scholarly journals Promoter demethylation of nuclear factor-erythroid 2-related factor 2 gene in drug-resistant colon cancer cells

2015 ◽  
Vol 10 (3) ◽  
pp. 1287-1292 ◽  
Author(s):  
XIAO-QIAN ZHAO ◽  
YI-FEI ZHANG ◽  
YI-FANG XIA ◽  
ZHONG-MEI ZHOU ◽  
YING-QING CAO
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Related Factor ◽  
Nuclear Factor ◽  
Drug Resistant ◽  
Colon Cancer Cells

scholarly journals GLUT5 regulation by AKT1/3-miR-125b-5p downregulation induces migratory activity and drug resistance in TLR-modified colorectal cancer cells

2020 ◽  
Vol 41 (10) ◽  
pp. 1329-1340 ◽  
Author(s):  
Ga-Bin Park ◽  
Jee-Yeong Jeong ◽  
Daejin Kim
Keyword(s):  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Metabolism ◽  
Enzyme Activation ◽  
Migration And Invasion ◽  
Drug Resistant ◽  
Cancer Resistance ◽  
Colon Cancer Cells ◽  
Migratory Activity

Abstract In cancer, resistance to chemotherapy is one of the main reasons for therapeutic failure. Cells that survive after treatment with anticancer drugs undergo various changes, including in cell metabolism. In this study, we investigated the effects of AKT-mediated miR-125b-5p alteration on metabolic changes and examined how these molecules enhance migration and induce drug resistance in colon cancer cells. AKT1 and AKT3 activation in drug-resistant colon cancer cells caused aberrant downregulation of miR-125b-5p, leading to GLUT5 expression. Targeted inhibition of AKT1 and AKT3 restored miR-125b-5p expression and prevented glycolysis- and lipogenesis-related enzyme activation. In addition, restoring the level of miR-125b-5p by transfection with the mimic sequence not only significantly blocked the production of lactate and intracellular fatty acids but also suppressed the migration and invasion of chemoresistant colon cancer cells. GLUT5 silencing with small interfering RNA attenuated mesenchymal marker expression and migratory activity in drug-resistant colon cancer cells. Additionally, treatment with 2,5-anhydro-d-mannitol resensitized chemoresistant cancer cells to oxaliplatin and 5-fluorouracil. In conclusion, our findings suggest that changes in miR-125b-5p and GLUT5 expression after chemotherapy can serve as a new marker to indicate metabolic change-induced migration and drug resistance development.

scholarly journals Prooxidative Activity of Celastrol Induces Apoptosis, DNA Damage, and Cell Cycle Arrest in Drug-Resistant Human Colon Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Helena Moreira ◽  
Anna Szyjka ◽  
Kamila Paliszkiewicz ◽  
Ewa Barg
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Phase Cell ◽  
Drug Resistant ◽  
Cancer Resistance ◽  
Colon Cancer Cells ◽  
Cycle Arrest

Cancer resistance to chemotherapy is closely related to tumor heterogeneity, i.e., the existence of distinct subpopulations of cancer cells in a tumor mass. An important role is assigned to cancer stem cells (CSCs), a small subset of cancer cells with high tumorigenic potential and capacity of self-renewal and differentiation. These properties of CSCs are sustained by the ability of those cells to maintain a low intracellular reactive oxygen species (ROS) levels, via upregulation of ROS scavenging systems. However, the accumulation of ROS over a critical threshold disturbs CSCs—redox homeostasis causing severe cytotoxic consequences. In the present study, we investigated the capacity of celastrol, a natural pentacyclic triterpenoid, to induce the formation of ROS and, consequently, cell death of the colon cancer cells with acquired resistant to cytotoxic drugs (LOVO/DX cell line). LOVO/DX cells express several important stem-like cell features, including a higher frequency of side population (SP) cells, higher expression of multidrug resistant proteins, overexpression of CSC-specific cell surface marker (CD44), increased expression of DNA repair gene (PARP1), and low intracellular ROS level. We found that celastrol, at higher concentrations (above 1 μM), significantly increased ROS amount in LOVO/DX cells at both cytoplasmic and mitochondrial levels. This prooxidant activity was associated with the induction of DNA double-strand breaks (DSBs) and apoptotic/necrotic cell death, as well as with inhibition of cell proliferation by S phase cell cycle arrest. Coincubation with NAC, a ROS scavenger, completely reversed the above effects. In summary, our results provide evidence that celastrol exhibits effective cytotoxic effects via ROS-dependent mechanisms on drug-resistant colon cancer cells. These findings strongly suggest the potential of celastrol to effectively kill cancer stem-like cells, and thus, it is a promising agent to treat severe, resistant to conventional therapy, colon cancers.

scholarly journals Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis

2020 ◽  
Vol 21 (20) ◽  
pp. 7469 ◽  
Author(s):  
Jin Hong Lim ◽  
Kyung Hwa Choi ◽  
Soo Young Kim ◽  
Cheong Soo Park ◽  
Seok-Mo Kim ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Drug Effects ◽  
Control Group ◽  
Metastatic Colon Cancer ◽  
Drug Resistant ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Mouse Xenograft Model

Cancer cells can exhibit resistance to different anticancer drugs by acquiring enhanced anti-apoptotic potential, improved DNA injury resistance, diminished enzymatic inactivation, and enhanced permeability, allowing for cell survival. However, the genetic mechanisms for these effects are unknown. Therefore, in this study, we obtained drug-sensitive HT-29 cells (commercially) and drug-resistant cancer cells (derived from biochemically and histologically confirmed colon cancer patients) and performed microarray analysis to identify genetic differences. Cellular proliferation and other properties were determined after treatment with oxaliplatin, lenvatinib, or their combination. In vivo, tumor volume and other properties were examined using a mouse xenograft model. The oxaliplatin and lenvatinib cotreatment group showed more significant cell cycle arrest than the control group and groups treated with either agent alone. Oxaliplatin and lenvatinib cotreatment induced the most significant tumor shrinkage in the xenograft model. Drug-resistant and metastatic colon cancer cells evaded the anticancer drug effects via angiogenesis. These findings present a breakthrough strategy for treating drug-resistant cancer.

scholarly journals MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shaobo Bai ◽  
Yang Sun ◽  
Ying Cheng ◽  
Weiliang Ye ◽  
Chenchao Jiang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Calcium Phosphate ◽  
Protein Expression ◽  
Cancer Cells ◽  
Active Targeting ◽  
Cancer Targeting ◽  
Drug Resistant ◽  
Colon Cancer Cells ◽  
Apoptosis Pathway ◽  
Calcium Phosphate Nanoparticles

Abstract Background Colon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis. Paris saponin VII (PSVII) could not only inhibit the proliferation of colon cancer cells but also effectively induce apoptosis of drug-resistant colon cancer cells and reduce the metastasis of drug-resistant colon cancer cells as well. However, PSVII was insoluble in water and fat. It displayed no selective distribution in body and could cause severe hemolysis. Herein, colon cancer targeting calcium phosphate nanoparticles were developed to carry PSVII to treat drug-resistant colon cancer. Results PSVII carboxymethyl-β-cyclodextrin inclusion compound was successfully encapsulated in colon cancer targeting calcium phosphate nanoparticles (PSVII@MCP-CaP) by using modified citrus pectin as stabilizer agent and colon cancer cell targeting moiety. PSVII@MCP-CaP significantly reduced the hemolysis of PSVII. Moreover, by specific accumulating in orthotopic drug-resistant colon cancer tissue, PSVII@MCP-CaP markedly inhibited the growth of orthotopic drug-resistant colon cancer in nude mice. PSVII@MCP-CaP promoted the apoptosis of drug-resistant colon cancer cells through mitochondria-mediated apoptosis pathway. Moreover, PSVII@MCP-CaP significantly inhibited the invasion and migration of drug-resistant colon cancer cells by increasing E-cadherin protein expression and reducing N-cadherin and MMP-9 protein expression. Conclusion PSVII@MCP-CaP has great potential in the treatment of drug-resistant colon cancer. This study also explores a new method to prepare active targeting calcium phosphate nanoparticles loaded with a fat and water insoluble compound in water. Graphical Abstract

p65BTK targeting restores the apoptotic response to chemotherapy of p53-null drug-resistant colon cancer cells

2016 ◽  
Vol 69 ◽  
pp. S140 ◽  
Author(s):  
L. Ianzano ◽  
S. Bonomo ◽  
A. Cialdella ◽  
F. Pisano ◽  
M.G. Cerrito ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Drug Resistant ◽  
Colon Cancer Cells ◽  
Apoptotic Response ◽  
Response To Chemotherapy

scholarly journals TLR-mediated miR-125b-5p downregulation enhances CD248-induced metastasis and drug resistance in colorectal cancer cells

2019 ◽  
Author(s):  
GA-BIN PARK ◽  
Daejin Kim
Keyword(s):  
Colon Cancer ◽  
Drug Resistance ◽  
Gene Silencing ◽  
Cancer Cells ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Drug Resistant ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Migratory Activity

Abstract Background CD248, also called endosialin or tumor endothelial marker-1 (TEM1), is markedly upregulated in almost all cancers, including colon cancers. Changes in microRNA (miRNA) profiles are one of the direct causes of cancer development and progression. In this study, we investigated whether a change in CD248 expression in colon cancer cells could induce drug resistance after chemotherapy, and we explored the relationship between miR-125b-5p levels and CD248 expression in Toll-like receptor (TLR)-modified chemoresistant colon cancer cells. Methods We identified the one of the downregulated miRNAs in drug-resistant HCT8 cells using Affymetrix Genechip miRNA 4.0 array process and validated the expressional change of chemoresistant HCT-116 and HT-29 cells. Interaction between Sp1 and miR-125b-5p was confirmed by miScript target protector assay. To characterize the underlying mechanisms involved in CD248 expression, we adapted the several biological analysis techniques, including RNA-binding Protein Immunoprecipitation (RIP), migration analysis, real-Time PCR, western blot analysis, and gene silencing using siRNA. Results TLR2/6 and TLR5 upregulation in drug-resistant colon cancer cells contributed to miR-125b-5p downregulation and Sp1-mediated CD248 upregulation via NF-κB activation. Exposure to specific TLR2/6 or TLR5 ligands enhanced the expression of mesenchymal markers as well as the migratory activity of oxaliplatin (Ox)- or 5-fluorouracil (5-Fu)-resistant colon cancer cells. The transfection of a synthetic miR-125b-5p mimic into chemoresistant cells prevented Sp1 and CD248 activation and significantly impaired invasive activity. Furthermore, Sp1 or CD248 gene silencing as well as miR-125b-5p overexpression markedly reversed drug resistance and inhibited epithelial-mesenchymal transition (EMT) in colon cancer cells. Conclusions Taken together, these results suggest that changes in miR-125b-5p levels play an important role in Sp1-mediated CD248 expression and the development of drug resistance in TLR-mutated colon cancer cells.

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