Natural Products as a Tool to Modulate the Activity and Expression of Multidrug Resistance Proteins of Intestinal Barrier
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Updated: Aug 1, 2025
Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
Carlos Martins-Gomes1,2, Amélia M Silva1,2
1Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal.
Abstract:
The role of intestinal barrier homeostasis in an individual's general well-being has been widely addressed by the scientific community. Colorectal cancer is among the illnesses that most affect this biological barrier. While chemotherapy is the first choice to treat this type of cancer, multidrug resistance (MDR) is the major setback against the commonly used drugs, with the ATP-binding cassette transporters (ABC transporters) being the major players. The role of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), or breast cancer resistance protein (ABCG2) in the efflux of chemotherapeutic drugs is well described in cancer cells, highlighting these proteins as interesting druggable targets to reverse MDR, decrease drug dosage, and consequently undesired toxicity. Natural products, especially phytochemicals, have a wide diversity of chemical structures, and some particular classes, such as phenolic acids, flavonoids, or pentacyclic triterpenoids, have been reported as inhibitors of P-gp, MRP1, and ABCG2, being able to sensitize cancer cells to chemotherapy drugs. Nevertheless, ABC transporters play a vital role in the cell's defense against xenobiotics, and some phytochemicals have also been shown to induce the transporters' activity. A balance must be obtained between xenobiotic efflux in non-tumor cells and bioaccumulation of chemotherapy drugs in cancer cells, in which ABC transporters are essential and natural products play a pivotal role that must be further analyzed. This review summarizes the knowledge concerning the nomenclature and function of ABC-transporters, emphasizing their role in the intestinal barrier cells. In addition, it also focuses on the role of natural products commonly found in food products, e.g., phytochemicals, as modulators of ABC-transporter activity and expression, which are promising nutraceutical molecules to formulate new drug combinations to overcome multidrug resistance.
Insights
Natural products can help overcome chemotherapy resistance in colorectal cancer by modulating ATP-binding cassette (ABC) transporters. Understanding these interactions is key to developing new treatments and reducing drug toxicity.
Area of Science:
- Gastroenterology and Oncology
- Pharmacology and Natural Products
Background:
- Intestinal barrier homeostasis is crucial for overall health.
- Colorectal cancer significantly impacts the intestinal barrier.
- Multidrug resistance (MDR) to chemotherapy is a major challenge in cancer treatment, largely mediated by ATP-binding cassette (ABC) transporters like P-glycoprotein (P-gp), MRP1, and ABCG2.
Purpose of the Study:
- To review the role of ABC transporters in intestinal barrier cells.
- To explore the potential of natural products, particularly phytochemicals, in modulating ABC transporter activity and expression.
- To highlight nutraceuticals as potential agents to overcome MDR in cancer therapy.
Main Methods:
- Literature review on ABC transporter nomenclature, function, and role in MDR.
- Analysis of studies on natural products (phenolic acids, flavonoids, pentacyclic triterpenoids) as modulators of ABC transporters.
- Examination of the dual role of phytochemicals in inducing or inhibiting ABC transporter activity.
Main Results:
- ABC transporters (P-gp, MRP1, ABCG2) are key players in chemotherapy efflux and MDR.
- Certain phytochemicals can inhibit ABC transporters, sensitizing cancer cells to chemotherapy.
- Some phytochemicals can also induce ABC transporter activity, necessitating a balanced approach.
Conclusions:
- ABC transporters play a critical role in both intestinal barrier function and cancer MDR.
- Natural products offer promising avenues for developing strategies to overcome MDR.
- Further research into natural product-ABC transporter interactions is needed to optimize combination therapies and reduce chemotherapy toxicity.
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