Yan-Rong Liu1, Bo Sun2, Guo-Hong Zhu3, Wei-Wei Li3, Yi-Xuan Tian3, Lu-Meng Wang3, Shu-Min Zong3, Peng-Zhen Sheng3, Meng Li3, Shuang Chen2, Yuan Qin3, Hui-Juan Liu2, Hong-Gang Zhou3, Tao Sun4, Cheng Yang5. 1. Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China; Drug Safety Evaluation Center, Tianjin International Joint Academy of Biomedicine, Tianjin, China. Electronic address: liuyanrong1984@163.com. 2. Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China. 3. Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology and College of pharmacy, Nankai University, Tianjin, China. 4. Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology and College of pharmacy, Nankai University, Tianjin, China. Electronic address: sunrockmia@hotmail.com. 5. Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology and College of pharmacy, Nankai University, Tianjin, China. Electronic address: cyang66_2001@163.com.
Abstract
BACKGROUND: Selenium supplementation can be used to treat tumors. However, inorganic selenium is highly toxic, and natural organic selenium is extremely rare. Polysaccharides can improve drug bioavailability and targeting. Lentinan is a polysaccharide that has been approved as an anti-cancer drug in Japan and China. METHODS: Lentinan, an antitumor polysaccharide extracted from Lentinus edodes, was conjugated with seleninic acid to be transformed into ester (Se-lentinan) and utilized as drug carrier. The enhancement of the anti-tumor effects of Se-lentinan was evaluated by cell viability, cell cycle, migration, and transwell assays and animal xenograft models. The effects of Se-lentinan on the expression levels of epithelial-mesenchymal transition (EMT) markers were determined through immunofluorescence, Western blot, and immunohistochemistry analyses. RESULTS: Se-lentinan inhibited the invasiveness of B16-BL6 and HCT-8 cells by suppressing EMT. In vivo, Se-lentinan significantly inhibited tumor growth and metastasis of the transplanted melanoma and colon cancer cells and showed less toxicity than sodium selenite. Moreover, Se-lentinan reduced the accumulation of selenium in the liver and kidney tissues of mice and exhibited low organ toxicity. CONCLUSION: The antitumor activity of selenium was enhanced greatly, and its side effects were reduced with the use of lentinan as drug carrier.
BACKGROUND: Selenium supplementation can be used to treat tumors. However, inorganic selenium is highly toxic, and natural organic selenium is extremely rare. Polysaccharides can improve drug bioavailability and targeting. Lentinan is a polysaccharide that has been approved as an anti-cancer drug in Japan and China. METHODS: Lentinan, an antitumor polysaccharide extracted from Lentinus edodes, was conjugated with seleninic acid to be transformed into ester (Se-lentinan) and utilized as drug carrier. The enhancement of the anti-tumor effects of Se-lentinan was evaluated by cell viability, cell cycle, migration, and transwell assays and animal xenograft models. The effects of Se-lentinan on the expression levels of epithelial-mesenchymal transition (EMT) markers were determined through immunofluorescence, Western blot, and immunohistochemistry analyses. RESULTS: Se-lentinan inhibited the invasiveness of B16-BL6 and HCT-8 cells by suppressing EMT. In vivo, Se-lentinan significantly inhibited tumor growth and metastasis of the transplanted melanoma and colon cancer cells and showed less toxicity than sodium selenite. Moreover, Se-lentinan reduced the accumulation of selenium in the liver and kidney tissues of mice and exhibited low organ toxicity. CONCLUSION: The antitumor activity of selenium was enhanced greatly, and its side effects were reduced with the use of lentinan as drug carrier.