Effect of curcumin on human colon cancer multidrug resistance in vitro and in vivo

Abstract

OBJECTIVE:To determine whether curcumin reverses the multidrug resistance of human colon cancer cells in vitro and in vivo.METHODS:In a vincristine-resistant cell line of human colon cancer, the cell viability of curcumin-treated cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Rhodamine123 efflux was evaluated to detect P-glycoprotein transporter activity, and expression of the multidrug resistance protein 1 and survivin genes was analyzed by reverse transcription polymerase chain reaction and western blotting. In addition, xenograft mouse tumors were grown and treated with curcumin. The morphology of the xenografts was investigated by hematoxylin-eosin staining. The in vivo expression of the multidrug resistance gene and P-glycoprotein and survivin genes and proteins was observed using reverse transcription-polymerase chain reaction and western blotting, respectively.RESULTS:Curcumin was not obviously toxic to the vincristine-resistant human colon cancer cells at concentrations less than 25 μM, but the growth of cells was significantly inhibited. At concentrations greater than 25 μM, curcumin was toxic in a concentration-dependent manner. The sensitivity of cells to vincristine, cisplatin, fluorouracil, and hydroxycamptothecin was enhanced, intracellular Rhodamine123 accumulation was increased (p<0.05), and the expression of the multidrug resistance gene and P-glycoprotein were significantly suppressed (p<0.05). The combination of curcumin and vincristine significantly inhibited xenograft growth. The expression of the multidrug resistance protein 1 and survivin genes was significantly reduced in xenografts of curcumin-treated mice and mice treated with both curcumin and vincristine relative to control mice.CONCLUSION:Curcumin has strong reversal effects on the multidrug resistance of human colon carcinoma in vitro and in vivo.

Curcumin inhibits PhIP induced cytotoxicity in breast epithelial cells through multiple molecular targets

“…Curcumin inhibits cell proliferation and has anticancer effects [19]. Recently, several researchers have demonstrated the anticancer effect of curcumin in prostate [20,21], breast [22][23][24][25], colon [26][27][28], and liver cancer [29]. Thus, curcumin has gained interest as a dietary supplement because there is substantial evidence in preclinical models that curcumin is a potent chemopreventive dietary agent [30][31][32].…”

Synthetic Analogs of Curcumin Modulate the Function of Multidrug Resistance–Linked ATP-Binding Cassette Transporter ABCG2

“…Curcumin is a natural product and a dietary constituent of turmeric (Ammon and Wahl, 1991). It is a well studied phytochemical that has the potential to suppress the growth of many cancer cell lines (Sa and Das, 2008;Lu et al, 2013). It has been shown that curcumin and its metabolites or constituents reverse the drug resistance in cells expressed by ABCB1, ABCC1, and especially ABCG2 (Anuchapreeda et al, 2002;Chearwae et al, 2004Chearwae et al, , 2006a.…”

Curcumin is a tight-binding inhibitor of the most efficient human daunorubicin reductase – Carbonyl reductase 1

“…Since anthracyclines like DAUN and DOX are substrates for P-gp (P-glycoprotein 1 or ABCB1) [52] some cancer cells express large amounts of P-gp, which would gain anthracycline related resistance [53,54]. Interestingly, it has been demonstrated that curcumin not only interacts directly with the drug binding site of the ABCB1-transporter [55,56] but also the expression of the multidrug resistance gene and ABCB1-transporter (protein) was significantly suppressed in both, in vitro and in vivo, respectively [57]. In summary, the effects of curcumin depend on both, the upregulation of anthracycline reductases and the inhibition of ABC-transporters and reductases.…”