Curcumin Reverses 5-Fluorouracil Resistance by Promoting Human Colon Cancer HCT-8/5-FU Cell Apoptosis and Down-regulating Heat Shock Protein 27 and P-Glycoprotein

Exploring the mechanism through which berberine (Ber) reverses the multidrug resistance (MDR) of breast cancer is of great importance. Herein, we used the methyl thiazolyl tetrazolium assay to determine the drug resistance and cytotoxicity of Ber and doxorubicin (DOX) alone or in combination on the breast cancer cell line MCF-7/DOX Fluc . The results showed that Ber could synergistically enhance the inhibitory effect of DOX on tumor cell proliferation in vitro , and the optimal combination ratio was Ber/DOX = 2:1. Using a luciferase reporter assay system combined with the bioluminescence imaging technology, the efflux kinetics of d -luciferin potassium salt in MCF-7/DOX Fluc cells treated with Ber in vivo was investigated. The results showed that Ber could significantly reduce the efflux of d -luciferin potassium salt in MCF-7/DOX Fluc cells. In addition, western blot and immunohistochemistry experiments showed that the expression of P-glycoprotein (P-gp/ABCB1) and multidrug resistance protein 1 (MRP1/ABCC1) in MCF-7/DOX Fluc cells was downregulated upon Ber treatment. Finally, high-performance liquid chromatography was used to investigate the effect of Ber on DOX tissue distribution in vivo , and the results showed that the uptake of DOX in tumor tissues increased significantly when combined with Ber ( P < 0.05). Thus, the results illustrated that Ber can reverse MDR by inhibiting the efflux function of ATP-binding cassette transporters and downregulating their expression levels.

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“…TCM can act on multiple components of interest at once, which is likely key to reversing MDR. 14 − 17 …”

Section: Introductionmentioning

confidence: 99%

Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo

et al. 2021

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“…Colorectal cancer is the third deadliest cancer in the world and many people die every year in the world due to this diease. Chemotherapy takes an important place among colon cancer treatment options and 5-FU is widely used as a chemotherapeutic agent [15]. In the treatment of colorectal cancer, it is important to develop drug combinations that will increase the effectiveness of chemotherapy and to determine the molecular targets of the drugs [16].…”

Section: Discussionmentioning

confidence: 99%

The Role of SIRT5 and p53 Proteins in the Sensitivity of Colon Cancer Cells to Chemotherapeutic Agent 5-Fluorouracil 

Ekremoglu

Koç

2021

Preprint

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In the treatment of colorectal cancer, it is important to develop drug combinations that will increase the effectiveness of chemotherapy and to determine the molecular targets of the drugs. Therefore, combined therapies that can increase the sensitivity of 5-Fluourouracil (5-FU), a chemotherapeutic agent used in the treatment of colon cancer, and also the molecular pathways involved in this process are important in the treatment of the disease. Here we examined the SIRT5 (Resveratrol and Suramin) and p53 (Nutlin3a) modulators alone or in combination with 5-FU on the proliferation of colon cancer cells and effect of 5-FU on the SIRT5 and FOXO3a expressions whether p53 dependent or independent manner. p53 protein expression is activated by nutlin3a in HCT-116 p53 +/+ cells and HCT-116 p53 -/- cells were used as counterpart cells that did not express p53. According to our MTT assay results, we showed that these modulators have significant effects on the sensitivity of both cells to 5-FU. In p53+/+ cells, Resveratrol (RSV) and Nutlin3a and in p53 -/- cells, Suramin was found to be more effective. These differences were evaluated together with the effect of 5-FU on the SIRT5-FOXO3a-Bim axis in p53 +/+ and p53 -/- cells. SIRT5 is known to deactivate FOXO3a which plays a role in the induction of apoptosis via Bim. Our western blot experiment results showed that while Suramin decreased SIRT5 and RSV decreased FOXO3a protein expressions significantly in HCT-116 p53 -/- cells, 5-FU decreased significantly SIRT5 and FOXO3a protein expressions p53 independently. These results may help the discovery of new markers in colon cancer treatment.

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“…For instance, the toxicity profile was alleviated when the co-treatment of 5 μM curcumin lowered the concentration of 5-FU (0.01 nM; originally 10 nM) required in diminishing the cell proliferation of 3D cell culture models [ 77 ]. Concurrently, this was associated with G0/G1 cell cycle arrest via cyclin D1 inactivation [ 78 , 79 ]. Another cell cycle study showed that the co-treatment of curcumin and 5-FU caused S phase arrest in 5-FU-resistant HCT116 cell lines, implying that the regulation of cell cycle is cell-specific [ 80 ].…”

Section: Curcumin Combination Anticancer Therapy In Preclinical Studiesmentioning

confidence: 99%

“…Furthermore, invasion assays revealed that this treatment combination reduced the migratory behaviour of colorectal cancer cells via the inhibition of MMP-9 and C-X-C chemokine receptor type 4 (CXCR4) expression, the downregulation of NF-κB expression, and disruption of ten–eleven translocation methylcytosine dioxygenase 1 (TET1)–naked cuticle homolog 2 (NKD2)–Wnt signalling pathways [ 77 , 79 ]. Apart from that, they also promoted the apoptotic activities in colon cancer cells via the upregulation of Bax and the cleavage of caspase 3, 8 and 9 [ 78 , 80 ]. Another study proved that 5-FU-induced autophagy was inhibited in HCT116 and HT29 colon cancer cells co-treated with curcumin and 5-FU, via the downregulation of Akt and mTOR activities [ 81 ].…”

Section: Curcumin Combination Anticancer Therapy In Preclinical Studiesmentioning

confidence: 99%

Is Curcumin the Answer to Future Chemotherapy Cocktail?

et al. 2021

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The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure. The continuous use of conventional cancer therapies leads to chemoresistance, and a higher dose of treatment results in even greater toxicities among cancer patients. Therefore, the search for an alternative treatment modality is crucial to break this viscous cycle. This paper explores the suitability of curcumin combination treatment with other cancer therapies to curb cancer growth. We provide a critical insight to the mechanisms of action of curcumin, its role in combination therapy in various cancers, along with the molecular targets involved. Curcumin combination treatments were found to enhance anticancer effects, mediated by the multitargeting of several signalling pathways by curcumin and the co-administered cancer therapies. The preclinical and clinical evidence in curcumin combination therapy is critically analysed, and the future research direction of curcumin combination therapy is discussed.

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Curcumin Reverses 5-Fluorouracil Resistance by Promoting Human Colon Cancer HCT-8/5-FU Cell Apoptosis and Down-regulating Heat Shock Protein 27 and P-Glycoprotein

Cited by 45 publications

References 29 publications

Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo

Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo

The Role of SIRT5 and p53 Proteins in the Sensitivity of Colon Cancer Cells to Chemotherapeutic Agent 5-Fluorouracil

Is Curcumin the Answer to Future Chemotherapy Cocktail?

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Curcumin Reverses 5-Fluorouracil Resistance by Promoting Human Colon Cancer HCT-8/5-FU Cell Apoptosis and Down-regulating Heat Shock Protein 27 and P-Glycoprotein

Cited by 45 publications

References 29 publications

Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo

Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo

The Role of SIRT5&nbsp;and p53&nbsp;Proteins in the Sensitivity of Colon Cancer Cells to Chemotherapeutic Agent 5-Fluorouracil&nbsp;

Is Curcumin the Answer to Future Chemotherapy Cocktail?

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The Role of SIRT5 and p53 Proteins in the Sensitivity of Colon Cancer Cells to Chemotherapeutic Agent 5-Fluorouracil