xanthochymol has been researched along with Colonic-Neoplasms* in 2 studies
2 other study(ies) available for xanthochymol and Colonic-Neoplasms
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Growth inhibition of colon cancer cells by polyisoprenylated benzophenones is associated with induction of the endoplasmic reticulum response.
Polyisoprenylated benzophenones derived from Garcinia xanthochymus have cytotoxic activity in vitro and antitumor activity in rodent models, but the mechanism is unknown. The purpose of our study was to examine in parallel molecular pathways that are targeted by 3 Garcinia-derived benzophenones-xanthochymol (X), guttiferone E (GE) and guttiferone H (GH), in 3 human colon cancer cell lines, HCT116, HT29 and SW480. The IC50 concentrations were determined and the cells were then treated with X, GE or GH at their respective IC50 or IC50x2 concentrations. Effects on the cell cycle, mitochondrial membrane potential and apoptosis were assessed by flow cytometry and caspase activation. Changes in gene expression were assessed with Illumina 24 K gene arrays. We found that X, GE and GH induced loss of mitochondrial membrane potential and G1 arrest at their IC50 concentrations and induced caspase activation at IC50 x 2 concentrations. An analysis of the changes in gene expression revealed that with all 3 compounds and all 3 cell lines there was a marked increase in expression of several genes, including XBP1, ATF4 and DDIT3/CHOP, which are components of the endoplasmic reticulum stress response. The DDIT4/REDD1 gene, an inhibitor of the mTOR survival pathway, was also up-regulated. Therefore, X, GE and GH appear to inhibit the growth of human colon cancer cells, at least in part, by activating the endoplasmic reticulum stress response and inhibiting the mTOR cell survival pathway. These combined effects may contribute to the anticancer activity of these novel compounds. Topics: Activating Transcription Factor 4; Apoptosis; Benzophenones; Caspases; Cell Cycle; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; DNA-Binding Proteins; Endoplasmic Reticulum; Garcinia; Gene Expression Regulation, Neoplastic; HCT116 Cells; HT29 Cells; Humans; Inhibitory Concentration 50; Linear Models; Mitochondrial Membranes; Nuclear Proteins; Prenylation; Protein Kinases; Reactive Oxygen Species; Regulatory Factor X Transcription Factors; Signal Transduction; TOR Serine-Threonine Kinases; Transcription Factor CHOP; Transcription Factors; Up-Regulation; X-Box Binding Protein 1 | 2008 |
Cytotoxic activities of xanthochymol and isoxanthochymol substantiated by LC-MS/MS.
The methanol extract of the fruit rinds of Garcinia indica showed potent cytotoxic activity against three human cancer cell lines, colon (COLO-320-DM), breast (MCF-7) and liver (WRL-68), as determined by the MTT assay. Fractionation of the methanol extract into hexane-, chloroform- and ethyl acetate-soluble fractions and evaluation of cytotoxic activity of each of the fractions revealed that the ethyl acetate fraction was the most effective as compared to the two other fractions. Two polyisoprenylated benzophenones, xanthochymol and isoxanthochymol, were isolated from the ethyl acetate fraction. Both xanthochymol and isoxanthochymol as a single pure entity did not turn out to be as effective as the ethyl acetate extract from which they have been isolated. The concentrations of xanthochymol and isoxanthochymol in four different extracts--methanol, hexane, chloroform and ethyl acetate--were determined with the help of LC-MS/MS. On the basis of the LC-MS/MS data, combinations of xanthochymol and isoxanthochymol in different ratios were tested in the MTT assay and were found to be effective. Moreover, it was established from the LC-MS/MS data that the combination of xanthochymol and isoxanthochymol in a ratio of 1 : 2 showed maximal cytotoxicity. Topics: Antineoplastic Agents, Phytogenic; Benzophenones; Breast Neoplasms; Cell Line, Tumor; Chromatography, Liquid; Colonic Neoplasms; Garcinia; Humans; Liver Neoplasms; Molecular Structure; Phytotherapy; Tandem Mass Spectrometry | 2007 |