Amitriptyline may have a supportive role in cancer treatment by inhibiting glutathione S-transferase pi (GST-π) and alpha (GST-α)

Kulaksiz-Erkmen, Gulnihal; Dalmızrak, Özlem; Dincsoy-Tuna, Gamze; Doğan, Arın; Öğüş, I. Hamdi; Özer, Nazmi

doi:10.3109/14756366.2011.639017

Cited by 21 publications

(13 citation statements)

References 31 publications

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“…Interestingly, covalent inhibitors showed prolonged inactivation of GST enzymes and hold promise for use as antineoplastic agents against GSTP1-overexpressing tumors. Additionally, amitriptyline, a commonly prescribed drug for clinical depression, significantly inhibits the activity of GSTP1 and GSTA1 by binding to their G-sites; however, the binding of amitriptyline to the GST proteins is reversible [ 179 ].…”

Section: Gst Inhibitors and Their Therapeutic Implicationsmentioning

confidence: 99%

Glutathione S-Transferases in Cancer

2021

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In humans, the glutathione S-transferases (GST) protein family is composed of seven members that present remarkable structural similarity and some degree of overlapping functionalities. GST proteins are crucial antioxidant enzymes that regulate stress-induced signaling pathways. Interestingly, overactive GST proteins are a frequent feature of many human cancers. Recent evidence has revealed that the biology of most GST proteins is complex and multifaceted and that these proteins actively participate in tumorigenic processes such as cell survival, cell proliferation, and drug resistance. Structural and pharmacological studies have identified various GST inhibitors, and these molecules have progressed to clinical trials for the treatment of cancer and other diseases. In this review, we discuss recent findings in GST protein biology and their roles in cancer development, their contribution in chemoresistance, and the development of GST inhibitors for cancer treatment.

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Section: Gst Inhibitors and Their Therapeutic Implicationsmentioning

confidence: 99%

Glutathione S-Transferases in Cancer

2021

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“…GST- π is a second-phase metabolic enzyme that is highly expressed in many human cancers. It binds to GSH (glutathione) and is secreted by multidrug resistance-related proteins to reduce the cytotoxicity of chemotherapy drugs [ 18 ]. MRPs recognize chemotherapeutic drugs to which they couple to reduce intracellular drug concentrations thus promoting resistance [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Curcumin Regulates ERCC1 Expression and Enhances Oxaliplatin Sensitivity in Resistant Colorectal Cancer Cells through Its Effects on miR‐409‐3p

Han

Yin

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Oxaliplatin (L-OHP) resistance is a major obstacle to the effective treatment of colorectal cancer. The resistance mechanism(s) of colorectal tumors to L-OHP may be related to the regulation of ERCC1 by cancer-expressed miRNAs, but no in-depth studies on the miRNAs that affect drug resistance have been performed. Curcumin (Cur) can reverse the drug resistance of cancer cells, but its effects on ERCC1 expression and miRNA profiles in colorectal cancer have not been studied. Methods. To study the regulation effect of curcumin on ERCC1 expression and its effects on miRNAs, the L-OHP-resistant colorectal cancer cell line HCT116/L-OHP was established. MTT assays were used to evaluate cell proliferation. Flow cytometry was used to investigate apoptotic induction. Western blot and RT-PCR analysis were used to evaluate the expression of drug-associated ERCC1, Bcl-2, GST-π, MRP, P-gp, and survivin. Results. HCT116//L-OHP cell lines were successfully established. The combination of L-OHP and curcumin could reduce L-OHP resistance in vitro. In addition, combination therapy inhibited the expression of ERCC1, Bcl-2, GST-π, MRP, P-gp, and survivin at the mRNA and protein level. Curcumin was found to inhibit ERCC1 through its ability to modulate miR-409-3p. Conclusion. Curcumin can overcome L-OHP resistance in colorectal cancer cells through its effects on miR-409-3p mediated ERCC1 expression.

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“…The genes associated with MDR include MDR1/P-gp [29,30], MRP-1 [31,32], GST-π [33,34], Bcl-2 [35], TS [36,37] and Bax [38], before and after the intervention of ZNF139 in GC cells to delineate the regulating mechanism of ZNF139- miR-185 pathway in GC MDR. In addition, it was demonstrated that the inhibition of ZNF139 attenuated expression of MDR1/P-gp, MRP and Bcl-2, while levels of their expression were increased dramatically after transfection of miR-185 mimic.…”

Section: Discussionmentioning

confidence: 99%

ZNF139 increases multidrug resistance in gastric cancer cells by inhibiting miR-185

et al. 2018

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It has been reported that the expression of zinc finger protein 139 (ZNF139) and microRNA-185 (miR-185) were associated with proliferation, drug resistance of gastric cancer (GC) cells. However, the detailed mechanisms have not been fully investigated. The expression of ZNF139 in both GC tissues and cell lines was tested, then SGC7901/ADR or SGC7901 cells were transfected with ZNF139-siRNA, miR-185 analog, or pcDNA-ZNF139. Cell activity was determined by MTT assay. Real-time PCR and Western blot were utilized to detect ZNF139, miR-185, and multidrug resistance (MDR) related genes including MDR1/P-gp, GST-π, MRP-1, Bcl-2, TS and Bax. ChIP and dual luciferase activity assay were used to investigate regulation between ZNF139 and miR-185. Increased ZNF139 and decreased miR-185 expression were detected in GC tissues and cell lines. Transfection with ZNF139-siRNA into SGC7901/ADR cells markedly increased expression of miR-185, and treating with chemotherapeutic drugs ADR, 5-FU, L-OHP, the survival rate of SGC7901/ADR cells obviously decreased after ZNF139-siRNA transfection. On the other hand, transfection with pcDNA-ZNF139 in GC cell line SGC7901 resulted in an increased expression level of ZNF139 and a decline in the expression level of miR-185, meanwhile drug resistance of GC cells was clearly enhanced to ADR, 5-FU, L-OHP. Dual luciferase activity assay demonstrated that ZNF139 inhibited transcriptional activities of miR-185’s promoter in cells transfected with the reporter plasmid encompassing the upstream promoter region of miR-185 along with pcDNA-ZNF139. Our data reveal that ZNF139 might promote MDR gene MDR1/P-gp, MRP-1 and Bcl-2 by prohibiting miR-185.

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Amitriptyline may have a supportive role in cancer treatment by inhibiting glutathione S-transferase pi (GST-π) and alpha (GST-α)

Cited by 21 publications

References 31 publications

Glutathione S-Transferases in Cancer

Glutathione S-Transferases in Cancer

Curcumin Regulates ERCC1 Expression and Enhances Oxaliplatin Sensitivity in Resistant Colorectal Cancer Cells through Its Effects on miR‐409‐3p

ZNF139 increases multidrug resistance in gastric cancer cells by inhibiting miR-185

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