Phytochemicals: Potential Lead Molecules for MDR Reversal

Abstract

Multidrug resistance (MDR) is one of the main impediments in the treatment of cancers. MDR cancer cells are resistant to multiple anticancer drugs. One of the major mechanisms of MDR is the efflux of anticancer drugs by ABC transporters. Increased activity and overexpression of these transporters are important causes of drug efflux and, therefore, resistance to cancer chemotherapy. Overcoming MDR is a fundamental prerequisite for developing an efficient treatment of cancer. To date, various types of ABC transporter inhibitors have been employed but no effective anticancer drug is available at present, which can completely overcome MDR. Phytochemicals can reverse MDR in cancer cells via affecting the expression or activity of ABC transporters, and also through exerting synergistic interactions with anticancer drugs by addressing additional molecular targets. We have listed numerous phytochemicals which can affect the expression and activity of ABC transporters in MDR cancer cell lines. Phytochemicals in the groups of flavonoids, alkaloids, terpenes, carotenoids, stilbenoids, lignans, polyketides, and curcuminoids have been examined for MDR-reversing activity. The use of MDR-reversing phytochemicals with low toxicity to human in combination with effective anticancer agents may result in successful treatment of chemotherapy-resistant cancer. In this review, we summarize and discuss published evidence for natural products with MDR modulation abilities.

Design and Synthesis of Multi-Functional Superparamagnetic Core-Gold Shell Nanoparticles Coated with Chitosan and Folate for Targeted Antitumor Therapy

“…Doxorubicin (DOX) is one of the most efficient anti-cancer substances and is extensively used to treat breast cancer and other malignancies such as bladder, ovarian, and lung cancer [ 4 , 5 ]. However, its clinical use is limited due to its dose-dependent cell toxicity (myelosuppression and cardiotoxicity), multidrug resistance development, and low specificity against cancer cells [ 6 , 7 ]. Current research progress on nanotechnology has led to the development of nanocarrier-drug delivery vehicles and their potential applications in gene delivery and cancer therapy [ 8 , 9 , 10 ].…”

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

“…Schisandrin A (Deoxyschizandrin), isolated from Fructus Schizandrae, reversed P-gp-mediated DOX resistance in MCF-7/DOX cells by blocking P-gp, NF-κB, and Stat3 signaling [123]. Moreover, tanshinone microemulsion can significantly reverse drug resistance of K562/ADM cells by inhibiting the P-gp efflux pump effect and increasing the intracellular concentration of chemotherapeutic drugs [124]. Honokiol and magnolol are the main active ingredients in Magnolia officinali.…”

Activity of Cordycepin From Cordyceps sinensis Against Drug-Resistant Tumor Cells as Determined by Gene Expression and Drug Sensitivity Profiling

“…21,[34][35][36] Forty-nine ABC transporters, subdivided into 7 separate families (A-G) based on sequence homology, have been described in humans, 37,38 among which particularly P-gp, multidrug resistance-related protein (MRP1) and breast cancer resistance protein (BCRP) have been widely studied. 39,40 As a newer ABC transporter, ABCB5 was also found to be expressed in stem-like cancer cells and other types of tumors conferring MDR, and it was shown to be related to clinical treatment response of tumors in cancer patients. [41][42][43][44][45] Although great attempts are being made to either discover or design efficient and selective ABC transporter modulators, clinical trials have not yet been successful due to unpredictable side effects, and MDR modulators have not entered clinical routine oncology.…”