Curcumin as a Modulator of P-Glycoprotein in Cancer: Challenges and Perspectives

Abstract

Multidrug resistance (MDR) presents a serious challenge to the efficiency of cancer treatment, and may be associated with the overexpression of drug efflux pumps. P-glycoprotein (P-gp) is a drug efflux pump often found overexpressed in cases of acquired MDR. Nevertheless, there are no P-gp inhibitors being used in the current clinical practice, due to toxicity problems, drug interactions, or pharmacokinetic issues. Therefore, it is important to identify novel inhibitors of P-gp activity or expression. Curcumin is a secondary metabolite isolated from the turmeric of Curcuma longa L. which has been associated with several biological activities, particularly P-gp modulatory activity (by inhibiting both P-gp function and expression). However, curcumin shows extensive metabolism and instability, which has justified the recent and intensive search for analogs of curcumin that maintain the P-gp modulatory activity but have enhanced stability. This review summarizes and compares the effects of curcumin and several curcumin analogs on P-glycoprotein function and expression, emphasizing the potential of these molecules for the possible development of safe and effective inhibitors of P-gp to overcome MDR in human cancer.

Insights into the effects of the endocannabinoid system in cancer: a review

“…Tumours become resistant to a great number of different drugs without structural or functional similarities, including anthracyclines, taxanes and Vinca alkaloids, and this hampers cancer treatments (An et al, ). Much of such resistance to cancer chemotherapy involves the multidrug resistance protein 1 (MDR1), an efflux pump that belongs to the family of ATP‐binding cassette transporters (ABC) (Lopes‐Rodrigues et al, ) and other proteins of the ABC superfamily such as the breast cancer resistance protein (ABCP or ABCG2) (Chen et al, ). Several studies have reported the involvement of the ECS in the mediation of resistance to anticancer drugs.…”

Cytotoxicity, Cell Cycle Arrest, and Apoptosis Induction Activity of Ethyl-p-methoxycinnamate in Cholangiocarcinoma Cell

“…Several anticancer agents derived from medicinal plants fail for treatment because it is the substrate of P-glycoprotein and the situation becomes worse if the compound can induce mdr-1 gene expression (Barthomeuf et al, 2005;Lopes-Rodrigues et al, 2016). Results of the study showed that even CL-6 and Caco-2 have different EPMC sensitivity, but it does not effect on mdr-1 expression in both cell lines.…”

An update on Chinese herbal medicines as adjuvant treatment of anticancer therapeutics

“…ototoxicity, nephrotoxicity and neurotoxicity) (57). Curcumin might be a safe and effective inhibitor of P-glycoprotein (P-gp) to overcome multidrug resistance (MDR) in human cancer (58). In addition, some research has revealed that curcumin can sensitize tumors to different chemotherapeutic agents including doxorubicin, 5-FU, paclitaxel, vincristine, oxaliplatin, etoposide and so on in numerous cancers (e.g., breast,colon, pancreas, gastric, liver, blood, lung, prostate, and ovary) (59).…”