Journal of Microbial & Biochemical Technology

Identification of active compounds for the development of new anti-prostate cancer drugs : Comparative study in yeast and human cells

Joint Event on 4^th World Congress and Expo on Applied Microbiology & 2^nd International Conference on Food Microbiology

November 29-December 01, 2017 Madrid, Spain

Sergio Giannattasio, Nicoletta Guaragnella, Luna Laera and Loredana Moro

Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies - CNR, Italy

Scientific Tracks Abstracts: J Microb Biochem Technol

Abstract:

More than 70% of prostate cancer (PCa) patients display loss or reduction of BRCA2 protein, an onco-suppressor involved in DNA repair through homologous recombination. We have shown that loss of BRCA2 confers cells resistance to anoikis, a peculiar form of programmed cell death (PCD) necessary for cancer cells to colonize distal sites during the metastatic process. This PCD-promoting function of BRCA2 is conserved in the yeast Saccharomyces cerevisiae. Patients with metastatic PCa display only temporary disease control following androgen deprivation but they eventually develop disease progression to virtually incurable castration-resistant prostate cancer (CRPC). We used yeast expressing BRCA2, normal prostate cell and a CRPC cell line model for a pre-clinical toxicity screening of 6-thioguanine (6-TG) and six 6-TG analogues. We found that 6-TG decreased proliferation in yeast preferably in the presence of BRCA2 and normal prostate cells without inducing cell death. Strikingly, 6-TG not only impaired cell proliferation but also induced significant cell death in CRPC cells by activating a PCD program. Silencing of BRCA2 expression increased CPRC cell sensitivity to 6-TG-induced cell death. 2,6-dithiopurine (2,6DTP) strongly decreased proliferation and induced cell death in yeast independently of BRCA2. 2,6DTP and 2-amino-6-bromopurine selectively induced PCD in BRCA2-expressing CPRC cells. These results suggest the potential use of 6-TG and its analogues for the treatment of CRPC alone or in combination with taxanes, chemotherapeutic drugs approved for CRPC treatment.

Biography :

Sergio Giannattasio has completed his studies in Chemistry from Universtity of Bari, Italy in 1982. He is Senior Scientist at the Institute of Biomebranes, Bioenergetics and Molecular Biotechnlogies of CNR in Bari. In 2014 he has been awarded with the qualification as Full Professor in Applied Biology. He has published 66 papers in reputed JCR journals with 1586 citations and h-index 24 (Google Scholar) and has been serving as an Editorial Board Member of repute. His research interests include mitochondria-to-nucleus cross-talk in cell stress response and the role in tumorigenesis of onco-suppressor BRCA2 using yeast Saccharomyces cerevisiae as a model.