Synergistic role of Caspase-8 and Caspase-3 expressions: Prognostic and predictive biomarkers in colorectal cancer

2018 ◽  
Vol 21 (4) ◽  
pp. 899-908 ◽  
Author(s):  
Qiang Yao ◽  
Weimin Wang ◽  
Jun Jin ◽  
Ke Min ◽  
Jian Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Caspase 3 ◽  
Predictive Biomarkers ◽  
Caspase 8

scholarly journals Antiproliferative and Apoptotic Effects of Red Beetroot and Betanin on Human Colorectal Cancer Cell Lines

2021 ◽  
Author(s):  
Amir Saber ◽  
Nasim Abedimanesh ◽  
Mohammad-Hossein Somi ◽  
Ahmad Yari Khosroushahi
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Alcoholic Extract ◽  
Caspase 9 ◽  
Dapi Staining ◽  
Normal Cells ◽  
Colorectal Cancer Cell Lines ◽  
Ht 29

Abstract Background: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Fruit and vegetables have some active compounds such as flavonoids and polyphenols that protect against malignancies through their antioxidative, anti-inflammatory, anti-proliferative, neuro, and hepatoprotective properties. Red beetroot (Beta vulgaris) contains red (betacyanins) and yellow (betaxanthins) pigments known as betalains. Betanin makes up 75-95% of the total betacyanins, possessed a wide range of favorable biological effects such as chemopreventive, anticarcinogenic, anti-tumorogenic, antiangiogenic, and proapoptotic effects. Methods: Red beetroot hydro-alcoholic extract and betanin were used to treat Caco-2 and HT-29 colorectal cancer cells, as well as KDR/293 normal epithelial cells. The half-maximal inhibitory concentration (IC50) was determined by prescreening MTT tests in the range of 20 to 140 µg/ml at 24 and 48 h. The cytotoxicity and apoptosis-inducing evaluations were performed via MTT assay, DAPI staining, and FACS-flow cytometry tests using determined times and doses. Moreover, the expression level of six important genes involving in the apoptosis pathway (Bcl-2, BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) were determined using the real-time polymerase chain reaction (RT-PCR) method.Results: The IC50 doses for HT-29 and Caco-2 cell lines were determined to be about 92 μg/mL, 107 μg/mL for beetroot hydro-alcoholic extract, and 64 μg/mL, 90 μg/mL for betanin at 48 h, respectively. Our findings showed that beetroot extract and betanin significantly inhibit the growth of HT-29 and Caco-2 cell lines, time and dose-dependently, without considerable adverse effects on KDR/293 normal cells. Moreover, DAPI staining and flow cytometry results revealed significant apoptosis symptoms in treated cancerous cell lines. The expression level of pro-apoptotic genes involved in intrinsic and extrinsic apoptosis pathways (BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) in treated HT-29 and Caco-2 cells was higher than untreated and normal cells, whereas the anti-apoptotic gene (Bcl-2) was downregulated. Conclusion: Beetroot hydro-alcoholic extract and betanin significantly inhibited cell proliferation and induced cell apoptosis (intrinsic and extrinsic pathways) via modification of effective genes in both colorectal cancer cell lines with no significant cytotoxic effects on KDR/293 normal cells. The mechanism of the anticancer effects of red beetroot extract and betanin needs to be further studied.

scholarly journals Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice

2021 ◽  
Vol 11 ◽  
Author(s):  
Eleonora Lai ◽  
Stefano Cascinu ◽  
Mario Scartozzi
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Vascular Endothelial ◽  
The Novel ◽  
Second Line ◽  
Endothelial Growth Factor

Targeting tumor-driven angiogenesis is an effective strategy in the management of metastatic colorectal cancer (mCRC); however, the choice of second-line therapy is complicated by the availability of several drugs, the occurrence of resistance and the lack of validated prognostic and predictive biomarkers. This review examines the use of angiogenesis-targeted therapies for the second-line management of mCRC patients. Mechanisms of resistance and anti-placental growth factor agents are discussed, and the role of aflibercept, a recombinant fusion protein consisting of portions of human vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2, is highlighted. The novel mechanism of action of aflibercept makes it a useful second-line agent in mCRC patients progressing after oxaliplatin-based chemotherapy, as well as in those with resistance after bevacizumab.

scholarly journals The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer

2019 ◽  
Vol 9 (1) ◽  
pp. 5 ◽  
Author(s):  
David Hermel ◽  
Darren Sigal
Keyword(s):  
Colorectal Cancer ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Current Data ◽  
Inhibitor Therapy ◽  
Immunomodulatory Agents ◽  
Checkpoint Inhibitor Therapy ◽  
Microsatellite Stability

Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit in patients with colorectal cancer has been generally limited to tumors with loss of mismatch repair function and those with specific germline mutations in the DNA polymerase gene. Unfortunately, tumors with these specific mutator phenotypes are in the minority. Recent pre-clinical and clinical studies have begun to reveal encouraging results suggesting that checkpoint inhibitor therapy can be expanded to an increasing number of colorectal tumors with microsatellite stability and the absence of traditional predictive biomarkers of checkpoint inhibitor response. These studies generally rely on combinations of checkpoint inhibitors with chemotherapy, molecular targeted therapy, radiation therapy, or other novel immunomodulatory agents. This article will review the most current data in microsatellite stable colorectal cancer.

scholarly journals Role of Insulin Receptor and Balance in Insulin Receptor Isoforms A and B in Regulation of Apoptosis in Simian Virus 40-immortalized Neonatal Hepatocytes

2008 ◽  
Vol 19 (3) ◽  
pp. 1185-1198 ◽  
Author(s):  
Carmen Nevado ◽  
Manuel Benito ◽  
Angela M. Valverde
Keyword(s):  
Insulin Receptor ◽  
Caspase 3 ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Caspase 8 ◽  
Death Domain ◽  
Cytochrome C Release ◽  
Insulin Receptor Isoforms ◽  
Neonatal Hepatocytes

We have investigated the unique role of the insulin receptor (IR) and the balance of its isoforms A and B in the regulation of apoptosis in simian virus 40 (SV40)-immortalized neonatal hepatocytes. Immortalized hepatocytes lacking (HIR KO) or expressing the entire IR (HIR LoxP), and cells expressing either IRA (HIR RecA) or IRB (HIR RecB) have been generated. IR deficiency in hepatocytes increases sensitivity to the withdrawal of growth factors, because these cells display an increase in reactive oxygen species, a decrease in Bcl-xL, a rapid accumulation of nuclear Foxo1, and up-regulation of Bim. These events resulted in acceleration of caspase-3 activation, DNA laddering, and cell death. The single expression of either IRA or IRB produced a stronger apoptotic phenotype. In these cells, protein complexes containing IRA or IRB and Fas/Fas-associating protein with death domain activated caspase-8, and, ultimately, caspase-3. In hepatocytes expressing IRA, Bid cleavage and cytochrome C release were increased whereas direct activation of caspase-3 by caspase-8 and a more rapid apoptotic process occurred in hepatocytes expressing IRB. Conversely, coexpression of IRA and IRB in IR-deficient hepatocytes rescued from apoptosis. Our results suggest that balance alteration of IRA and IRB may serve as a ligand-independent apoptotic trigger in hepatocytes, which may regulate liver development.

A Crucial Role of Caspase 3 and Caspase 8 in Paclitaxel-Induced Apoptosis

1999 ◽  
Vol 2 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Haruki Oyaizu ◽  
Yasushi Adachi ◽  
Shigeru Taketani ◽  
Rikio Tokunaga ◽  
Shirou Fukuhara ◽  
...  
Keyword(s):  
Crucial Role ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Induced Apoptosis

scholarly journals Salmonella enterica serovar Typhimurium sseK3 induces apoptosis and enhances glycolysis in macrophages

2020 ◽  
Author(s):  
Chuan Yu ◽  
Fuyu Du ◽  
Chunjie Zhang ◽  
Yinju Li ◽  
Chengshui Liao ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Salmonella Enterica ◽  
Caspase 3 ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Caspase 8 ◽  
Wild Type ◽  
Caspase 9 ◽  
Serovar Typhimurium ◽  
The Relationship

Abstract Background: Salmonella enterica serovar Typhimurium ( S. Typhimurium) is an important infectious disease pathogen that can survive and replicate in macrophages. Glycolysis is essential for immune responses against S. Typhimurium infection in macrophages, and is also associated with apoptosis. S. Typhimurium secreted effector K3 (SseK3) was recently identified as a novel translated and secreted protein. However, there is no study about the role of sseK3 in the relationship between apoptosis and glycolysis in cells infected with S. Typhimurium. It is unclear whether this protein exerts a significant role in the progress of apoptosis and glycolysis in S. Typhimurium-infected macrophages. Results: Macrophages were infected with S. Typhimurium SL1344 wild-type (WT), Δ sseK3 mutant or sseK3 -complemented strain, and the effects of sseK3 on apoptosis and glycolysis were determined. The adherence and invasion in the Δ sseK3 mutant group were similar to that in the WT and sseK3 -complemented groups, indicating that SseK3 was not essential for the adherence and invasion of S. Typhimurium in macrophages. However, the percentage of apoptosis in the Δ sseK3 mutant group was much lower than that in the WT and sseK3 -complemented groups. Caspase-3, caspase-8, and caspase-9 enzyme activity in the Δ sseK3 mutant group were significantly lower than in the WT group and sseK3 -complemented groups, indicating that sseK3 could improve the caspase-3, caspase-8, and caspase-9 enzyme activity. We also found that there were no significant differences in pyruvic acid levels between the three groups, but the lactic acid level in the Δ sseK3 mutant group was much lower than that in the WT and sseK3 -complemented groups. The ATP levels in the Δ sseK3 mutant group were remarkably higher than those in the WT and sseK3 -complemented groups. These indicated that the sseK3 enhanced the level of glycolysis in macrophages infected by S. Typhimurium. Conclusions: S. Typhimurium sseK3 is likely involved in promoting macrophage apoptosis and modulating glycolysis in macrophages. Our results could improve our understanding of the relationship between apoptosis and glycolysis in macrophages induced by S. Typhimurium sseK3 .

scholarly journals COPB2 gene silencing inhibits colorectal cancer cell proliferation and induces apoptosis via the JNK/c-Jun signaling pathway

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0240106
Author(s):  
Yan Wang ◽  
Guangmei Xie ◽  
Min Li ◽  
Juan Du ◽  
Min Wang
Keyword(s):  
Colorectal Cancer ◽  
Gene Silencing ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Cell Counting ◽  
Apoptosis Pathway ◽  
Proliferation And Apoptosis ◽  
Related Proteins ◽  
Hct116 Cells

Objectives Colorectal cancer (CRC) is one of the most common malignant human tumors. It is associated with high morbidity and mortality rates. In recent years, tumor gene therapy has emerged as a promising new approach for colorectal cancer therapy. Herein, we identify and analyze the role of COPB2 (coatomer protein complex, subunit beta 2) in proliferation and apoptosis of CRC cells. Methods To investigate the role of COPB2 in the proliferation and apoptosis of CRC cells, a shCOPB2 vector and a shCtrl vector were constructed for transfection into RKO and HCT116 cells. Cells proliferation was subsequently measured via cell counting kit-8 (CCK8) assay and Celigo cell counting assay. Apoptosis was measured via flow cytometry. The activity level of Caspase 3/7 was measured. Finally, the level of several JNK/c-Jun apoptosis pathway-related proteins were measured to characterize the mechanism of apoptosis. Results Our results showed that the proliferation rate was decreased and the apoptosis rate was increased in shCOPB2-treated RKO and HCT116 cells compared to those in controls. After the silencing of COPB2, JNK/c-Jun signal pathway activation was increased, the expression levels of apoptosis pathway-related proteins, such as Bad, p53 and Caspase 3, were also increased. Conclusion COPB2 gene silencing can inhibit RKO and HCT116 cells proliferation and induce apoptosis via the JNK/c-Jun signaling pathway.

scholarly journals Gut Microbiome: A Promising Biomarker for Immunotherapy in Colorectal Cancer

2019 ◽  
Vol 20 (17) ◽  
pp. 4155 ◽  
Author(s):  
Sally Temraz ◽  
Farah Nassar ◽  
Rihab Nasr ◽  
Maya Charafeddine ◽  
Deborah Mukherji ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Hematopoietic Cell Transplantation ◽  
Cytotoxic T Lymphocyte ◽  
Predictive Biomarkers ◽  
Bacterial Invasion ◽  
Host Immune System ◽  
T Cell Stimulation

Research has been driven towards finding therapy predictive biomarkers for colorectal cancer (CRC) with a special interest in studying the gut microbiome. Gut microbiome acts not only as a barrier to prevent bacterial invasion and infection, but it also affects the efficacy of hematopoietic-cell transplantation, chemotherapy, and immunotherapy. Recently, immunotherapy, which potentiates the host immune system, has revolutionized cancer therapy in general and CRC treatment specifically by increasing the quality of life and the survival of a subset of patients with this disease. In immunotherapy, the gut microbiome plays an important role in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade, programmed cell death protein 1 (PD-L1) mediation, and T cell stimulation. As such, this review will cover the role of gut microbiome in CRC, summarize approved immunotherapy treatments for CRC, and focus on the potential use of gut microbiome as a biomarker for immunotherapy.

Synergistic role of Cul1 and c-Myc: Prognostic and predictive biomarkers in colorectal cancer

2017 ◽  
Vol 38 (1) ◽  
pp. 245-252 ◽  
Author(s):  
Weimin Wang ◽  
Jianliang Deng ◽  
Qianqian Wang ◽  
Qiang Yao ◽  
Wenjiao Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Predictive Biomarkers
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