Enhancing Activity of Anticancer Drugs in Multidrug Resistant Tumors by Modulating P-Glycoprotein through Dietary Nutraceuticals

Abstract

Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs.

Piperine sensitizes radiation‐resistant cancer cells towards radiation and promotes intrinsic pathway of apoptosis

“…Black pepper is one of the most common spices consumed by a large number of populations worldwide. Piperine has been reported to enhance the activity of the anticancer drugs in various drug‐resistant cancer cells (Khan, Maryam, Mehmood, Zhang, & Ma, 2015; Li, Krstin, Wang, & Wink, 2018; Manayi, Nabavi, Setzer, & Jafari, 2018; Syed et al., 2017), including colorectal cancer cell line (Bolat et al., 2020). Several effector mechanism of piperine against cancer cell line such as influencing redox homeostatsis, autophagy, cancer stem cell inhibition and endoplasmic reticulum modulation has been postulated earlier (Rather & Bhagat, 2018).…”

BioPerine Encapsulated Nanoformulation for Overcoming Drug-Resistant Breast Cancers

“…In the lines of developing innovative targeted therapies against P-gp nutraceutical/dietary compounds have proven to be safer alternatives in reversing multidrug resistance in cancer. Among the plethora of natural dietary compounds available for P-gp inhibition, [13] piperine, a major plant alkaloid present in black pepper and long pepper accounted enhanced inhibitory P-gp efflux activity in a number of drug-resistant cancer cell lines [ 14 , 15 ]. From inhibiting drug transporters such as P-gp, eliciting anti-inflammatory, anti-arthritic, anti-tumor to being used as a bio enhancer with various natural compounds [ 16 , 17 ] and therapeutically diverse compounds the effects of piperine is wide and well-established.…”

P-Glycoprotein 1 Affects Chemoactivities of Resveratrol against Human Colorectal Cancer Cells

“…BCRP, a member of the ABCG half-transporter subfamily [23], has a drug resistance profile similar though not identical to P-gP. In this way, various studies have reported a potential action of RSV to decrease P-gP expression [24] and subsequently to enhance the activity of various anticancer drugs [25,26,27]. Given the rapid efflux of resveratrol colonic tumor cells, the question may arise whether the main metabolites of resveratrol are supported or not by the latter or if only the aglycone molecule is concerned.…”