Pharmacodynamic mechanisms of anti-inflammatory drugs on the chemosensitization of multidrug-resistant cancers and the pharmacogenetics effectiveness

Dehkordi, Neda Gholamian; Mirzaei, Seyed Abbas; Elahian, Fatemeh

doi:10.1007/s10787-020-00765-9

Cited by 10 publications

(7 citation statements)

References 128 publications

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“…The regulatory relationship between NF-κB and MDR1 has been the subject of several studies [17][18][19] . Ogretmen et al demonstrated that a protein complex composed of NF-κB /p65 and c-Fos transcription factors interacts with the CAAT promoter region in MCF7 cells to negatively regulate human mdr1 promoter activity.…”

Section: Discussionmentioning

confidence: 99%

Comparison of effects of aminosalicylic acid, glucocorticoids and immunosuppressive agents on the expression of multidrug-resistant genes in ulcerative colitis

Chen

Wang

Zhang

et al. 2022

Sci Rep

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To compare the effects of aminosalicylic acid, glucocorticoids and immunosuppressants on the expression levels of multidrug resistance genes in patients with ulcerative colitis (UC), with the aim of providing a theoretical and therapeutic basis for the diagnosis, treatment, and prevention of UC. Fresh colonic mucosal tissues or postoperative pathological biopsies from 148 UC patients were collected, and the distribution sites and morphology of P-glycoprotein (P-gp) were detected using immunohistochemical staining. RT-PCR was used to quantify the expression levels of multidrug resistance gene (MDR1) mRNA before and after the corresponding treatment, and the effects of aminosalicylic acid, glucocorticoids and immunosuppressive drugs on P-gp were compared. In addition, the effects of the three drugs on MDR1 mRNA were analyzed. Administration of 5-aminosalicylic acid (5-ASA) drugs did not correlate with MDR1 expression in UC, whereas administration of glucocorticoids and immunosuppressive drugs was positively correlated with MDR1 expression profile. The expression levels of MDR1 mRNA and its product P-gp were significantly upregulated in patients who did not respond to glucocorticoids and immunosuppressive drugs. 5-ASA had no effect on the expression levels of MDR1 and its product P-gp in patients with a confirmed diagnosis of UC. However, the use of glucocorticoids and immunosuppressants can increase the expression level of MDR1.

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Section: Discussionmentioning

confidence: 99%

Comparison of effects of aminosalicylic acid, glucocorticoids and immunosuppressive agents on the expression of multidrug-resistant genes in ulcerative colitis

Chen

Wang

Zhang

et al. 2022

Sci Rep

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“…Pharmacogenetic studies have demonstrated that genetic variation is one of the leading causes of variability in drug response. Among different types of genetic variations that affect inter-individual drug response, single nucleotide polymorphisms (SNPs) play a critical role due to their occurrence frequency of >1% in the human population ( Gholamian Dehkordi et al, 2021 ). Because different NSAIDs have various molecular targets, including the most classical COX enzymes and COX-independent molecules, genetic variations in these genes and their closely related upstream or downstream genes can be tremendous.…”

Section: Drug Metabolism Anti-cancer Mechanisms and Pharmacogenomics ...mentioning

confidence: 99%

Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics

Lai

Liu

et al. 2022

Front. Pharmacol.

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Inflammatory processes are essential for innate immunity and contribute to carcinogenesis in various malignancies, such as colorectal cancer, esophageal cancer and lung cancer. Pharmacotherapies targeting inflammation have the potential to reduce the risk of carcinogenesis and improve therapeutic efficacy of existing anti-cancer treatment. Non-steroidal anti-inflammatory drugs (NSAIDs), comprising a variety of structurally different chemicals that can inhibit cyclooxygenase (COX) enzymes and other COX-independent pathways, are originally used to treat inflammatory diseases, but their preventive and therapeutic potential for cancers have also attracted researchers’ attention. Pharmacogenomic variability, including distinct genetic characteristics among different patients, can significantly affect pharmacokinetics and effectiveness of NSAIDs, which might determine the preventive or therapeutic success for cancer patients. Hence, a more comprehensive understanding in pharmacogenomic characteristics of NSAIDs and cancer-related inflammation would provide new insights into this appealing strategy. In this review, the up-to-date advances in clinical and experimental researches targeting cancer-related inflammation with NSAIDs are presented, and the potential of pharmacogenomics are discussed as well.

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“…ATP‐binding cassette transporters such as ABCB1 (P‐glycoprotein) and ABCG2 breast cancer resistance protein (BCRP) pharmacokinetic genes are expressed in normal tissues having barrier functions, such as in the liver, kidney, intestine and blood‐brain barrier (BBB) endothelial cells. They act as an ATP‐dependent efflux pump to reduce the level of intracellular drugs to below the cytotoxicity threshold (Bukowski et al, 2020; Gholamian Dehkordi et al, 2021; Pan et al, 2016; Qin et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

“…as an ATP-dependent efflux pump to reduce the level of intracellular drugs to below the cytotoxicity threshold (Bukowski et al, 2020;Gholamian Dehkordi et al, 2021;Pan et al, 2016;Qin et al, 2023).…”

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confidence: 99%

Paynantheine more effectively reverses multidrug resistance in malignant EPG85.257RDB and MCF7MX cells than morphine and speciociliatine

Abdali,

Nadipour Borujeni,

Hosseini

et al. 2024

Cell Biology International

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The possible interactions of morphine, paynantheine and speciociliatine alkaloids with ATP‐binding cassette (ABC) transporters was investigated. The compounds were docked against ABCG2 and ABCB1 to predict the binding mode of alkaloids in active binding sites. The cytotoxicity of morphine, paynantheine and speciociliatine for EPG85.257RDB and MCF7MX cells was determined and ABCB1 and ABCG2 gene and protein expression were determined. The binding score of paynantheine to ABCB1 was higher in the docking studies. Paynantheine and speciociliatine had similar binding scores to ABCB1, but higher binding scores to ABCG2 than did morphine. Paynantheine and speciociliatine were more effective against MCF7MX and EPG85.257RDB cells and showed greater cyctotoxicity in the MTT assay. The effect of morphine and paynantheine on the ABCB1 gene and protein expression suggests these compounds can reduce resistance in cancer patients, but that speciociliatine may not be a suitable candidate because of its increased ABCB1 expression while speciociliatine decreased the expression of ABCG2 in MCF7MX cells. This indicates that speciociliatine is a better candidate for reducing drug resistance in this cell line. Structural modification, drug‐metabolizing enzymes and differences in the binding sites could cause functional differences between these compounds.

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Pharmacodynamic mechanisms of anti-inflammatory drugs on the chemosensitization of multidrug-resistant cancers and the pharmacogenetics effectiveness

Cited by 10 publications

References 128 publications

Comparison of effects of aminosalicylic acid, glucocorticoids and immunosuppressive agents on the expression of multidrug-resistant genes in ulcerative colitis

Comparison of effects of aminosalicylic acid, glucocorticoids and immunosuppressive agents on the expression of multidrug-resistant genes in ulcerative colitis

Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics

Paynantheine more effectively reverses multidrug resistance in malignant EPG85.257RDB and MCF7MX cells than morphine and speciociliatine

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