Influence of multidrug resistance and drug transport proteins on chemotherapy drug metabolism

Joyce, Helena; McCann, Andrew; Clynes, Martin; Larkin, Annemarie

doi:10.1517/17425255.2015.1028356

Cited by 63 publications

(52 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MDR development is typically associated with the development of a series of structurally-associated compounds for cancer treatment, leading to the development of structural and functional cross-resistance (31). Despite the continuous introduction of novel chemotherapeutic agents, overcoming MDR remains a challenge in cancer chemotherapy (32,33).…”

Section: Discussionmentioning

confidence: 99%

“…These drug transporters recognize numerous functionally and structurally independent anticancer drugs and, therefore, can expel intracellular drugs efficiently. The overexpression of these proteins can confer cancer cells with multidrug resistance (12,13). The development of strategies to overcome the side effects and drug resistance of antitumor drugs is an ongoing challenge for medical workers.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the efficacy of AD is associated with drug concentration, which is also associated with drug resistance. The inhibition of tumor cell efflux can effectively increase the sensitivity of tumor cells to chemotherapeutic drugs (15,13). Therefore, agents with high efficacy and few side effects are urgently required in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Shikonin enhances Adriamycin antitumor effects by inhibiting efflux pumps in A549 cells

Liu¹,

Sun²

2017

Oncology Letters

View full text Add to dashboard Cite

Abstract. Shikonin (SHK) is a natural naphthoquinone pigment isolated from Lithospermum erythrorhizon, that has been reported to suppress the growth of a number of cancer cell types. Adriamycin (AD) is typically used as an effective anticancer agent; however, it has the propensity to induce drug resistance. The aim of the present study was to investigate the effects of SHK alone and in combination with AD on lung adenocarcinoma cells and the underlying molecular mechanisms of their effects. Colony formation, MTT and propidium iodide staining assays demonstrated that the co-treatment of A549 cells with SHK and AD significantly decreased cell viability and potently induced apoptosis. The mitochondrial membrane potential was assessed using 5,5', 6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine iodide staining and fluorescence microscopy. Cells co-treated with SHK and AD exhibited marked mitochondrial membrane damage. In addition, co-treatment with SHK and AD significantly reduced ATP levels in A549 cells compared with the control. Western blot analysis revealed that SHK enhanced the antitumor effects of AD by inhibiting the expression of ATP-binding cassette transporters. These results suggest that the inhibition of glycolysis could be an effective approach for lung cancer treatment. Therefore, SHK has the potential to be used as an anticancer agent in the treatment of lung adenocarcinoma, and thus warrants further investigation and development.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Shikonin enhances Adriamycin antitumor effects by inhibiting efflux pumps in A549 cells

Liu¹,

Sun²

2017

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…For example, the antifungal ketoconazole, a potent inhibitor of CYP3A4, causes drug-drug interactions with drugs that are substrates of CYP3A4 (Xiaoyang et al 2015). However, undesired drug-drug interactions can also be caused by transporters (Kim et al 1998;Li et al 2014;Joyce et al 2015;Wen et al 2016). Some drug interactions, previously believed to be P450-mediated, are now considered at least in part due to the inhibition of transport proteins.…”

Section: Discussionmentioning

confidence: 99%

Effects of berberine on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism

Liu

Xie

et al. 2016

Pharmaceutical Biology

View full text Add to dashboard Cite

(2016) Effects of berberine on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism, Pharmaceutical Biology, 54:12, 2886-2894, DOI: 10.1080/13880209.2016 Context: Losartan and berberine (BBR) are often simultaneously used for the treatment of senile diabetic nephropathy in clinics. However, the potential herb-drug interaction between losartan and BBR is unknown. Objective: This study investigates the influence of BBR on the pharmacokinetics of losartan and EXP3174, and investigates the effects of BBR on the metabolic stability of losartan. Materials and methods: The pharmacokinetic profiles losartan and EXP3174 of orally administered losartan (10 mg/kg) with and without pretreatment with BBR (20 mg/kg) within 24 h were determined in Sprague-Dawley rats. The inhibitory effects of BBR on the metabolic stability of losartan were investigated using rat liver microsomes. Results: The C max (1.26 ± 0.37 versus 1.96 ± 0.45 mg/L) and the AUC (0-t) (8.25 ± 0.89 versus 12.70 ± 1.42 mg h/L) of losartan were significantly (p < 0.05) increased by BBR compared to the control, while the C max (0.97 ± 0.15 versus 0.77 ± 0.06 mg/L) of EXP3174 was significantly decreased compared to the control (p < 0.05). The T max of losartan was prolonged from 0.41 ± 0.12 to 0.52 ± 0.18 h, but the difference was not significant. However, the T max of EXP3174 was decreased significantly (p < 0.05) from 8.14 ± 0.36 to 3.33 ± 0.28 h. The metabolic stability of losartan was increased from 37.4 to 59.6 min. Discussion and conclusion: We infer that BBR might increase the plasma concentration of losartan and decrease the concentration of EXP3174 through inhibiting the activity of CYP3A4 or CYP2C9. ARTICLE HISTORY

show abstract

“…[1][2][3][4][5][6][7] Nearly 90% of tumor cells gradually become insensitive and MDR occurs after repeated exposure of drugs to the tumor cells for a certain time. 8,9 Tumor cells can survive after exposure to chemotherapy drugs to produce MDR through inhibition of apoptosis and other ways.…”

Section: Introductionmentioning

confidence: 99%

Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance

Guang

Shi

et al. 2015

IJN

View full text Add to dashboard Cite

Nowadays, multidrug resistance and side effects of drugs limit the effectiveness of chemotherapies in clinics. P-glycoprotein (P-gp) (MDR1), as a member of the ATP-binding cassette family, acts on transporting drugs into cell plasma across the membrane of cancer cells and leads to the occurrence of multidrug resistance, thus resulting in the failure of chemotherapy in cancer. The main aims of this research were to design a nanodelivery system for accomplishing the effective co-delivery of gene and antitumor drug and overcoming multidrug resistance effect. In this study, shMDR1 and gefitinib-encapsulating chitosan nanoparticles with sustained release, small particle size, and high encapsulation efficiency were prepared. The serum stability, protection from nuclease, and transfection efficiency of gene in vitro were investigated. The effects of co-delivery of shMDR1 and gefitinib in nanoparticles on reversing multidrug resistance were also evaluated by investigating the cytotoxicity, cellular uptake mechanism, and cell apoptosis on established gefitinib-resistant cells. The results demonstrated that chitosan nanoparticles entrapping gefitinib and shMDR1 had the potential to overcome the multidrug resistance and improve cancer treatment efficacy, especially toward resistant cells.

show abstract

Influence of multidrug resistance and drug transport proteins on chemotherapy drug metabolism

Cited by 63 publications

References 134 publications

Shikonin enhances Adriamycin antitumor effects by inhibiting efflux pumps in A549 cells

Shikonin enhances Adriamycin antitumor effects by inhibiting efflux pumps in A549 cells

Effects of berberine on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism

Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance

Contact Info

Product

Resources

About