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

• Main Authors: Chatla Srinivas, M Janaki Ramaiah, A Lavanya, Suresh Yerramsetty, P B Kavi Kishor, Shaik Anver Basha, Ahmed Kamal, Utpal Bhadra, Manika-Pal Bhadra
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2015-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC4638343?pdf=render

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-4β-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.