Wogonin reverses multi-drug resistance of human myelogenous leukemia K562/A02 cells via downregulation of MRP1 expression by inhibiting Nrf2/ARE signaling pathway

Xu, Xuefen; Zhang, Yi; Li, Wei; Hua, Miao; Zhang, Haiwei; Zhou, Yuxin; Li, Zhiyu; Qin, You; Zhao, Li; Guo, Qing

doi:10.1016/j.bcp.2014.09.008

Cited by 79 publications

(60 citation statements)

References 43 publications

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“…MRP1, an ATP-dependent molecular pump, is a member of the ABC transporter protein family and is able to decrease intracellular drug accumulation, thus decreasing the cellular toxicity of various chemotherapeutic agents, including ADR, daunorubicin, epirubicin, mitoxantrone, bisantrene, vincristine, vinblastine, etoposide and paclitaxel (11,31). In the present study, western blot analysis demonstrated that treatment with solanine significantly decreased MRP1 protein expression compared with treatment with ADR alone in K562/ADM cells.…”

Section: Discussionmentioning

confidence: 99%

“…non-resistant cell lines (11). K562/ADM cells were identified to express MRP1 protein at high levels (11). Western blot analysis demonstrated that MRP1 protein expression was significantly decreased in K562/ADM cells following treatment with 5 or 10 µg/ml solanine compared with the untreated cells (P<0.05; Fig.…”

Section: Solanine Increases the Intracellular Accumulation Of Adrmentioning

confidence: 99%

“…These results indicate that solanine increases the sensitivity of K562/ADM cells to ADR by increasing intracellular ADR accumulation. non-resistant cell lines (11). K562/ADM cells were identified to express MRP1 protein at high levels (11).…”

Section: Solanine Increases the Intracellular Accumulation Of Adrmentioning

confidence: 99%

“…Increased MRP1 expression leads to a reduction in the concentration of chemotherapeutics inside tumor cells, resulting in the decreased efficacy of these agents (5)(6)(7)(8)(9)(10). MRP1 has been associated with resistance to various chemotherapeutic agents, including Adriamycin ® (ADR; doxorubicin), methotrexate, etoposide and vincristine (11).…”

Section: Introductionmentioning

confidence: 99%

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Solanine reverses multidrug resistance in human myelogenous leukemia K562/ADM cells by downregulating MRP1 expression

Xing

Zhu

et al. 2018

Oncol Lett

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Abstract. Multidrug resistance (MDR) in leukemia cells is a major obstacle to chemotherapeutic treatment. High expression and constitutive activation of multidrug resistance protein 1 (MRP1) has been associated with the development of resistance to anticancer drugs in a number of tumor types. The activity of c-Jun N-terminal kinase 1 (JNK1) is associated with the occurrence of MDR and MRP1 expression. The present study aimed to investigate the ability of solanine to resensitize the Adriamycin ® (ADR)-resistant human myelogenous leukemia cell line K562/ADM to ADR. Results of the Cell Counting Kit-8 assay demonstrated that solanine inhibited K562/ADM cell proliferation. K562/ADM cell sensitivity to ADR was increased following treatment with solanine, indicated by increased intracellular accumulation of ADR. Western blotting demonstrated that treatment with solanine led to reduced MRP1 protein expression, suggesting that solanine-induced ADR accumulation is due to the downregulation of MRP1 expression. Solanine-mediated MRP1 downregulation was observed to be dependent on the JNK signaling pathway. In conclusion, the results of the present study suggest that solanine reverses MDR in K562/ADM cells and may represent a novel therapeutic agent for the treatment of human myelogenous leukemia.

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Section: Discussionmentioning

confidence: 99%

Section: Solanine Increases the Intracellular Accumulation Of Adrmentioning

confidence: 99%

Section: Solanine Increases the Intracellular Accumulation Of Adrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Solanine reverses multidrug resistance in human myelogenous leukemia K562/ADM cells by downregulating MRP1 expression

Xing

Zhu

et al. 2018

Oncol Lett

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“…This inspires us to block the PPP or glutamine metabolism to decrease the NADPH and nucleotide biosynthesis, eventually enhance the efficacy the chemotherapy agents. Knockdown of Nrf2 by miR-340 mimics, or Wogonin can overcome resistance to chemotherapy through suppressing Nrf2-dependent antioxidant pathway in cancer treatment [114][115][116].…”

Section: Targeting Anabolic Processmentioning

confidence: 99%

The greedy nature of mutant RAS: a boon for drug discovery targeting cancer metabolism?

Lv¹,

Wang²,

Chang³

et al. 2016

ABBS

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RAS oncogene mutations are frequently detected in human cancers. Among RAS-mediated tumorigenesis, KRAS-driven cancers are the most frequently diagnosed and resistant to current therapies. Despite more than three decades of intensive efforts, there are still no specific therapies for mutant RAS proteins. While trying to block those well-established downstream pathways, such as the RAF-MAPK pathway and the PI3K-AKT pathway, attentions have been paid to potential effects of RAS on metabolic pathways and the feasibility for targeting these pathways. Recent studies have proved that RAS not only promotes aerobic glycolysis and glutamine metabolism reprograming to provide energy, but it also facilitates branched metabolism pathways, autophagy, and macropinocytosis. These alterations generate building blocks for tumor growth and strengthen antioxidant defense in tumor cells. All of these metabolic changes meet different demands of RAS-driven cancers, making them distinct from normal cells. Indeed, some achievements have been made to inhibit tumor growth through targeting specific metabolism rewiring in preclinical models. Although there is still a long way to elucidate the landscape of altered metabolism, we believe that specific metabolic enzymes or pathways could be therapeutically targeted for selective inhibition of RAS-driven cancers.

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Low oxygen tension differentially regulates the expression of placental solute carriers and ABC transporters

Gorczyca

Bircsak

et al. 2020

FEBS Letters

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Low oxygen concentration, or hypoxia, is an important physiological regulator of placental function including chemical disposition. Here, we compared the ability of low oxygen tension to alter the expression of solute carriers (SLC) and ABC transporters in two human placental models, namely BeWo cells and term placental explants. We found that exposure to low oxygen concentration differentially regulates transporter expression in BeWo cells, including downregulation of ENT1, OATP4A1, OCTN2, BCRP, and MRP2/3/5, and upregulation of CNT1, OAT4, OATP2B1, SERT, SOAT, and MRP1. Similar upregulation of MRP1 and downregulation of MRP5 and BCRP were observed in explants, whereas uptake transporters were decreased or unchanged. Furthermore, a screening of transcriptional regulators of transporters revealed that hypoxia leads to a decrease in the mRNA levels of aryl hydrocarbon receptor, nuclear factor erythroid 2‐related factor 2, and retinoid x receptor alpha in both human placental models. These data suggest that transporter expression is differentially regulated by oxygen concentration across experimental human placental models.

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Wogonin reverses multi-drug resistance of human myelogenous leukemia K562/A02 cells via downregulation of MRP1 expression by inhibiting Nrf2/ARE signaling pathway

Cited by 79 publications

References 43 publications

Solanine reverses multidrug resistance in human myelogenous leukemia K562/ADM cells by downregulating MRP1 expression

Solanine reverses multidrug resistance in human myelogenous leukemia K562/ADM cells by downregulating MRP1 expression

The greedy nature of mutant RAS: a boon for drug discovery targeting cancer metabolism?

Low oxygen tension differentially regulates the expression of placental solute carriers and ABC transporters

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