title: P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review.
abstract: Resistance of solid tumors to treatment is significantly attributed to pharmacokinetic reasons at both cellular and multi-cellular levels. Anticancer agent must be bio-available at the site of action in a cytotoxic concentration to exert its proposed activity. P-glycoprotein (P-gp) is a member of the ATP-dependent membrane transport proteins; it is known to pump substrates out of cells in ATP-dependent mechanism. The over-expression of P-gp in tumor cells reduces the intracellular drug concentrations, which decreases the cytotoxicity of a broad spectrum of antitumor drugs. Accordingly, P-gp inhibitors/blockers are potential enhancer for the cellular bioavailability of several clinically important anticancer drugs such as, anthracyclines, taxanes, vinca alkaloids, and podophyllotoxins. Besides several chemically synthesized P-gp inhibitors/blockers, some naturally occurring compounds and plant extracts were reported for their modulation of multidrug resistance; however, this review will focus only on major classes of naturally occurring inhibitors viz., flavonoids, coumarins, terpenoids, alkaloids and saponins.
authors: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia ; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors: Hossam M
authors: HM
authors: Abdallah
authors: Pharmacology Department, Medical Division, National Research Center, Giza, Egypt ; Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors: Ahmed M
authors: AM
authors: Al-Abd
authors: Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors: Riham Salah
authors: RS
authors: El-Dine
authors: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia ; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors: Ali M
authors: AM
authors: El-Halawany
keywords: Multidrug resistance (MDR); Multidrug resistance-associated protein 1 (MRP1); Natural products; P-gp (P-glycoprotein)