8-Prenylnaringenin is an inhibitor of multidrug resistance-associated transporters, P-glycoprotein and MRP1

Wesołowska, Olga; Wiśniewski, Jerzy; Środa, Kamila; Krawczenko, Agnieszka; Bielawska‐Pohl, Aleksandra; Paprocka, Maria; Duś, Danuta; Michalak, Krystyna

doi:10.1016/j.ejphar.2010.06.069

Cited by 64 publications

(56 citation statements)

References 48 publications

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“…All phosphine oxides( 10-13 and 29-33)a sw ell as methyl and ethyl phosphinates( 64-71)e xhibited nearly equal activity against both doxorubicin-resistant and doxorubicin-sensitive cell lines (LoVo/DX and LoVo, respectively), whereas Doxo showedo ver 30-foldl ower activity on the drug-resistants ubline. As the observed drug resistance of LoVo/DXc ells is primarily the result of ah igh level of multidrug-resistance-associated ABC transporters (P-glycoproteins, P-gp), [58] we conclude that the synthesized compounds are not sufficients ubstrates for these pumps. These findings are consistentw ith our previous studies on phosphonates in whichw ep rovedt hat introducing ap hosphonate moiety to the backbone of ITCs potentiate their activity,b ut no clear SAR can be highlighted.…”

Section: In Vitro Biological Studiesmentioning

confidence: 73%

Design, Synthesis, and Evaluation of ω‐(Isothiocyanato)alkylphosphinates and Phosphine Oxides as Antiproliferative Agents

et al. 2017

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A series of 21 novel, structurally diverse ω‐(isothiocyanato)alkylphosphinates and phosphine oxides (ITCs) were designed and synthesized in moderate to good yields. The synthesized compounds were evaluated for in vitro antiproliferative activity using LoVo and LoVo/DX cancer cell lines. The biological activity of the synthesized compounds was higher than that of natural isothiocyanates such as benzyl isothiocyanate or sulforaphane. The antiproliferative activity of selected ITCs was also tested on selected cancer cell lines: A549, MESSA and MESSA/DX‐5, HL60 and HL60MX2, BALB/3T3, and 4T1. These compounds were assessed for their mechanism of action as inducers of cell‐cycle arrest and apoptosis. Ethyl (6‐isothiocyanatohexyl)(phenyl)phosphinate (71) was tested in vivo on the 4T1 cell line and demonstrated moderate antitumor activity, similar to that benzyl isothiocyanate and cyclophosphamide.

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Section: In Vitro Biological Studiesmentioning

confidence: 73%

Design, Synthesis, and Evaluation of ω‐(Isothiocyanato)alkylphosphinates and Phosphine Oxides as Antiproliferative Agents

et al. 2017

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“…In addition, MRP1 can even shift drugs out of cells into the extracellular fluid by vesicle transportation or exocytosis (14,18,19). Numerous studies have shown that inhibition of MRP1 expression by a variety of methods eased the development of drug resistance, thus supported clinical chemotherapy (20)(21)(22). Regarding the expression of MRP1 in esophageal cancer, it has been demonstrated that MRP1 often overexpressed in different esophageal cancer cell lines or cancer tissues of patients (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1

et al. 2012

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Abstract. Multidrug resistance is one of the major causes limiting the efficacy of chemotherapeutic agents to control esophageal cancer. Herein, we investigated that the effect and mechanism of tetrandrine (TET) in the human esophageal squamous carcinoma cisplatin-resistant cell line YES-2/DDP. The human esophageal squamous carcinoma cisplatin-resistant cell line YES-2/DDP was isolated by stepwise selection in increasing concentrations of cisplatin. The CCK-8 method was carried out to measure the cell viability when cells were exposed to TET with or without cisplatin, and the IC 50 and resistance index (RI) of cisplatin was then calculated. Real-time RT-PCR and western blotting were used to detect the mRNA and protein expression of multidrug resistance 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP), respectively. Flow cytometry was adopted to determine CMFDA efflux and cell apoptosis, respectively. The resulting cell line YES-2/ DDP was 16.4-fold resistant to cisplatin, the cytotoxicity of cisplatin to YES-2/DDP cells was enhanced by TET in a dosedependent manner. Further, it was found that the expression of MDR1 and BCRP was similar in different treated cells. In contrast, the expression of MRP1 was markedly increased in YES-2/DDP cells, which was dose-dependently decreased by TET. In agreement with the results, MRP1 activity was also reversed by TET. In conclusion, TET possesses a reversal effect on drug resistance in YES-2/DDP cells through downregulation of MRP1, and has the potential to be an adjunct to chemotherapy for esophageal cancer. IntroductionChemotherapy is regarded as an important line of defense against esophageal cancer which is one of the most aggressive and lethal malignancies. However, on account of drug resistance especially multi-drug resistance (MDR), only a limited proportion of cancer patients respond favorably to commonly used chemotherapeutic drugs (1). With respect to the mechanisms of drug resistance, ATP-binding cassette (ABC) transporters, such as ABCB1/multidrug resistance 1 (MDR1), ABCC1/multidrug resistance-associated protein 1 (MRP1) and ABCG2/breast cancer resistance protein (BCRP), mediate energy-dependent drug efflux and play a main role in chemoresistance (2,3). Therefore, it seems imperative to find new drugs or methods especially targeting ABC transporters to reverse tumor drug-resistance.Tetrandrine (TET) (Fig. 1), a bis-benzylisoquinoline alkaloid isolated from the Chinese herb 'Han-Fang-Ji' (Radix Stephania tetrandra S. Moore), has been found to have immunosuppressive, free radical scavenging and anti-inflammatory activities (4-6). Furthermore, many recent studies have shown that TET exerts antitumor effects (7,8). In addition to inhibiting proliferation and inducing apoptosis of several cancer types, TET has exhibited potential as an adjunct to chemotherapy in many drug-resistant cancer cell lines (9,10). However, it remains unclear whether TET can reverse ABC transporter-mediated drug efflux. Moreover, it is als...

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“…[21][22][23] Therefore, our study focused on providing an insight into the ATPase activity P-gp has an ATP-binding region that is essential for substrate transport, and hydrolysis of ATP by P-gp ATPase is critical for restoring the transporter to its active conformational state. Therefore, ATPase activity plays an important role in reflecting the interaction between compounds and the drug efflux transporter.…”

Section: Mechanism Of Action Of Qnmentioning

confidence: 99%

Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes

Xu¹,

Qiu²

2015

IJN

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The use of vincristine (VCR) to treat cancer has been limited by its dose-dependent toxicity and development of drug resistance after repeated administrations. In this study, we investigated the mechanism by which quinine hydrochloride (QN) acts as a sensitizer for VCR. Our experiments used three kinds of multidrug-resistant cancer cells and demonstrated that QN worked by inducing intracellular depletion of adenosine triphosphate, increasing adenosine triphosphatase activity, and decreasing P-glycoprotein expression. Based on these results, we designed and prepared a VCR and QN codelivery liposome (VQL) and investigated the effect of coencapsulated QN on the in vitro cytotoxicity of VCR in cells and three-dimensional multicellular tumor spheroids. The antitumor effects of the formulation were also evaluated in multidrug-resistant tumor-bearing mice. The results of this in vivo study indicated that VQL could reverse VCR resistance. In addition, it reduced tumor volume 5.4-fold when compared with other test groups. The data suggest that VQL could be a promising nanoscaled therapeutic agent to overcome multidrug resistance, and may have important clinical implications for the treatment of cancer.

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8-Prenylnaringenin is an inhibitor of multidrug resistance-associated transporters, P-glycoprotein and MRP1

Cited by 64 publications

References 48 publications

Design, Synthesis, and Evaluation of ω‐(Isothiocyanato)alkylphosphinates and Phosphine Oxides as Antiproliferative Agents

Design, Synthesis, and Evaluation of ω‐(Isothiocyanato)alkylphosphinates and Phosphine Oxides as Antiproliferative Agents

Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1

Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes

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