Combination of a thioxodihydroquinazolinone with cisplatin eliminates ovarian cancer stem cell-like cells (CSC-LCs) and shows preclinical potential

Oncotarget
Jing MaWei Qian

Abstract

Cancer stem cell-like cells (CSC-LCs) contribute to drug resistance and recurrence of ovarian cancer. Strategies that can eradicate CSC-LCs are expected to substantially improve the outcome of ovarian cancer treatment. We have previously identified a class of thioxodihydroquinazolinone small molecules, which have strong synergistic antitumor activity with platinum drugs, the standard chemotherapeutic agents for ovarian cancer treatment. In the current study, using the activity of aldehyde dehydrogenase (ALDH) as a marker of CSC-LCs, we demonstrated that the combination of thioxodihydroquinazolinone compound 19 with cisplatin is able to diminish ALDH-high CSC-LC populations in both platinum-resistant ovarian cancer cell lines and primary ovarian cancer cells from metastatic ascites of a cisplatin-resistant patient. Compound 19 enhanced the accumulation of intracellular cisplatin in ALDH-high ovarian CSC-LCs. The combination of compound 19 with cisplatin was also able to reduce the sphere-forming capability of cisplatin-resistant ovarian cancer cells. Using a spheroid-basedin vitrometastasis model of ovarian cancer, we demonstrated that the co-administration of compound 19 with cisplatin prevents ovarian cancer spheroid cells fro...Continue Reading

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Citations

Apr 13, 2018·Journal of Translational Medicine·Iman W AchkarFatima Mraiche

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Methods Mentioned

BETA
xenografts
flow cytometry
flameless
atomic absorption spectrometry
xenograft
FACS
Assay

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