Abstract 2039: Cordycepin inhibits breast cancer migration and invasion by targeting epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs)

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Abstract Cancer metastasis is one of the major causes of human death. The developmental stage epithelial to mesenchymal transition (EMT) is associated with cancer metastasis. Cordycepin (CD) is a natural compound, found in traditionally used medicinal mushroom Cordyceps. In this study, we have investigated the anticancer and antimetastatic activity of CD, and whether this compound regulates epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs). By employing cell viability assay and real-time cell analysis in BT549, 4T1 and MDA-MB-435 cell lines, we found that CD can potentially inhibit cancer cell growth, migration and invasion. By using quantitative PCR (qPCR) and Western blot analysis, we also studied the expression of EMT associated proteins N-Cadherin and E-Cadherin, and their transcription factors TWIST1, SNAIL1, SLUG and ZEB1 in BT549 and 4T1 cell lines. By dual-luciferase reporter assay, we confirmed that CD is able to inactivate EMT signaling pathway with mediatory of TWIST1 and SLUG. CD treatment also inhibited the growth and metastasis of cancer cell-derived xenograft tumors in mouse model. Taken together, CD inhibits breast cancer cell migration and invasion by targets EMT-TFs, which might be a possible CD mechanism of antimetastatic action. In addition, CD derivatives by conjugating thymoquinone, a promising anti-cancer compound from nature, were designed to investigate whether there are dramatically improvements on their antimetastatic activities. In conclusion, this study suggests CD as a potential anticancer and antimetastatic molecule, which might be a promising therapeutic agent against breast cancer. Funding: This work was supported by the NSFC (81172049, 81672887). Citation Format: Junjiang Fu, Chunli Wei, Jingliang Cheng, Md. Asaduzzaman Khan, Lisha Yang, Hui Zou. Cordycepin inhibits breast cancer migration and invasion by targeting epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2039.