Study on the role of survivin in the anti-melanoma effect of α-mangostin

• Main Authors: Yi-Chun Hung, 洪儀君
• Other Authors: Chia-che chan
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/w5ywq8

碩士 === 國立中興大學 === 生命科學院碩士在職專班 === 103 === Melanoma, the most devastating form of skin cancer, has been increasing in incidence steadily worldwide for decades, Although early stage melanoma is effectively removed by surgery, metastatic melanoma are difficult to treat and have a low survival rate. Chemotherapies are used to treat advanced melanoma. However, their therapeutic efficacy is limited due to chemoresistance and toxicity. Therefore, new agents with a higher therapeutic efficacy are needed for human melanoma. Xanthones, a group of naturally occurring phenolic compounds, are plentiful in the pericarp of mangosteen (Garcinia mangostana Linn.) and are also found in other plants. Anticancer activity is an important biological activity of xanthones. α-Mangostin, a major xanthone compound, has been shown to inhibit the proliferation of a range of human cancer cells, and also can inhibit the metastasis of some types of cancer cells in vitro and in vivo. This study focuses on the role of survivin in the anti-melanoma effect of α-mangostin. Using human colon cancer cell lines A375.S2 as the cellular model, we found that α-mangostin reduced cell viability and also markedly induced PARP cleavage, suggesting the induction of apoptosis. Additionally, α-mangostin dose- and time-dependently induced down-regulation of survivin. This down-regulation is mainly regulated at the level of transcription, as α-mangostin reduced the levels of both survivin mRNA and survivin promoter activity but failed to rescue survivin expression when proteasome-mediated degradation is abolished. Furthermore, overexpression of survivin significantly rescue A375.S2 cells from α-mangostin-induced repression of colony formation. Taken together, we conclude that survivin down-regulation is a critical mode of action of α-mangostin to induce apoptosis in human melanoma cell lines.