Monoamine Oxidase A: A Novel Target for Progression and Metastasis of Prostate Cancer
Annual rept. 30 Sep 2013-29 Sep 2014
UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
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The purpose of this project is to investigate the key roles of the monoamine oxidase A MAOA enzyme in the progression and metastasis of prostate cancer PCa. Throughout the Year 2 of this grant we focused our effort on studying the functional and mechanistic roles of MAOA in promoting tumor metastasis to bone. We showed that genetic silencing of MAOA in C4-2 and ARCaPM human PCa lines markedly reduced tumor-invading bone lesions. We also investigated the molecular mechanisms underlying the MAOA functions in PCa by defining its roles in converging reactive oxygen species production and augmentation of HIF1 -mediated signaling. We developed a scalable synthesis of MHI-clorgyline, a novel pharmacological inhibitor of MAOA, which by inhibition of MAOA activity resulted in reduction in expression of oncogenes and cell cycle regulators that promote EMT and cancer cell invasion and migration, suggesting anti-proliferative and anti-metastatic activity of the conjugate.
- Medicine and Medical Research