OT-404, multi-targeted anti-cancer agent affecting tumor proliferation, chemo-resistance, and angiogenesis.
There is a need for a comprehensive anti-cancer strategy that simultaneously targets abnormal proliferation, angiogenesis rates, and development of chemotherapy resistance. We have identified a small molecule, OT-404, that effectively inhibited proliferation and angiogenesis of either chemo-sensitive or -resistant human cancer cells and enhanced cancer cell sensitivity to different chemotherapy. In vivo studies of human tumor xenografts in nude mice showed that OT-404, used alone or encapsulated into nanoparticles, inhibited the growth of doxorubicin-resistant breast cancer MCF-7 by more than 80%, and by 95% when combined with doxorubicin. These findings provide evidence for the potential of OT-404 in cancer management.
Department of Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
Abdelhadi
A
Rebbaa
Ghanshyam
G
Patil
Murat
M
Yalcin
Thangirala
T
Sudha
Shaker A
SA
Mousa
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053769:Nanocapsules; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D020298:U937 Cells; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D053769:Nanocapsules; D004317:Doxorubicin