A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells

F Ricci; L Carrassa; M S Christodoulou; D Passarella; B Michel; R Benhida; N Martinet; A Hunyadi; E Ioannou; V Roussis; L Musso; S Dallavalle; R Silvestri; N Westwood; M Mori; C Ingallina; B Botta; E Kavetsou; A Detsi; Z Majer; F Hudecz; S Bosze; B Kaminska; T V Hansen; P Bertrand; C M Athanassopoulos; G Damia

doi:10.2174/1386207321666180124093406

A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells

Comb Chem High Throughput Screen. 2018;21(1):50-56. doi: 10.2174/1386207321666180124093406.

Authors

F Ricci¹, L Carrassa¹, M S Christodoulou², D Passarella², B Michel³, R Benhida³, N Martinet³, A Hunyadi⁴, E Ioannou⁵, V Roussis⁵, L Musso⁶, S Dallavalle⁶, R Silvestri⁷, N Westwood⁸, M Mori⁹, C Ingallina⁷, B Botta⁷, E Kavetsou¹⁰, A Detsi¹⁰, Z Majer¹¹, F Hudecz¹¹, S Bosze¹², B Kaminska¹³, T V Hansen¹⁴, P Bertrand¹⁵, C M Athanassopoulos¹⁶, G Damia¹

Affiliations

¹ IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via Giuseppe La Masa 19, 20156 Milan, Italy.
² Dipartimento di Chimica - Universita degli Studi di Milano - Via C. Golgi 19, 20133 Milan, Italy.
³ Universite Cote d'Azur, CNRS, Institut de Chimie de Nice UMR 7272, 06108 Nice, France.
⁴ Institute of Pharmacognosy, University of Szeged, Eotvos str. 6, 6720 Szeged, Hungary and Interdisciplinary Centre for Natural Products, University of Szeged, Eotvos str. 6, 6720 Szeged, Hungary.
⁵ Department of Pharmacy, Section of Pharmacognosy and Chemistry of Natural Products, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece.
⁶ Department of Food, Environmental and Nutritional Sciences, Universita degli Studi di Milano,Via Celoria 2, 20133 Milan, Italy.
⁷ Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy.
⁸ School of Chemistry and Biomedical Sciences ResearchComplex, University of St Andrews and EaStCHEM, St Andrews KY16, United Kingdom.
⁹ Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, viale Regina Elena 291, 00161 Rome, Italy.
¹⁰ Department of Chemical Sciences, School of Chemical Engineering, National Technical University of Athens Iroon Politechniou 9, Zografou Campus, 15780 Athens, Greece.
¹¹ Department of Organic Chemistry, Eotvos Lorand University, H-1117 Budapest, Hungary.
¹² Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eotvos Lorand University, H-1117 Budapest, Hungary.
¹³ Nencki Institute of Experimental Biology of Polish Acdemy of Sciences, Laboratory of Molecular Neurobiology, Neurobiology Center, 02-093 Warsaw, Pasteur 3 str, Poland.
¹⁴ School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, N-0316 Oslo, Norway.
¹⁵ Institut de Chimie des Milieux et Materiaux de Poitiers, UMR CNRS 7285, 86000, Poitiers, France.
¹⁶ Department of Chemistry, University of Patras, Patra, Greece.

PMID: 29366408
DOI: 10.2174/1386207321666180124093406

Abstract

Background: Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and the development of drug resistance after a first platinum-based regimen. The presence of a specific population of "cancer stem cells" could be responsible of the relapse of the tumor and the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy.

Method: We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them.

Results and conclusion: Interestingly, there were compounds active only on stem cells, only on differentiated cells, and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.

Keywords: Cancer stem cell; chemical compounds library; high-throughput screening; oncology screening; ovarian cancer; therapy resistance..

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Female
High-Throughput Screening Assays*
Humans
Molecular Structure
Neoplastic Stem Cells / drug effects*
Ovarian Neoplasms / drug therapy*
Ovarian Neoplasms / pathology
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology*
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Small Molecule Libraries