Transporter-mediated multidrug resistance and its modulation by Chinese medicines and other herbal products

Area of Science:

• Pharmacology and Oncology
• Molecular Biology
• Natural Product Chemistry

Background:

• Multidrug resistance (MDR) is a major cause of cancer chemotherapy failure.
• Overexpression of ATP-binding cassette (ABC) transporters like P-glycoprotein (P-gp), MRP1, and BCRP mediates MDR by increasing drug efflux.
• These transporters are often found in recurrent cancer cells and cancer stem cells, highlighting their clinical significance.

Purpose of the Study:

• To review the role of P-gp, MRP1, and BCRP in cancer drug resistance.
• To explore the mechanisms of action for MDR modulators.
• To summarize methods for identifying and evaluating novel modulators of transporter-mediated MDR.
• To assess the effects of Chinese medicines (CMs) and natural products on ABC transporters and MDR.

Main Methods:

• Literature review of studies on MDR mechanisms and modulators.
• Analysis of the contribution of specific ABC transporters (P-gp, MRP1, BCRP) to MDR.
• Evaluation of identified MDR modulators from CMs and natural products.
• Review of methods used for the identification and assessment of novel MDR modulators.

Main Results:

• P-gp, MRP1, and BCRP are key ABC transporters driving MDR in cancer.
• Various CMs and their active components demonstrate potent MDR modulating effects.
• These natural products can inhibit ABC transporter activity, reducing drug efflux and enhancing chemosensitivity.
• Established methods exist for the identification and evaluation of novel MDR modulators.

Conclusions:

• CMs and natural products are promising sources for developing novel MDR modulators.
• Targeting ABC transporters with natural compounds offers a strategy to overcome drug resistance in cancer.
• Further research into CM-derived MDR modulators could lead to more effective and less toxic cancer therapies.