Euphorbia factor L1 reverses ABCB1-mediated multidrug resistance involving interaction with ABCB1 independent of ABCB1 downregualtion

J Cell Biochem. 2011 Apr;112(4):1076-83. doi: 10.1002/jcb.23021.

Abstract

Euphorbia factor L1 (EFL1) belongs to diterpenoids of genus Euphorbia. In this article, its reversal activity against ABCB1-mediated MDR in KBv200 and MCF-7/adr cells was reported. However, EFL1 did not alter the sensitivity of KB and MCF-7 cells to chemotherapeutic agents. Meanwhile, EFL1 significantly increased accumulation of doxorubicin and rhodamine 123 in KBv200 and MCF-7/adr cells, showing no significant influence on that of KB and MCF-7 cells. Furthermore, EFL1 could enhance the ATP hydrolysis activity of ABCB1 stimulated by verapamil. At the same time, EFL1 inhibited the efflux of ABCB1 in KBv200 and MCF-7/adr cells. In addition, EFL1 did not downregulate expression of ABCB1 in KBv200 and MCF-7/adr cells either in mRNA or protein level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Antibiotics, Antineoplastic / metabolism
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / pharmacology
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Diterpenes / chemistry
  • Diterpenes / metabolism
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Neoplasm / drug effects*
  • Euphorbia / chemistry*
  • Flow Cytometry
  • Humans
  • Hydrolysis / drug effects
  • Molecular Structure
  • Phenylpropionates / chemistry
  • Phenylpropionates / pharmacology*
  • Plant Extracts / chemistry
  • Plant Extracts / metabolism
  • Plant Extracts / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhodamine 123 / metabolism
  • Rhodamine 123 / pharmacokinetics

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • Diterpenes
  • Phenylpropionates
  • Plant Extracts
  • euphorbia factor L1
  • Rhodamine 123
  • Doxorubicin
  • Adenosine Triphosphate
  • Adenosine Triphosphatases