Synergism between α-mangostin and TRAIL induces apoptosis in squamous cell carcinoma of the oral cavity through the mitochondrial pathway
Autor: | Masakatsu Fukuda, Yusuke Komine, Hiroyasu Hayashi, Hide Sakashita, Fuyoko Taira, Junya Shiono, Hideaki Sakashita, Genki Miyake |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Cancer Research Programmed cell death food.ingredient medicine.medical_treatment Xanthones Apoptosis Biology Garcinia mangostana Proto-Oncogene Proteins c-myc TNF-Related Apoptosis-Inducing Ligand 03 medical and health sciences Mice 0302 clinical medicine food Cell Line Tumor medicine Animals Humans Cell Proliferation Oncogene Plant Extracts Cancer General Medicine Cell Cycle Checkpoints Cell cycle medicine.disease Gene Expression Regulation Neoplastic 030104 developmental biology Cytokine Oncology 030220 oncology & carcinogenesis Caspases Cancer research Carcinoma Squamous Cell Tumor necrosis factor alpha Mouth Neoplasms |
Zdroj: | Oncology reports. 38(6) |
ISSN: | 1791-2431 |
Popis: | 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. |
Databáze: | OpenAIRE |
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