mangostin and Carcinoma--Squamous-Cell

Mangosteen (Garcinia mangostana) is a tree found in South-East Asia and the pericarp of its fruit has been used in folk medicine for the treatment of many human illnesses. Mangosteen fruit rinds contain a high concentration of xanthone, which is a type of polyphenol. One type of xanthone, α-mangostin, has been reported to exert chemopreventive effects against chemically-induced colon cancer through the decrease of c-Myc expression, suppressing tumor growth in a mouse model of mammary cancer. A recent study demonstrated the inhibitive effect of α-mangostin on the growth of prostate cancer. However, it remains unclear whether α-mangostin induces cell death in oral cancer. The present study examined the impact of α-mangostin on human oral squamous cell carcinoma (HOSCC). Firstly we analyzed the expression of c-Myc in five HOSCC cell lines. The highest expression level of c-Myc mRNA was observed in SAS cells and the lowest in HSC-4 cells. Therefore, SAS cells were treated with α-mangostin, which was found to exert a weak cytocidal effect. Since α-mangostin has been reported to exert synergistic effects on cancers when combined with anticancer drugs, we attempted to evaluate such synergistic effects of α-mangostin when used with a cytokine, tumor necrosis factor (TNF)-related apoptosis‑inducing ligand (TRAIL). We found that the combination of α-mangostin with TRAIL induced apoptosis of SAS cells through the mitochondrial pathway via activation of caspase-9 and -3/7, following release of cytochrome c. This apoptosis was induced by S/G2/M-phase arrest. Immunopositivity for c-Myc was observed in the cytoplasm of tumor cells in 16 (40%) of the 40 cases of HOSCC. These data revealed that the combination of α-mangostin and TRAIL may have a considerable potential for the treatment of oral cancer.

Topics: Animals; Apoptosis; Carcinoma, Squamous Cell; Caspases; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Garcinia mangostana; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mouth Neoplasms; Plant Extracts; Proto-Oncogene Proteins c-myc; TNF-Related Apoptosis-Inducing Ligand; Xanthones

The purpose of this study was to investigate the effect of alpha-mangostin on matrix metalloproteinase (MMP)-2 and MMP-9 expression in head and neck squamous cell carcinoma (HNSCC). The human HNSCC cell lines were treated with alpha-mangostin and the cytotoxicity of alpha-mangostin in HNSCC was determined using the MTS assay. To determine the effect of alpha-mangostin on the expression of MMP-2 and MMP-9 in HNSCC, gelatin zymography and RT-PCR were performed. The results showed that alpha-mangostin increased in growth inhibition of HNSCC cell lines in a concentration-dependent manner. Treatment with alpha-mangostin decreased MMP-2 and MMP-9 expression in a concentration-dependent manner in all cell lines. These findings suggested that alpha-mangostin might be a potential therapeutic agent for HNSCC.

Topics: Base Sequence; Carcinoma, Squamous Cell; Cell Line; DNA Primers; Head and Neck Neoplasms; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Reverse Transcriptase Polymerase Chain Reaction; Xanthones

This study aimed at investigating the anti-invasive activities of α-mangostin on human melanoma SK-MEL-28 and squamous cell carcinoma A-431 cell lines.. Cytotoxicity was tested by the crystal violet assay; anti-invasive activity was detected by the wound healing, cell-matrix adhesion, and boyden chamber assays; and gene regulatory effects by qRT-PCR. Treatments were at non-toxic concentrations (0-1.25 μg/ml for A-431 cells and 0-2.5 μg/ml for SK-MEL-28 cells).. α-Mangostin inhibited motility, adhesion, migration and invasion. Invasive ability was reduced to 4% and 20% following α-mangostin treatment compared with untreated A-431 and SK-MEL-28 cells, respectively. Inhibition of gene expression of MMP-2, MMP-9, NF-κB, and Akt1 was involved in the anti-invasive activities on A-431 cells. Inhibition of MMP-2, NF-κB and IκBα was involved for SK-MEL-28 cells.. α-Mangostin suppressed the metastatic processes of SK-MEL-28 and A-431 cell lines by differentially regulating metastasis-related genes, showing potential as an anti-metastatic agent.

Topics: Carcinoma, Squamous Cell; Cell Adhesion; Cell Line, Tumor; Cell Movement; Garcinia mangostana; Gene Expression; Humans; Melanoma; Neoplasm Invasiveness; Neoplasm Metastasis; Plant Extracts; Skin Neoplasms; Xanthones

The purposes of this study were to measure the cytotoxic effect of alpha-mangostin on head and neck squamous cell carcinoma (HNSCC) cell lines, to evaluate the apoptotic aspect of dead cells, and to identify the molecular mechanism involved in apoptosis.. The human HNSCC cell lines HN-22, HN-30 and HN-31 were treated with alpha-mangostin. The apoptotic effects of alpha-mangostin on HNSCC cells were determined by observation the morphological changes of cells, immunofluorescence for single-stranded DNA (ssDNA), and DNA fragmentation analysis. The expression of bax, bcl-2, and p53 were detected by RT-PCR and Western blot analysis.. Alpha-mangostin showed excellent apoptotic effects on HNSCC cell lines, which induced the down-regulation of bcl-2, but up-regulation of bax and p53 in HN-22, HN-30 and HN-31.. The present study suggests that the induction of apoptosis by alpha-mangostin seemed to be modulated by bcl-2, bax and p53 level in HNSCC cell lines.

Topics: Analysis of Variance; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Bcl-2-Like Protein 11; Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; DNA Fragmentation; DNA-Binding Proteins; Head and Neck Neoplasms; Humans; Membrane Proteins; Proto-Oncogene Proteins; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured; Xanthones