Enhancing Anticancer Drug Activity in Multidrug Resistant Tumors by Modulating P-Glycoprotein with Dietary Nutraceuticals

Cancer is one of the most virulent, devastating and deadliest disease in the world and it represents the second leading cause of death worldwide (Jemal et al., 2008; Siegel et al., 2012), with approximately 14 million new cases and 8.2 million cancer related deaths in 2012 (Ferlay et al., 2015). Chemotherapy is one of the most effective treatments for metastatic cancers (Chang, 2010). Multidrug resistance (MDR) is one of the major obstacles in the successful chemotherapy of various cancers (Baguley, 2010; Eid et al., 2012; Xu et al., 2012; Kibria et al., 2014; Liu et al., 2014). It is widely accepted now that MDR exists against every effective drug (Callaghan et al., 2014). Therefore, the modulation of cellular molecules involved in MDR and circumvent drug resistance is likely to improve chemotherapy (Gottesman et al., 2002; Gillet et al., 2010). P-glycoprotein, a 170 kDa transmembrane phosphorylated glycoprotein encoded by MDR1 (ABCB1), belongs to ATP-binding cassette (ABC) superfamily of membrane transporters (Eichhorn and Efferth, 2012; Eid et al., 2012). It is composed of 1280 amino acids and consists of two similar halves each containing six transmembrane domains and one ATP binding domain (Nabekura, 2010a; Zeino et al., 2015). P-gp was first discovered in 1976 in Chinese hamster ovary (CHO) cells, where it was found to display resistance to anticancer drugs (Callaghan et al., 2014). By the 1980s antibodies had been developed to p-gp to detect the distribution and expression of this