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Antitumor Effect Of Pomolic Acid In Acute Myeloid Leukemia Cells Involves Cell Death, Decreased Cell Growth And Topoisomerases Inhibition.
Anti-cancer Agents in Medicinal Chemistry 2018 April 13
BACKGROUND: Acute myeloid leukemia (AML) represent the largest number of annual deaths from hematologic malignancy. In the United-States, it is estimated that 21.380 individuals will be diagnosed with AML and 49.5% of patients will die in 2017. Therefore, the searching for novel compounds capable of increasing the overall survival rate to the treatment of AML cells is urgent.
OBJECTIVES: To investigate the cytotoxicity effect of the natural compound PA and to explore the mechanism of action of PA in AML cell lines with different phenotypes.
METHODS: It was used three different AML cell lines, HL60, U937 and Kasumi-1 cells with different mechanisms of resistance to analyze the effect of PA on the cell cycle progression, on DNA intercalation and on human DNA topoisomerases (hTopo I and IIα) in vitro studies. Theoretical experiments of the inhibition of hTopo I and IIα were done to explore the binding modes of PA.
RESULTS: PA reduced cell viability, induced cell death, increased sub-G0/G1 accumulation and activated caspases pathway in all cell lines, altered the cell cycle distribution and inhibited the catalytic activity of both human DNA topoisomerases.
CONCLUSION: Finally, this study showed that PA has powerful antitumor activity against AML cells suggesting that this natural compound might be a potent antineoplastic agent to improve the treatment scheme of this neoplasm.
OBJECTIVES: To investigate the cytotoxicity effect of the natural compound PA and to explore the mechanism of action of PA in AML cell lines with different phenotypes.
METHODS: It was used three different AML cell lines, HL60, U937 and Kasumi-1 cells with different mechanisms of resistance to analyze the effect of PA on the cell cycle progression, on DNA intercalation and on human DNA topoisomerases (hTopo I and IIα) in vitro studies. Theoretical experiments of the inhibition of hTopo I and IIα were done to explore the binding modes of PA.
RESULTS: PA reduced cell viability, induced cell death, increased sub-G0/G1 accumulation and activated caspases pathway in all cell lines, altered the cell cycle distribution and inhibited the catalytic activity of both human DNA topoisomerases.
CONCLUSION: Finally, this study showed that PA has powerful antitumor activity against AML cells suggesting that this natural compound might be a potent antineoplastic agent to improve the treatment scheme of this neoplasm.
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