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 | |
| Publication status | Published - 2018 |
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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 journal › Article
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TY - JOUR
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.
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 -