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 MajerF Hudecz, S Bosze, B Kaminska, T V Hansen, P Bertrand, C M Athanassopoulos, G Damia

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)50-56
Number of pages7
JournalCombinatorial Chemistry and High Throughput Screening
Volume21
Issue number1
DOIs
Publication statusPublished - 2018

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Small Molecule Libraries
Chemical compounds
Neoplastic Stem Cells
Stem cells
Ovarian Neoplasms
Screening
Throughput
Tumors
Stem Cells
Cells
High-Throughput Screening Assays
Delayed Diagnosis
Platinum
Drug Resistance
Pharmaceutical Preparations
Population
Assays
Neoplasms
Recurrence
Therapeutics

Keywords

  • Antineoplastic Agents/chemistry
  • 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
  • Small Molecule Libraries/chemistry
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Cite this

A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells. / Ricci, F; Carrassa, L; Christodoulou, M S; Passarella, D; Michel, B; Benhida, R; Martinet, N; Hunyadi, A; Ioannou, E; Roussis, V; Musso, L; Dallavalle, S; Silvestri, R; Westwood, N; Mori, M; Ingallina, C; Botta, B; Kavetsou, E; Detsi, A; Majer, Z; Hudecz, F; Bosze, S; Kaminska, B; Hansen, T V; Bertrand, P; Athanassopoulos, C M; Damia, G.

In: Combinatorial Chemistry and High Throughput Screening, Vol. 21, No. 1, 2018, p. 50-56.

Research output: Contribution to journalArticle

Ricci, F, Carrassa, L, Christodoulou, MS, Passarella, D, Michel, B, Benhida, R, Martinet, N, Hunyadi, A, Ioannou, E, Roussis, V, Musso, L, Dallavalle, S, Silvestri, R, Westwood, N, Mori, M, Ingallina, C, Botta, B, Kavetsou, E, Detsi, A, Majer, Z, Hudecz, F, Bosze, S, Kaminska, B, Hansen, TV, Bertrand, P, Athanassopoulos, CM & Damia, G 2018, 'A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells', Combinatorial Chemistry and High Throughput Screening, vol. 21, no. 1, pp. 50-56. https://doi.org/10.2174/1386207321666180124093406
Ricci, F ; Carrassa, L ; Christodoulou, M S ; Passarella, D ; Michel, B ; Benhida, R ; Martinet, N ; Hunyadi, A ; Ioannou, E ; Roussis, V ; Musso, L ; Dallavalle, S ; Silvestri, R ; Westwood, N ; Mori, M ; Ingallina, C ; Botta, B ; Kavetsou, E ; Detsi, A ; Majer, Z ; Hudecz, F ; Bosze, S ; Kaminska, B ; Hansen, T V ; Bertrand, P ; Athanassopoulos, C M ; Damia, G. / A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells. In: Combinatorial Chemistry and High Throughput Screening. 2018 ; Vol. 21, No. 1. pp. 50-56.
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T1 - A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells

AU - Ricci, F

AU - Carrassa, L

AU - Christodoulou, M S

AU - Passarella, D

AU - Michel, B

AU - Benhida, R

AU - Martinet, N

AU - Hunyadi, A

AU - Ioannou, E

AU - Roussis, V

AU - Musso, L

AU - Dallavalle, S

AU - Silvestri, R

AU - Westwood, N

AU - Mori, M

AU - Ingallina, C

AU - Botta, B

AU - Kavetsou, E

AU - Detsi, A

AU - Majer, Z

AU - Hudecz, F

AU - Bosze, S

AU - Kaminska, B

AU - Hansen, T V

AU - Bertrand, P

AU - Athanassopoulos, C M

AU - Damia, G

N1 - Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

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KW - Dose-Response Relationship, Drug

KW - Drug Screening Assays, Antitumor

KW - Female

KW - High-Throughput Screening Assays

KW - Humans

KW - Molecular Structure

KW - Neoplastic Stem Cells/drug effects

KW - Ovarian Neoplasms/drug therapy

KW - Small Molecule Libraries/chemistry

KW - Structure-Activity Relationship

KW - Tumor Cells, Cultured

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JO - Combinatorial Chemistry and High Throughput Screening

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SN - 1386-2073

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ER -