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Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance

Bao-Yuan Huang1, Yu Zeng1, Ying-Jie Li2

  • 1National Administration of Traditional Chinese Medicine Key Laboratory of Chinese Medicine Digital Quality Evaluation Technology, College of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.

International Journal of Oncology
|May 24, 2017
PubMed

Insights

Isocoryneine (Icory), a uncaria alkaloid, effectively reverses multidrug resistance (MDR) mediated by ABCB1 transporters. This natural compound enhances chemotherapy efficacy by inhibiting the efflux function of ABCB1, offering a promising strategy against cancer MDR.

Area of Science:

  • Pharmacology
  • Oncology
  • Natural Products Chemistry

Background:

  • Multidrug resistance (MDR) in cancer, primarily driven by ATP-binding cassette (ABC) transporter overexpression, leads to chemotherapy failure.
  • Uncaria alkaloids, derived from a traditional Chinese herbal medicine, are investigated for their potential to overcome MDR.

Purpose of the Study:

  • To screen uncaria alkaloids for their MDR-reversal activities, focusing on their interaction with ABCB1.
  • To elucidate the mechanism by which isocoryneine (Icory) reverses ABCB1-mediated MDR.

Main Methods:

  • Screening of uncaria alkaloids for MDR reversal in combination with doxorubicin.
  • Testing Icory's efficacy against ABCB1-overexpressing cell lines with various chemotherapeutic agents.
  • Investigating Icory's effect on doxorubicin intracellular accumulation and ABCB1 expression/localization.
  • Analyzing Icory's interaction with ABCB1 transporter binding sites.

Main Results:

  • All tested uncaria alkaloids showed MDR reversal efficacy with doxorubicin.
  • Icory selectively sensitized ABCB1-overexpressing cells to vincristine, doxorubicin, and paclitaxel, but not cisplatin.
  • Icory increased intracellular doxorubicin accumulation by blocking ABCB1 efflux, acting as a competitive substrate rather than inhibiting transporter expression.

Conclusions:

  • Icory effectively reverses ABCB1-mediated MDR by inhibiting the transporter's efflux function through competitive binding.
  • Uncaria alkaloids, particularly Icory, show potential as selective agents to enhance chemotherapy efficacy in ABCB1-overexpressing cancers.

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