Accession Number:

ADA612725

Title:

Monoamine Oxidase A: A Novel Target for Progression and Metastasis of Prostate Cancer

Descriptive Note:

Annual rept. 30 Sep 2013-29 Sep 2014

Corporate Author:

UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES

Personal Author(s):

Report Date:

2014-10-01

Pagination or Media Count:

19.0

Abstract:

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.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE