title: Novel Etoposide Analogue Modulates Expression of Angiogenesis Associated microRNAs and Regulates Cell Proliferation by Targeting STAT3 in Breast Cancer.
abstract: 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.
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Chatla
authors.initials: C
authors.lastname: Srinivas
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.|School of Chemical and Biotechnology, SASTRA University, Thanjavur, India.
authors.forename: M Janaki
authors.initials: MJ
authors.lastname: Ramaiah
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: A
authors.initials: A
authors.lastname: Lavanya
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Yerramsetty
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, India.
authors.forename: P B
authors.initials: PB
authors.lastname: Kavi Kishor
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Shaik Anver
authors.initials: SA
authors.lastname: Basha
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.affiliation: Functional Genomics and Gene Silencing Group, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: Utpal
authors.initials: U
authors.lastname: Bhadra
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Manika-Pal
authors.initials: MP
authors.lastname: Bhadra
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053453:Caspase 9 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005047:Etoposide / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009389:Neovascularization, Pathologic / Q000473:pathology; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D053453:Caspase 9; D005047:Etoposide; D035683:MicroRNAs; D011034:Podophyllotoxin; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; C000595707:BCL2 protein, human; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; C524941:MIRN17 microRNA, human; C525709:MIR221, human; C494086:STAT3 protein, human; C467484:VEGFA protein, human; C000608804:quinazolino-4-amidopodophyllotoxin