Journal of Advanced Research

Journal of Advanced Research

Volume 6, Issue 1, January 2015, Pages 45-62
Journal of Advanced Research

Review
P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review

https://doi.org/10.1016/j.jare.2014.11.008 Get rights and content
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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.

Keywords

Multidrug resistance (MDR)
Multidrug resistance-associated protein 1 (MRP1)
Natural products
P-gp (P-glycoprotein)

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Hossam M. Abdallah, PhD, received his M. S. degree in Pharmacognosy and PhD in Chemistry of Natural Products from Faculty of Pharmacy, Cairo University. In 2013, he was promoted to Associate Professor of Pharmacognosy, Faculty of Pharmacy, Cairo University. Currently, he is working at Natural Products and alternative medicine Department, Faculty of Pharmacy, King Abdulaziz University. He has 29 peer-reviewed publications, a reviewer in several peer-reviewed journals in the field of natural products, a PI and CO-I in more than ten projects. He has a scientific communication with two international institutes.

Ahmed M. Al-Abd has graduated (2000) from Faculty of Pharmacy, Ain Shams University. He obtained his PhD degree (Pharmacology and Toxicology) from Beni-Suif University, Egypt in 2011. Currently, he is an Assistant Professor at King Abdulaziz University and visiting scholar in Bouvé College of Health Sciences, Northeastern University, USA. He is an author and co-author for more than 25 peer-reviewed publications; Co-inventor in 2 patents. Ahmed Al-Abd has a broad international scientific communication network (collaborator with more than 15 research institutes in more than 5 different countries worldwide).

Dr. Riham Salah El Dine was graduated at 1998 from Faculty of Pharmacy, Cairo University. Afterward, she worked as teaching assistant in Department of Pharmacognosy, Cairo University from 1998 to 2003. In 2004, she was enrolled as a PhD candidate in Institute of Natural Medicine, Toyama, Japan. She got her PhD under the supervision of Dr. Masao Hattori. After PhD, she was awarded a postdoctoral fellowship in the same laboratory for 6 months. From 2008 up to date, she is appointed as an Assistant Professor, Faculty of Pharmacy, Cairo University. She is a co-author of more than 17 peer-reviewed publications; and a reviewer for several peer-reviewed journals in the field of natural products.

Ali El Halawany, PhD, was graduated from Faculty of Pharmacy, Cairo University in 1996. He obtained his master degree in Pharmacognosy in 2002. In 2004, he was selected for MEXT scholarship by the Japanese government to be enrolled as PhD Candidate in Institute of Natural Medicine, Toyama, Japan. After finishing the PhD in 2007, he was awarded a COE scholarship in the same laboratory for 6 months followed by another 6 months as a visiting researcher. In 2009, he worked at Institute of Natural Medicine as a foreign researcher for 1 year till 2010. From April 2014 up to date, he is working as an Associate Professor, Department of Pharmacognosy, Cairo University. He is an author/co-author for more than 28 peer-reviewed publications; Co-inventor in 1 US patent, a member in the editorial board of BFOPCU journal and a reviewer for several peer-reviewed journals in the field of natural products.

Peer review under responsibility of Cairo University.

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