BOCCO JOSE LUIS
Congresos y reuniones científicas
Título:
Natural Products as a Source of Novel Synthetic Lethality Inducers in BRCA-Deficient Cancer Cells
Autor/es:
PANSA M. F.; PACCIARONI A.; GARCÍA M.E.; OBERTI J. C.; CARBAJOSA S.; CAMPODÓNICO P.B; PAVIOLO N.S.; BARBOZA G. E.; GOTTIFREDI V.; BOCCO J.L.; NICOTRA V. E. ; SORIA G.
Lugar:
Buenos Aires
Reunión:
Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
Induction of synthetic lethality (SL) is a precision strategy which takes advantage of tumor mutations to induce selective tumor death.A high incidence type of breast and ovarian cancers are characterized by BRCA1/2 germline mutations, which can thus be used as a genetic background to screen for SL inducers. Natural products provide a vast source of compounds for drug development due to their great chemical diversity. Thus, the aim of this work was to search for synthetic lethality inducers in a library of plant extracts and pure compounds from Argentina. We used a cell-based screening platform that compares BRCA1/2 deficient with proficient cells. In this platform the three cells populations are co-cultured and simultaneously exposed to the plant extracts and pure compounds. Cell survival is calculated considering the ratio of BRCA-proficient and BRCA-deficient populations at the end of the experiment. We found one family of pure compounds that triggers SL in BRCA2-deficient cells and one active alkaline extract with SL activity against BRCA1-deficient cells. To identify the active/s compound/s in this extract we perform bio-guided fractionation using VLC and Sephadex chromatography. We found 3 members of the furoquinoline family of alkaloids as the most active compounds.