scholarly journals Myotubularin-Related Phosphatase 3 Promotes Growth of Colorectal Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Bo’an Zheng ◽  
Xiaojun Yu ◽  
Rui Chai
Keyword(s):  
Colorectal Cancer ◽  
Flow Cytometry ◽  
Cell Growth ◽  
Cell Apoptosis ◽  
Intracellular Signaling ◽  
Dietary Habits ◽  
Annexin V ◽  
Human Colon ◽  
Phase Cell ◽  
Human Colon Cancer

Due to changes in lifestyle, particularly changes in dietary habits, colorectal cancer (CRC) increased in recent years despite advances in treatment. Nearly one million new cases diagnosed worldwide and half a million deaths make CRC a leading cause of cancer mortality. In the present study, we aimed to investigate the role of myotubularin-related phosphatase 3 (MTMR3) in CRC cell growth via lentivirus-mediated small interfering RNA (siRNA) transduction in human colon cancer cell lines HCT116 and SW1116. The effect of MTMR3 knockdown on cell growth was evaluated by MTT, colony formation, and flow cytometry assays. The effect of MTMR3 knockdown on cell apoptosis was evaluated by flow cytometry with Annexin V/7-AAD double staining. The activation of apoptotic markers, Bad and PARP, was detected using Intracellular Signaling Array. Knockdown of MTMR3 resulted in a significant reduction in cell proliferation in both HCT116 and SW1116 cells. Moreover, knockdown of MTMR3 led to S phase cell cycle arrest. Furthermore, knockdown of MTMR3 induced cell apoptosis via phosphorylation of Bad and cleavage of PARP. These results indicate that MTMR3 may play an important role in the progression of CRC and suggest that siRNA mediated silencing of MTMR3 could be an effective tool in CRC treatment.

Studies on Apoptosis and Mechanism of Curcumin Chitosan Induced Human Colon Cancer Cells in Colorectal Cancer

2020 ◽  
Vol 10 (7) ◽  
pp. 987-991
Author(s):  
Quanlan Wang ◽  
Peng Liao ◽  
Yinglin Wu ◽  
Yuanhua Huang ◽  
Yan Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Flow Cytometry ◽  
Annexin V ◽  
Human Colon ◽  
Optical Microscope ◽  
Inhibitory Effect ◽  
Control Group ◽  
Dependent Manner ◽  
Human Colon Cancer ◽  
Ht29 Cells

To explore the function of curcumin chitosan on the proliferation of human colorectal cancer HT29 cells and to explore its effect on apoptosis. We applied MTT assay to test the inhibitory effect of curcumin chitosan on the proliferation of HT29 cells. The alterations of colorectal cancer cell morphology were observed by optical microscope and electron microscope. The change of early apoptosis rate was determined by flow cytometry using Annexin-V/PI double staining. By Comparison with the control group, curcumin chitosan significantly suppressed the cell proliferation and promoted cell apoptosis of HT29 cells in not only dose- but also time-dependent manner; through light microscopy and electron microscopy, the cell volume was reduced, the cell membrane was shrunk, chromatin was significantly concentrated. Typical apoptotic features such as aggregation; flow cytometry confirmed a significant increase in apoptotic rates (p < 0 05).

scholarly journals New CXCR4 Antagonist Peptide R (Pep R) Improves Standard Therapy in Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1952
Author(s):  
Crescenzo D’Alterio ◽  
Antonella Zannetti ◽  
Anna Maria Trotta ◽  
Caterina Ieranò ◽  
Maria Napolitano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Growth ◽  
Standard Therapy ◽  
Hct116 Cell ◽  
Human Colon ◽  
Chemotherapeutic Agents ◽  
Cxcr4 Antagonist ◽  
Human Colon Cancer

The chemokine receptor CXCR4 is overexpressed and functional in colorectal cancer. To investigate the role of CXCR4 antagonism in potentiating colon cancer standard therapy, the new peptide CXCR4 antagonist Peptide R (Pep R) was employed. Human colon cancer HCT116 xenograft-bearing mice were treated with chemotherapeutic agents (CT) 5-Fluorouracil (5FU) and oxaliplatin (OX) or 5FU and radio chemotherapy (RT-CT) in the presence of Pep R. After two weeks, CT plus Pep R reduced by 4-fold the relative tumor volume (RTV) as compared to 2- and 1.6-fold reductions induced, respectively, by CT and Pep R. In vitro Pep R addition to CT/RT-CT impaired HCT116 cell growth and further reduced HCT116 and HT29 clonal capability. Thus, the hypothesis that Pep R could target the epithelial mesenchyme transition (EMT) process was evaluated. While CT decreased ECAD and increased ZEB-1 and CD90 expression, the addition of Pep R restored the pretreatment expression. In HCT116 and HT29 cells, CT/RT-CT induced a population of CD133+CXCR4+ cells, supposedly a stem-resistant cancer cell population, while Pep R reduced it. Taken together, the results showed that targeting CXCR4 ameliorates the effect of treatment in colon cancer through inhibition of cell growth and reversal of EMT treatment-induced markers, supporting further clinical studies.

scholarly journals Enhancement of Annexin V in response to combination of epigallocatechin gallate and quercetin as a potent arrest the cell cycle of colorectal cancer

2023 ◽  
Vol 83 ◽  
Author(s):  
Maryam A. Al-Ghamdi ◽  
A. AL-Enazy ◽  
E.A Huwait ◽  
A. Albukhari ◽  
S. Harakeh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Epigallocatechin Gallate ◽  
Annexin V ◽  
Antitumor Agent ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Cycle Arrest ◽  
Hct 116 ◽  
Conventional Chemotherapeutic Agent

Abstract Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.

scholarly journals Ivermectin has New Application in Inhibiting Colorectal Cancer Cell Growth

2021 ◽  
Vol 12 ◽  
Author(s):  
Shican Zhou ◽  
Hang Wu ◽  
Wenjuan Ning ◽  
Xiao Wu ◽  
Xiaoxiao Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Annexin V ◽  
Optical Microscope ◽  
Dependent Manner ◽  
Mechanism Analysis ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Colorectal cancer (CRC) is the third most common cancer worldwide and still lacks effective therapy. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. However, whether ivermectin affects CRC is still unclear. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. We used CCK-8 assay to determine the cell viability, used an optical microscope to measure cell morphology, used Annexin V-FITC/7-AAD kit to determine cell apoptosis, used Caspase 3/7 Activity Apoptosis Assay Kit to evaluate Caspase 3/7 activity, used Western blot to determine apoptosis-associated protein expression, and used flow cytometry and fluorescence microscope to determine the reactive oxygen species (ROS) levels and cell cycle. The results demonstrated that ivermectin dose-dependently inhibited colorectal cancer SW480 and SW1116 cell growth, followed by promoting cell apoptosis and increasing Caspase-3/7 activity. Besides, ivermectin upregulated the expression of proapoptotic proteins Bax and cleaved PARP and downregulated antiapoptotic protein Bcl-2. Mechanism analysis showed that ivermectin promoted both total and mitochondrial ROS production in a dose-dependent manner, which could be eliminated by administering N-acetyl-l-cysteine (NAC) in CRC cells. Following NAC treatment, the inhibition of cell growth induced by ivermectin was reversed. Finally, ivermectin at low doses (2.5 and 5 µM) induced CRC cell arrest. Overall, ivermectin suppressed cell proliferation by promoting ROS-mediated mitochondrial apoptosis pathway and inducing S phase arrest in CRC cells, suggesting that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers.

scholarly journals RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3192
Author(s):  
Antoine Gleizes ◽  
Mouna Triki ◽  
Sandrine Bonnet ◽  
Naomi Baccari ◽  
Gabriel Jimenez-Dominguez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Differentiation ◽  
Paneth Cell ◽  
Wnt Signaling Pathway ◽  
Cell Lineage ◽  
Human Colon ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Sox9 Expression ◽  
Human Colon Cancer

RIP140 is a major transcriptional coregulator of gut homeostasis and tumorigenesis through the regulation of Wnt/APC signaling. Here, we investigated the effect of RIP140 on Paneth cell differentiation and its interplay with the transcription factor SOX9. Using loss of function mouse models, human colon cancer cells, and tumor microarray data sets we evaluated the role of RIP140 in SOX9 expression and activity using RT-qPCR, immunohistochemistry, luciferase reporter assays, and GST-pull down. We first evidence that RIP140 strongly represses the Paneth cell lineage in the intestinal epithelium cells by inhibiting Sox9 expression. We then demonstrate that RIP140 interacts with SOX9 and inhibits its transcriptional activity. Our results reveal that the Wnt signaling pathway exerts an opposite regulation on SOX9 and RIP140. Finally, the levels of expression of RIP140 and SOX9 exhibit a reverse response and prognosis value in human colorectal cancer biopsies. This work highlights an intimate transcriptional cross-talk between RIP140 and SOX9 in intestinal physiopathology.

scholarly journals Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helena de Castro e Gloria ◽  
Laura Jesuíno Nogueira ◽  
Patrícia Bencke Grudzinski ◽  
Paola Victória da Costa Ghignatti ◽  
Temenouga Nikolova Guecheva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Mismatch Repair ◽  
Cell Cycle Progression ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Human Colon ◽  
Human Colon Cancer

Abstract Background The advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved. Methods Human colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed. Results Our results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities. Conclusion Our results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.

PEGylated Active Carbon Nanoparticles with Improved Dispersivity in Water and Potential Application in Lymphatic Targeted Therapy of Colorectal Cancer

2021 ◽  
Vol 66 ◽  
pp. 85-102
Author(s):  
Wen Kai Liu ◽  
Yuan Qing Song ◽  
Yan Ma ◽  
Xin Li ◽  
Peng Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Active Carbon ◽  
Potential Application ◽  
Carbon Nanoparticles ◽  
Drug Loading ◽  
Human Colon ◽  
Tumor Treatment ◽  
Human Colon Cancer ◽  
Pegylated Nanoparticles ◽  
Improved Stability

A series of PEGylated active carbon nanoparticles were fabricated with improved dispersity in water and were explored for their ability for carrying drugs and potential application in lymphatic targeted tracing and chemotherapy of colorectal cancer. The active carbon nanoparticles were oxidized in a mild condition with 30% H2O2 solution and then mPEG-NH2 was grafted to the nanoparticles. Compared with the original carbon nanoparticles, the oxidized and PEGylated nanoparticles all present improved stability and initial solubility in water and the PEGylated nanoparticles perform best. Size of the nanoparticles was well controlled in a rational area which can fulfill the requirement for lymphatic targeting. The PEGylated nanoparticles have excellent drug loading properties and allow for sustained release under physiological conditions. The MTT results show the drug-loaded nanoparticles can effectively kill SW480 cells (Human Colon Cancer Cells). These characteristics make the PEGylated nanoparticles become a promising candidate for using as drug-loaded powder for both lymphatic targeted tracing and chemo-therapy without using suspending agent in tumor treatment.

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