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The Impact of Melatonin on Colon Cancer Cells' Resistance to Doxorubicin in an in Vitro Study.

ABSTRACT: Multi-drug resistance (MDR) is the main cause of low effectiveness of cancer chemotherapy. P-glycoprotein (P-gp) is one of the main factors determining MDR. Some studies indicate the potential role of melatonin (MLT) in MDR. In this study, we examined the effect of MLT on colon cancer cell's resistance to doxorubicin (DOX). Using the sulforhodamine B (SRB), method the effect of tested substances on the survival of LoVo (colon cancer cells sensitive to DOX) and LoVoDX (colon cancer cells resistant to DOX) was rated. Using immunocytochemistry (ICC), the expression of P-gp in the LoVo and LoVoDX was determined. With the real-time PCR (RT-PCR) technique, the ABCB1 expression in LoVoDX was evaluated. Based on the results, it was found that MLT in some concentrations intensified the cytotoxicity effect of DOX in the LoVoDX cells. In the ICC studies, it was demonstrated that certain concentrations of MLT and DOX cause an increase in the percentage of cells expressing P-gp, which correlates positively with ABCB1 expression (RT-PCR). The mechanism of overcoming resistance by MLT is probably not only associated with the expression of P-gp. It seems appropriate to carry out further research on the use of MLT as the substance supporting cancer chemotherapy.

SUBMITTER: Fic M

PROVIDER: S-EPMC5535889 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Impact of Andrographolide and Melatonin Combinatorial Drug Therapy on Metastatic Colon Cancer Cells and Organoids.

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| S-EPMC8182223 | biostudies-literature

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| S-EPMC7181076 | biostudies-literature

MC70 potentiates doxorubicin efficacy in colon and breast cancer in vitro treatment

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| S-ECPF-GEOD-26250 | biostudies-other

Doxorubicin resistance induces IL6 activation in the colon cancer cell line LS180.

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| S-EPMC6176352 | biostudies-literature

Promising Effect of Melatonin and Cisplatin Combination to Inhibit Cisplatin Resistance in Ovarian Cancer : an In Vitro Study

Project description: Not available

| S-BSST967 | biostudies-other

Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium-dependent activation of HIF-1alpha and P-glycoprotein overexpression.

Project description:Background and purposeArtemisinin is an antimalarial drug exerting pleiotropic effects, such as the inhibition of the transcription factor nuclear factor-kappa B and of the sarcoplasmic/endoplasmic reticulum Ca(++)-ATPase (SERCA) of P. falciparum. As the sesquiterpene lactone thapsigargin, a known inhibitor of mammalian SERCA, enhances the expression of P-glycoprotein (Pgp) by increasing the intracellular Ca(++) ([Ca(++)](i)) level, we investigated whether artemisinin and its structural homologue parthenolide could inhibit SERCA in human colon carcinoma HT29 cells and induce a resistance to doxorubicin.Experimental approachHT29 cells were incubated with artemisinin or parthenolide and assessed for SERCA activity, [Ca(++)](i) levels, Pgp expression, doxorubicin accumulation and toxicity, and translocation of the hypoxia-inducible factor, HIF-1alpha.Key resultsArtemisinin and parthenolide, like the specific SERCA inhibitors thapsigargin and cyclopiazonic acid, reduced the activity of SERCA. They also increased intracellular calcium concentration ([Ca(++)](i)) and Pgp expression and decreased doxorubicin accumulation and cytotoxicity. The intracellular Ca(++) chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, and the inhibitor of calmodulin-dependent kinase II (CaMKII) KN93 prevented these effects. CaMKII is known to promote the phosphorylation and the activation of HIF-1alpha, which may induce Pgp. In HT29 cells, artemisinin and parthenolide induced the phosphorylation of HIF-1alpha, which was inhibited by KN93.Conclusions and implicationsOur results suggest that artemisinin and parthenolide may act as SERCA inhibitors and, like other SERCA inhibitors, induce resistance to doxorubicin in human colon cancer cells, via the CaMKII-dependent activation of HIF-1alpha and the induction of Pgp.

| S-EPMC2697684 | biostudies-literature

MC70 potentiates doxorubicin efficacy in colon and breast cancer in vitro treatment

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2010-12-22 | GSE26250 | GEO

Aldose reductase inhibitor increases doxorubicin-sensitivity of colon cancer cells and decreases cardiotoxicity.

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MC70 potentiates doxorubicin efficacy in colon and breast cancer in vitro treatment

2010-12-22 | E-GEOD-26250 | biostudies-arrayexpress

Nitric oxide donor doxorubicins accumulate into Doxorubicin-resistant human colon cancer cells inducing cytotoxicity.

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