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

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 journal › Article › peer-review

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 language	English
Pages (from-to)	50-56
Number of pages	7
Journal	Combinatorial Chemistry and High Throughput Screening
Volume	21
Issue number	1
DOIs	https://doi.org/10.2174/1386207321666180124093406
Publication status	Published - 2018

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

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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., ... Damia, G. (2018). A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells. Combinatorial Chemistry and High Throughput Screening, 21(1), 50-56. https://doi.org/10.2174/1386207321666180124093406

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

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title = "A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells",

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 = "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",

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

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year = "2018",

doi = "10.2174/1386207321666180124093406",

language = "English",

volume = "21",

pages = "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

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.

KW - Antineoplastic Agents/chemistry

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

U2 - 10.2174/1386207321666180124093406

DO - 10.2174/1386207321666180124093406

M3 - Article

C2 - 29366408

VL - 21

SP - 50

EP - 56

JO - Combinatorial Chemistry and High Throughput Screening

JF - Combinatorial Chemistry and High Throughput Screening

SN - 1386-2073

IS - 1

ER -

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

Abstract

Keywords

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