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Anti-tumorigenicity of dietary ?-mangostin in an HT-29 colon cell xenograft model and the tissue distribution of xanthones and their phase II metabolites.

ABSTRACT: This study investigated the in vivo and in vitro activity of ?-mangostin (?-MG), the most abundant xanthone in mangosteen pericarp, on HT-29 cell tumorigenicity, proliferation, and several markers of tumor cell activity, as well as the profile and amounts of xanthones in serum, tumor, liver, and feces.Balb/c nu/nu mice were fed either control diet or diet containing 900 mg ?-MG/kg. After 1 week of acclimation to diet, mice were injected subcutaneously with HT-29 cells and fed the same diets ad libitum for an additional 2 or 4 weeks. After 2 and 4 weeks, tumor mass and the concentrations of BcL-2 and ?-catenin in tumors of mice fed diet with ?-MG were significantly less than in mice fed control diet. Xanthones and their metabolites were identified in serum, tumor, liver, and feces. In vitro treatment of HT-29 cells with ?-MG also inhibited cell proliferation and decreased expression of BcL-2 and ?-catenin.Our data demonstrate that the anti-neoplastic effect of dietary ?-MG is associated with the presence of xanthones in the tumor tissue. Further investigation of the impact of beverages and food products containing xanthones on the prevention of colon cancer or as complementary therapy is merited.

SUBMITTER: Chitchumroonchokchai C

PROVIDER: S-EPMC3886125 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Anti-tumorigenicity of dietary α-mangostin in an HT-29 colon cell xenograft model and the tissue distribution of xanthones and their phase II metabolites.

Chitchumroonchokchai Chureeporn C Thomas-Ahner Jennifer M JM Li Jie J Riedl Kenneth M KM Nontakham Jannarin J Suksumrarn Sunit S Clinton Steven K SK Kinghorn A Douglas AD Failla Mark L ML

Molecular nutrition & food research 20121213 2

<h4>Scope</h4>This study investigated the in vivo and in vitro activity of α-mangostin (α-MG), the most abundant xanthone in mangosteen pericarp, on HT-29 cell tumorigenicity, proliferation, and several markers of tumor cell activity, as well as the profile and amounts of xanthones in serum, tumor, liver, and feces.<h4>Methods and results</h4>Balb/c nu/nu mice were fed either control diet or diet containing 900 mg α-MG/kg. After 1 week of acclimation to diet, mice were injected subcutaneously wi ...[more]

PMID: 23239542

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Project description:In the present study, we evaluated the antitumor effect of two synthetic analogs of vitamin D, namely PRI-2191 [(24R)-1,24-dihydroxyvitamin D3] and PRI-2205 (5,6-trans calcipotriol), in combined human colon HT-29 cancer treatment with 5-fluorouracil (5-FU). Mice bearing HT-29 tumors transplanted subcutaneously or orthotopically were injected with vitamin D analogs and 5-FU in various schedules. A statistically significant inhibition of subcutaneous or orthotopic tumor growth was observed as a result of combined therapy. In HT-29 tumors and in cells from in vitro culture, we observed increased vitamin D receptor (VDR) expression after treatment with either PRI-2205 or 5-FU alone, or in combination. Moreover, PRI-2205 decreased the percentage of cells from intestinal tumors in G2/M and S stages and increased sub-G1. Increased VDR expression was also observed after combined treatment of mice with 5-FU and PRI-2191. Moreover, our docking studies showed that PRI-2205 has stronger affinity for VDR, DBP and CAR/RXR ligand binding domains than PRI-2191. PRI-2191 analog, used with 5-FU, increased the percentage of subcutaneous tumor cells in G0/G1 and decreased the percentage in G2/M, S and sub-G1 populations as compared to 5-FU alone. In in vitro studies, we observed increased expression of p21 and p-ERK1/2 diminution via use of both analogs as compared to use of 5-FU alone. Simultaneously, PRI-2191 antagonizes some pro-apoptotic activities of 5-FU in vitro. However, in spite of these disadvantageous effects in terms of apoptosis, the therapeutic effect expressed as tumor growth retardation by PRI-2191 is significant. Our results suggest that the mechanism of potentiation of 5-FU antitumor action by both analogs is realized via increased p21 expression and decreased p-ERK1/2 level which may lead to diminution of thymidylate synthase expression. Higher binding affinity for VDR, DBP, but also for CAR\RXR ligand binding domain of PRI-2205 may, in part, explain its very low toxicity with sustained anticancer activity.

Dataset Information

Anti-tumorigenicity of dietary ?-mangostin in an HT-29 colon cell xenograft model and the tissue distribution of xanthones and their phase II metabolites.

Publications

Anti-tumorigenicity of dietary α-mangostin in an HT-29 colon cell xenograft model and the tissue distribution of xanthones and their phase II metabolites.

Similar Datasets

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