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1.
Tumour Biol ; 39(5): 1010428317691689, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28466786

RESUMO

Current standard chemotherapy for late stage ovarian cancer is found unsuccessful due to relapse after completing the regimens. After completing platinum-based chemotherapy, 70% of patients develop relapse and resistance. Recent evidence proves ovarian cancer stem cells as the source of resistance. Therefore, treatment strategy to target both cancer stem cells and normal stem cells is essential. In this study, we developed a novel chalcone derivative as novel drug candidate for ovarian cancer treatment. We found that methoxyphenyl chalcone was effective to eliminate ovarian cancer cells when given either as monotherapy or in combination with cisplatin. We found that cell viability of ovarian cancer cells was decreased through apoptosis induction. Dephosphorylation of Bcl2-associated agonist of cell death protein was increased after methoxyphenyl chalcone treatment that led to activation of caspases. Interestingly, this drug also worked as a G2/M checkpoint modulator with alternative ways of DNA damage signal-evoking potential that might work to increase response after cisplatin treatment. In addition, methoxyphenyl chalcone was able to suppress autophagic flux and stemness regulator in ovarian spheroids that decreased their survival. Therefore, combination of methoxyphenyl chalcone and cisplatin showed synergistic effects. Taken together, we believe that our novel compound is a promising novel therapeutic agent for effective clinical treatment of ovarian cancer.


Assuntos
Chalcona/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/dietoterapia , Neoplasias Ovarianas/dietoterapia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Dano ao DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Neoplasias Epiteliais e Glandulares/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/patologia , Fosforilação/efeitos dos fármacos
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