Dynamic vs static ABCG2 inhibitors to sensitize drug resistant cancer cells

Hui Peng, Jing Qi, Zizheng Dong, Jian-Ting Zhang

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Human ABCG2, a member of the ATP-binding cassette transporter superfamily, plays a key role in multidrug resistance and protecting cancer stem cells. ABCG2-knockout had no apparent adverse effect on the development, biochemistry, and life of mice. Thus, ABCG2 is an interesting and promising target for development of chemo-sensitizing agents for better treatment of drug resistant cancers and for eliminating cancer stem cells. Previously, we reported a novel two mode-acting ABCG2 inhibitor, PZ-39, that induces ABCG2 degradation in addition to inhibiting its activity. In this manuscript, we report our recent progresses in identifying two different groups of ABCG2 inhibitors with one inhibiting only ABCG2 function (static) and the other induces ABCG2 degradation in lysosome in addition to inhibiting its function (dynamic). Thus, the inhibitor-induced ABCG2 degradation may be more common than we previously anticipated and further investigation of the dynamic inhibitors that induce ABCG2 degradation may provide a more effective way of sensitizing ABCG2-mediated MDR in cancer chemotherapy.

Original languageEnglish
Article numbere15276
JournalPLoS One
Volume5
Issue number12
DOIs
StatePublished - 2010

Fingerprint

Neoplastic Stem Cells
Corrosion inhibitors
Cells
Degradation
drugs
ATP-Binding Cassette Transporters
degradation
Multiple Drug Resistance
Lysosomes
Stem cells
Pharmaceutical Preparations
Biochemistry
drug therapy
stem cells
Neoplasms
Drug Therapy
ABC transporters
neoplasms
Chemotherapy
multiple drug resistance

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Dynamic vs static ABCG2 inhibitors to sensitize drug resistant cancer cells. / Peng, Hui; Qi, Jing; Dong, Zizheng; Zhang, Jian-Ting.

In: PLoS One, Vol. 5, No. 12, e15276, 2010.

Research output: Contribution to journalArticle

Peng, Hui ; Qi, Jing ; Dong, Zizheng ; Zhang, Jian-Ting. / Dynamic vs static ABCG2 inhibitors to sensitize drug resistant cancer cells. In: PLoS One. 2010 ; Vol. 5, No. 12.
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