A synthetic cantharidin analog for the enhancement of doxorubicin suppression of stem cell-derived aggressive sarcoma

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• 作者：Chao Zhang ; Yi Peng ; Fengchao Wang ; Xu Tan ; Nan Liu ; Song Fan ; Dechun Wang ; Lilong Zhang ; Dengqun Liu ; Tao Wang ; Shaojun Wang ; Yue Zhou ; Yongping Su ; Tianmin Cheng ; Zhengping Zhuang ; Chunmeng Shi
• 关键词：Cantharidin derivative ; PP2A inhibitor ; Doxorubicin ; Sarcoma ; Metastasis ; Enhanced chemotherapy
• 刊名：Biomaterials
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：31
• 期：36
• 页码：9535-9543
• 全文大小：2345 K

文摘

Failure to cure many cancers once they are disseminated has been attributed to the presence of resistant cancer stem cells. Cantharidin, a natural compound isolated from the beetles and other insects has been traditionally used as anticancer agent, but limited by its significant toxicity. It has shown that cantharidin can force cancer cells prematurely into cell cycle and subsequently induce apoptotic cell death through the inhibition of protein phosphatase 2A (PP2A). In this study, we showed that a synthesized analog of cantharidin, LB1, with significant PP2A inhibition activity but without apparent toxicity, greatly enhanced the effectiveness of the standard anti-sarcoma chemotherapeutic agent, doxorubicin (DOX), in the xenograft growth inhibition and lung metastases prevention of an aggressive sarcoma derived from transformed mesenchymal stem cells in syngeneic rats. We report here on the possibility of, pharmacologic inhibition of PP2A with low toxicity cantharidin derivatives may be a useful strategy to enhance the effectiveness of DNA-damaged chemotherapeutic drugs against stem cell-derived cancer.