scholarly journals Jacalin Has Chemopreventive Effects on Colon Cancer Development

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Thais Herrero Geraldino ◽  
Patricia Modiano ◽  
Luciana Chain Veronez ◽  
Milena Flória-Santos ◽  
Sergio Britto Garcia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Chemoprevention ◽  
Human Colon ◽  
Preneoplastic Lesions ◽  
Human Colon Cancer ◽  
Great Opportunity ◽  
Early Stages ◽  
Common Causes ◽  
Chemopreventive Activity

Colorectal cancer, which is one of the most common causes of cancer-related deaths worldwide, has a slow natural history that provides a great opportunity for prevention strategies. Plant-derived natural products have received considerable attention because of their inherent colorectal cancer chemopreventive effects. The plant lectin jacalin specifically recognizes the tumor-associated Thomsen-Friedenreich antigen and has antiproliferative effects on human colon cancer cells, highlighting its potential antitumor activity. To evaluate jacalin’s potential application in colorectal cancer chemoprevention, we studied its effects on the early stages of carcinogenesis. Balb/c mice were given 4 intrarectal deposits of 0.1 ml solution of Methyl-N′-Nitro-N-Nitroso-Guanidine (5 mg/ml) twice a week (with a 3-day interval) for 2 weeks. Starting 2 weeks before carcinogen administration, animals were treated orally with jacalin (0.5 and 25 μg) three times a week (on alternate weekdays) for 10 weeks. We show that jacalin treatment reduced the number of preneoplastic lesions in carcinogen-exposed mice. This anticarcinogenic activity was associated with decreased colonic epithelial cell proliferation and stromal COX-2 expression and with increased intestinal production of TNF-α. Our results demonstrate that jacalin is able to modulate the early stages of colon carcinogenesis and emphasize its promising chemopreventive activity in colorectal cancer.

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.

scholarly journals Animal models of gastrointestinal and liver diseases. New mouse models for studying dietary prevention of colorectal cancer

2014 ◽  
Vol 307 (3) ◽  
pp. G249-G259 ◽  
Author(s):  
James C. Fleet
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mouse Models ◽  
Human Colon ◽  
Low Grade ◽  
Preclinical Models ◽  
Dietary Interventions ◽  
Single Model ◽  
Human Colon Cancer ◽  
Molecular Etiology

Colorectal cancer is a heterogeneous disease that is one of the major causes of cancer death in the U.S. There is evidence that lifestyle factors like diet can modulate the course of this disease. Demonstrating the benefit and mechanism of action of dietary interventions against colon cancer will require studies in preclinical models. Many mouse models have been developed to study colon cancer but no single model can reflect all types of colon cancer in terms of molecular etiology. In addition, many models develop only low-grade cancers and are confounded by development of the disease outside of the colon. This review will discuss how mice can be used to model human colon cancer and it will describe a variety of new mouse models that develop colon-restricted cancer as well as more advanced phenotypes for studies of late-state disease.

Identification of polyphenol from Ziziphi spinosae semen against human colon cancer cells and colitis-associated colorectal cancer in mice

2020 ◽  
Vol 11 (9) ◽  
pp. 8259-8272
Author(s):  
Shuhua Shan ◽  
Yue Xie ◽  
Chengying Zhang ◽  
Bin Jia ◽  
Hanqing Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Pharmacological Property ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

Spinosin derived from homology of medicine and food-zizyphi spinosi semen (ZSS) exhibits a new pharmacological property against colon cancer.

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.

Sign in / Sign up

Export Citation Format

Share Document