Strategies for overcoming ABC-transporters-mediated multidrug resistance (MDR) of tumor cells.

Borowski, Edward; Bontemps-Gracz, Maria; Piwkowska, Agnieszka

doi:10.18388/abp.2005_3421

Cited by 113 publications

(52 citation statements)

References 181 publications

(184 reference statements)

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“…Most of these proteins transport substrates via transmembrane domains using energy released by ATP hydrolysis at nucleotide‐binding domains. These transporters have been studied intensively in animals because many are involved in multi‐drug resistance, which inhibits the long‐term use of drugs for treatment of chronic diseases (Borowski et al. , 2005).…”

Section: Introductionmentioning

confidence: 99%

An ABCG/WBC‐type ABC transporter is essential for transport of sporopollenin precursors for exine formation in developing pollen

et al. 2010

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SUMMARYThe exine of the pollen wall shows an intricate pattern, primarily comprising sporopollenin, a polymer of fatty acids and phenolic compounds. A series of enzymes synthesize sporopollenin precursors in tapetal cells, and the precursors are transported from the tapetum to the pollen surface. However, the mechanisms underlying the transport of sporopollenin precursors remain elusive. Here, we provide evidence that strongly suggests that the Arabidopsis ABC transporter ABCG26/WBC27 is involved in the transport of sporopollenin precursors. Two independent mutations at ABCG26 coding region caused drastic decrease in seed production. This defect was complemented by expression of ABCG26 driven by its native promoter. The severely reduced fertility of the abcg26 mutants was caused by a failure to produce mature pollen, observed initially as a defect in pollenwall development. The reticulate pattern of the exine of wild-type microspores was absent in abcg26 microspores at the vacuolate stage, and the vast majority of the mutant pollen degenerated thereafter. ABCG26 was expressed specifically in tapetal cells at the early vacuolate stage of pollen development. It showed high co-expression with genes encoding enzymes required for sporopollenin precursor synthesis, i.e. CYP704B1, ACOS5, MS2 and CYP703A2. Similar to two other mutants with defects in pollen-wall deposition, abcg26 tapetal cells accumulated numerous vesicles and granules. Taken together, these results suggest that ABCG26 plays a crucial role in the transfer of sporopollenin lipid precursors from tapetal cells to anther locules, facilitating exine formation on the pollen surface.

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Section: Introductionmentioning

confidence: 99%

An ABCG/WBC‐type ABC transporter is essential for transport of sporopollenin precursors for exine formation in developing pollen

et al. 2010

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“…5,6 There is now a concerted effort to develop drugs that can overcome multiple drug resistance (MDR). 7,8 We had previously shown that the peroxisome-proliferator activated receptor gamma (PPARγ) agonist troglitazone (TRG), but not other thiazolidinediones, downregulated glyoxalase I gene expression in a variety of cell types. 9 Since overexpression of glyoxalase I is present in a number of cancers, increased expression of glyoxalase I is thought to contribute to drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Troglitazone reverses the multiple drug resistance phenotype in cancer cells

Davies

Juurlink²,

Harkness

2009

DDDT

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A major problem in treating cancer is the development of drug resistance. We previously demonstrated doxorubicin (DOX) resistance in K562 human leukemia cells that was associated with upregulation of glyoxalase 1 (GLO-1) and histone H3 expression. The thiazolidinedione troglitazone (TRG) downregulated GLO-1 expression and further upregulated histone H3 expression and post-translational modifi cations in these cells, leading to a regained sensitivity to DOX. Given the pleiotropic effects of epigenetic changes in cancer development, we hypothesized that TRG may downregulate the multiple drug resistance (MDR) phenotype in a variety of cancer cells. To test this, MCF7 human breast cancer cells and K562 cells were cultured in the presence of low-dose DOX to establish DOX-resistant cell lines (K562/DOX and MCF7/DOX). The MDR phenotype was confi rmed by Western blot analysis of the 170 kDa P-glycoprotein (Pgp) drug effl ux pump multiple drug resistance protein 1 (MDR-1), and the breast cancer resistance protein (BCRP). TRG markedly decreased expression of both MDR-1 and BCRP in these cells, resulting in sensitivity to DOX. Silencing of MDR-1 expression also sensitized MCF7/DOX cells to DOX. Use of the specifi c and irreversible peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 in the nanomolar range not only demonstrated that the action of TRG on MCF/DOX was PPARγ-independent, but indicated that PPARγ may play a role in the MDR phenotype, which is antagonized by TRG. We conclude that TRG is potentially a useful adjunct therapy in chemoresistant cancers.

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“…The occurrence of resistance to anticancer agents is a major obstacle for successful cancer chemotherapy. The emergence of resistance to anticancer drugs, in particular multidrug resistance (MDR), has made many of the available anticancer drugs ineffective . A glycoprotein, ABCB1, also known as P‐glycoprotein, is a membrane protein member of the ABC transporter superfamily.…”

Section: Figurementioning

confidence: 99%

Synthesis of an Orthogonally Protected Polyhydroxylated Cyclopentene from l‐Sorbose

Jones

Giralt

et al. 2016

Chemistry An Asian Journal

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The use of l-sorbose in the synthesis of functionalized cyclopentene derivatives was accomplished. These cyclopentene derivatives are related to those found in naturally occurring jatrophane frameworks and in other bioactive compounds. The formation of allyl α-l-sorbopyranoside was a key synthetic step. Regioselective introduction of protecting groups was followed by the hydrolysis of the allyl glycoside to furnish a fully protected acyclic l-sorbose derivative. This acyclic intermediate was subsequently used to give an orthogonally protected polyhydroxylated cyclopentene, which has potential for further synthesis of bioactive compounds. The protected cyclopentene itself showed a clear cytotoxic activity when tested against a panel of human cancer cell lines (HT29, LS174T, SW620, A549, and HeLa cells).

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Strategies for overcoming ABC-transporters-mediated multidrug resistance (MDR) of tumor cells.

Cited by 113 publications

References 181 publications

An ABCG/WBC‐type ABC transporter is essential for transport of sporopollenin precursors for exine formation in developing pollen

An ABCG/WBC‐type ABC transporter is essential for transport of sporopollenin precursors for exine formation in developing pollen

Troglitazone reverses the multiple drug resistance phenotype in cancer cells

Synthesis of an Orthogonally Protected Polyhydroxylated Cyclopentene from l‐Sorbose

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