Synergistic anticancer properties of docosahexaenoic acid and 5-fluorouracil through interference with energy metabolism and cell cycle arrest in human gastric cancer cell line AGS cells

Gao, Kun; Liang, Qi; Zhao, Zhihao; Li, You-Fen; Wang, Shufeng

doi:10.3748/wjg.v22.i10.2971

Cited by 27 publications

(21 citation statements)

References 34 publications

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“…ABCC1 can confer resistance to many commonly used anticancer drugs, including 5-fluorouracil [16,17]. 5-FU, was the first synthetic analog of the pyrimidine base uracil which showed pharmacological activity [18][19][20][21]. At the molecular level, 5-FU is an antineoplastic antimetabolite that interferes with DNA synthesis by blocking the thymidylate synthase-catalyzed conversion of deoxyuridylic acid to thymidylic acid [18].…”

Section: Introductionmentioning

confidence: 99%

“…At the molecular level, 5-FU is an antineoplastic antimetabolite that interferes with DNA synthesis by blocking the thymidylate synthase-catalyzed conversion of deoxyuridylic acid to thymidylic acid [18]. In the in vitro studies 5-FU was shown to induce apoptosis and cell cycle arrest and inhibit proliferation in numerous cancer cell lines [19][20][21]. Since 1957 5-FU has been a widely administered anticancer drug and it still plays an important role in the treatment of several cancers, including colon and breast cancers [22].…”

Section: Introductionmentioning

confidence: 99%

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New uracil analogs as downregulators of ABC transporters in 5-fluorouracil-resistant human leukemia HL-60 cell line

et al. 2019

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Overexpression of ATP-binding cassette (ABC) transporters causing multidrug resistance (MDR) in cancer cells is one of the major obstacles in cancer chemotherapy. The 5-FU resistant subclone (HL-60/5FU) of the human HL-60 promyelocytic leukemia cell line was selected by the conventional method of continuous exposure of the cells to the drug up to 0.08 mmol/L concentration. HL-60/5FU cells exhibited six-fold enhanced resistance to 5-FU than HL-60 cells. RT-PCR and ELISA assay showed significant overexpression of MDR-related ABC transporters, ABCB1, ABCG2 but especially ABCC1 in the HL-60/5FU as compared with the parental cell line. Three novel synthetic 5-methylidenedihydrouracil analogs, U-236, U-332 and U-359, selected as highly cytotoxic for HL-60 cells in MTT test, showed similar cytotoxicity in the resistant cell line. When co-incubated with 5-FU, these analogs were found to down-regulate the expression of all three transporters. However, the most pronounced effect was caused by U-332 which almost completely abolished ABCC1 expression in the resistant HL-60/5FU cells. Additionally, U-332 inhibited the activity of ATPase, an enzyme which catalyzes hydrolysis of ATP, providing energy to efflux drugs from the cells through the cellular membranes. Taken together, the obtained data suggest that acquired 5-FU resistance in HL-60/5FU cells results from overexpression of ABCC1 and that targeting ABCC1 expression could be a potential approach to re-sensitize resistant leukemia cells to 5-FU. The synthetic uracil analog U-332, which can potently down-regulate ABC transporter expression and therefore disturb drug efflux, can be considered an efficient ABCC1 regulator in cancer cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New uracil analogs as downregulators of ABC transporters in 5-fluorouracil-resistant human leukemia HL-60 cell line

et al. 2019

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“…Gao et al [27] reported the significant downregulation of the expression of mitochondrial electron transfer change complexes. Siddiqui et al [28] reported an important role of cyclooxygenase-2, NF-κB, peroxisome proliferator-activated receptor gamma, mitogen-activated protein kinese.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Eicosapentaenoic Acid on Antiproliferative Action of Anticancer Drugs in a Cancer Cell Line Model

et al. 2017

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Background/Aims: It has been found experimentally and clinically that eicosapentaenoic acid (EPA) exerts an anticancer effect and that it has a minimal adverse event profile relative to other anticancer drugs. Any synergy between EPA and other anticancer drugs could be of therapeutic relevance, especially in elderly or high-risk patients. Therefore, we investigated the synergism between anticancer drugs and EPA experimentally. Methods: EPA was coadministered in vitro with various anticancer drugs (paclitaxel, docetaxel, 5-fluorouracil and cis-diamminedichloridoplatinum[II]) to TE-1 cells, which were derived from human esophageal cancer tumors. Cell proliferation was measured by the water soluble tetrazolium-1 method. Result: Sub-threshold concentrations of EPA, which alone produced no anticancer effect, caused a synergistic suppressive effect on TE-1 cell proliferation when combined with other anticancer agents. Conclusion: Coadministration of EPA with other anticancer drugs may represent a new therapeutic paradigm offering a reduced side effect profile.

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“…Cells (2x10 4 cells/well) in 96-well plates were exposed to various concentrations of Ox or 5-Fu for 24 h. The inhibition rate of cell growth was measured using the following formula: inhibition rate (%) = [1 -OD 570 (experiment group)/OD 570 (control group)] × 100 [23]. Cytotoxicity curves were obtained using GraphPad software by plotting the measured cell viability (%) indicated by Cell Counting Kit-8…”

Section: Cytotoxicity Assay For Ic 50 Determination and Establishmentmentioning

confidence: 99%

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

PARK

Kim

2019

Preprint

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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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Synergistic anticancer properties of docosahexaenoic acid and 5-fluorouracil through interference with energy metabolism and cell cycle arrest in human gastric cancer cell line AGS cells

Abstract: Synergistic anticancer properties of DHA and 5-FU may involve interference with energy production of AGS cells via downregulation of METCs and cell cycle arrest.

Cited by 27 publications

References 34 publications

New uracil analogs as downregulators of ABC transporters in 5-fluorouracil-resistant human leukemia HL-60 cell line

New uracil analogs as downregulators of ABC transporters in 5-fluorouracil-resistant human leukemia HL-60 cell line

Synergistic Effect of Eicosapentaenoic Acid on Antiproliferative Action of Anticancer Drugs in a Cancer Cell Line Model

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

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