Isorhapontigenin shows strong anti-melanoma cell activity, and induces anti-tumor immunity
| Autor: | Yinhong Song, Zouzou Yu, Chenxi Tong, Mei Liu, Xiaoling Jiang, Yan Zeng, Changrong Chen |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 202:136.12-136.12 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Background Melanoma is one of the deadliest forms of skin cancer, and its incidence has continued to rise during the past decade. Isorhapontigenin (ISO) is a new derivative of stilbene compound, isolated from Chinese herb Gnetum Cleistostachyum with capability of antitumor. Purpose The potential anti-melanoma activity, impact on genes’ expression, as well as the influence of immune response against melanoma of ISO were detected in our studies in order to clarify its anti-melanoma effect and the corresponding mechanism. Methods Cytotoxicity of ISO on melanoma cell line B16F10 was studied by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell cycle analysis by flow cytometry, annexin V staining, RT-qPCR and Western blot were used to elucidate the mechanism of action of ISO at the cellular level. The in vivo anti-tumor ability of ISO was measured in C57BL/6 mouse syngraft models. Results ISO induced dose-dependent inhibitory effect on the proliferation of B16F10 cell by arresting cells at G0/G1 phase promoting the apoptosis of the cell, which was associated with an increase in the Bax:Bcl-2 ratio and decrease in the proliferative-related genes CYCLIN D1 and SURVIVIN in vitro. In addition, ISO could inhibit the tumor immune escape by promoting the expression of MHC molecules on the membrane of tumor cells, and decreased the infiltration of Tregs and MDSCs which involved in suppressing the anti-tumor effects of immune system. On the other hand, ISO increased the infiltration of T cells, NK cells and NKT cells, which was able to enhance the anti-tumor immune response. Conclusion Taken together, these findings indicate that ISO may be useful as a treatment for Melanoma and thus warrants further investigation. |
| Databáze: | OpenAIRE |
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