-up Funds.

scholarly journals Silencing PSME3 induces colorectal cancer radiosensitivity by downregulating the expression of cyclin B1 and CKD1

2019 ◽  
Vol 244 (16) ◽  
pp. 1409-1418
Author(s):  
Wen Song ◽  
Cuiping Guo ◽  
Jianxiong Chen ◽  
Shiyu Duan ◽  
Yukun Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Locally Advanced ◽  
Cyclin B1 ◽  
Cancer Prognosis ◽  
Cycle Arrest ◽  
Colorectal Cancer Cells ◽  
The Impact

Resistance to radiotherapy remains a severe obstacle in the treatment of high-risk colorectal cancer patients. Recent studies have indicated that proteasome activator complex subunit 3 (PSME3) participates in the development and progression of various human malignancies and is proposed to play a role in tumor radioresistance. However, the impact of PSME3 on radioresistance of colorectal cancer has been largely unknown. In the present study, the enhanced expression of PSME3 was observed in colorectal cancer cells and tissue. Upregulation of PSME3 was significantly implicated in lymph node state, lymphovascular invasion, and Dukes' stage. Furthermore, high PSME3 expression was closely linked to poorer overall and progression-free survival in patients with colorectal cancer. The study further demonstrated that the proliferative, invasive and migratory potential of colorectal cancer cells was effectively inhibited in vitro after silencing PSME3. Our results verified that knockdown of PSME3 probably triggered cell cycle arrest at the G2/M phase by downregulation of cyclinB1 and CDK1, thereby enhancing the radiosensitivity of colorectal cancer cells. These data illustrated that PSME3 is a promising biomarker predictive of colorectal cancer prognosis and silencing of PSME3 may provide with a new approach for sensitizing the radiotherapy in colorectal cancer. Impact statement It is reported that colorectal cancer (CRC) is the third most common cancer worldwide and the fourth leading cause of cancer-related death. At present, the main treatment method of colorectal cancer is surgery, supplemented by radiotherapy and chemotherapy. Among them, radiotherapy plays an important role in the treatment of locally advanced colorectal cancer, surgery, and chemotherapy. Our study found that down-regulation of PSME3 may enhance the radiosensitivity of CRC cells by triggering cell cycle arrest, which suggests that silence PSME3 may provide a new method for improving the radiosensitivity of CRC. What’more, our research also demonstrated that PSME3 may promote proliferation, invasive and migratory potential of CRC cells, which implies that PSME3 might be a biomarker of CRC for early diagnosis and treatment.

scholarly journals Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells

Glycobiology ◽  
2018 ◽  
Vol 29 (2) ◽  
pp. 137-150 ◽  
Author(s):  
Athanasios Blanas ◽  
Lenneke A M Cornelissen ◽  
Maximilianos Kotsias ◽  
Joost C van der Horst ◽  
Henri J van de Vrugt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cancer Cells ◽  
Transcriptional Activation ◽  
De Novo ◽  
Colorectal Cancer Cell Line ◽  
Oncology Research ◽  
Colorectal Cancer Cells ◽  
Specific Regulation ◽  
The Impact

AbstractAberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy. Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9). However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells. Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes. For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system. Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface. Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes. Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants. In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.

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