Novel Etoposide Analogue Modulates Expression of Angiogenesis Associated microRNAs and Regulates Cell Proliferation by Targeting STAT3 in Breast Cancer

作者：Srinivas Chatla; Ramaiah M Janaki; Lavanya A; Yerramsetty Suresh; Kishor P B Kavi; Basha Shaik Anver; Kamal Ahmed; Bhadra Utpal; Bhadra Manika Pal^*

来源：PLos One, 2015, 10(11): e0142006.

DOI：10.1371/journal.pone.0142006

Tumor microenvironment play role in angiogenesis and carcinogenesis. Etoposide, a known topoisomerase II inhibitor induces DNA damage resulting in cell cycle arrest. We developed a novel Etoposide analogue, Quinazolino-4 beta-amidopodophyllotoxin (C-10) that show better efficacy in regulating cell proliferation and angiogenesis. We evaluated its role on expression of microRNAs-15, 16, 17 and 221 and its targets Bcl-2, STAT3 and VEGF that dictate cell proliferation and angiogenesis. Docking studies clearly demonstrated the binding of Etoposide and C-10 to STAT3. We conclude that combination of Etoposide or C-10 with miR-15, 16, 17 and 221 as a new approach to induce apoptosis and control angiogenesis in breast cancer.

• 出版日期2015-11-9