curcumin and limonin

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.

Topics: Abietanes; Alkaloids; Allyl Compounds; Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; Benzodioxoles; beta Carotene; Biflavonoids; Capsaicin; Catechin; Catechols; Curcumin; Dietary Supplements; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Fatty Alcohols; Furocoumarins; Humans; Indoles; Limonins; Neoplasms; Phytotherapy; Piperidines; Polyunsaturated Alkamides; Proanthocyanidins; Quercetin; Resveratrol; Stilbenes; Sulfides; Tea; Triterpenes; Xanthophylls

Phytochemicals may reduce chronic inflammation and cancer risk in part by modulating T-cell nuclear factor-kappaB (NF-kappaB) activation. Therefore, we examined the effects of curcumin (Cur) and limonin (Lim) feeding on NF-kappaB-dependent CD4(+) T-cell proliferation. DO11.10 transgenic mice (n = 5-7) were fed diets containing 1% Cur or 0.02% Lim combined with either (n-6) PUFA [5% corn oil (CO)] or (n-3) PUFA [4% fish oil+1% corn oil (FO)] for 2 wk, followed by splenic CD4(+) T-cell isolation and stimulation with ovalbumin peptide 323-339 (OVA) and antigen-presenting cells from mice fed a conventional nonpurified rodent diet. Both Cur and Lim diets suppressed (P < 0.05) NF-kappaB p65 nuclear translocation in activated CD4(+) T-cells. In contrast, activator protein-1 (c-Jun) and nuclear factor of activated T-cells c1 were not affected compared with the CO control diet (no Cur or Lim). CD4(+) T-cell proliferation in response to either mitogenic anti-CD3/28 monoclonal antibodies (mAb) or antigenic stimulation by OVA was also suppressed (P < 0.05) by Cur as assessed by carboxyfluorescein succinimidyl ester staining. In contrast, interleukin-2 production was not directly associated with NF-kappaB status. Interestingly, dietary combination with FO enhanced the suppressive effects (P < 0.05) of Cur or Lim with respect to CD4(+) T-cell proliferation in response to anti-CD3/28 mAb. These results suggest that combination chemotherapy (FO+Cur or Lim) may favorably modulate CD4(+) T-cell-mediated inflammation.

Topics: Animals; Antibodies, Monoclonal; Antigen-Presenting Cells; CD28 Antigens; CD3 Complex; CD4-Positive T-Lymphocytes; Cell Division; Corn Oil; Curcumin; Diet; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fish Oils; Interleukin-2; Limonins; Mice; Mice, Inbred BALB C; Mice, Transgenic; NF-kappa B; Ovalbumin; Peptide Fragments