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Wallichinine reverses ABCB1-mediated cancer multidrug resistance

Min Lv1, Jian-Ge Qiu2, Wen-Ji Zhang2

  • 1Institute of Materia Medica, Zhejiang Chinese Medical University Hangzhou, Zhejiang, China.

American Journal of Translational Research
|August 11, 2016
PubMed

Insights

Wallichinine, a natural compound, reverses cancer multidrug resistance (MDR) by inhibiting the ABCB1 transporter. This enhances chemotherapy effectiveness against ABCB1-overexpressing cancer cells, offering potential for new MDR reversal agents.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Natural Products Chemistry

Background:

  • ABCB1 transporter overexpression is a primary cause of cancer multidrug resistance (MDR).
  • Wallichinine, a compound from Piper wallichii, is known as a platelet-activating factor receptor antagonist.
  • Investigating natural products for MDR reversal is crucial for improving cancer therapy.

Purpose of the Study:

  • To investigate the effect of wallichinine on ABCB1-mediated cancer multidrug resistance.
  • To explore wallichinine's potential as a novel agent for reversing MDR.

Main Methods:

  • Assessing the potentiation of ABCB1 substrate drugs (vincristine, doxorubicin) by wallichinine in ABCB1-overexpressing cancer cells.
  • Evaluating wallichinine's effect on non-ABCB1 substrate drug (cisplatin) sensitivity.
  • Measuring intracellular drug accumulation and ABCB1 ATPase activity.
  • Computational prediction of wallichinine's binding mode within the ABCB1 transporter.

Main Results:

  • Wallichinine significantly enhanced the efficacy of vincristine and doxorubicin in ABCB1-overexpressing cancer cells, affecting growth inhibition, cell cycle arrest, and apoptosis.
  • Wallichinine did not alter the sensitivity to cisplatin, indicating specificity for ABCB1 substrates.
  • Wallichinine inhibited ABCB1 drug-efflux activity, increasing intracellular doxorubicin and rhodamine 123 accumulation.
  • Wallichinine stimulated ABCB1 ATPase activity without changing ABCB1 expression levels.
  • Predicted binding mode revealed hydrophobic interactions of wallichinine within the ABCB1 drug-binding cavity.

Conclusions:

  • Wallichinine effectively reverses ABCB1-mediated multidrug resistance in cancer cells.
  • Wallichinine acts by inhibiting ABCB1 transporter function and stimulating its ATPase activity.
  • This study highlights wallichinine as a promising natural product for developing new MDR reversal strategies in cancer treatment.
Keywords:
ABCB1Wallichininecancermultidrug resistance

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