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The Antiproliferative Effects of Flavonoids and Their Mechanisms of Actions in Leukemia Cells

Author: ShiGuang
Tutor: JingYongKui
School: Shenyang Pharmaceutical University
Course: Pharmacology
Keywords: Flavonoids Leukemia Growth inhibition Apoptosis
CLC: R733.7
Type: Master's thesis
Year: 2007
Downloads: 18
Quote: 0
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Abstract


The thesis of human leukemia cell lines in vitro model , respectively, using the trypan blue exclusion method and acridine orange (AO) - ethidium bromide (EB) fluorescence double staining of 26 kinds of flavonoids cell growth inhibition and withered death induced by the inspection and application of flow cytometry ( Flow Cytometry ) , protein immunoblotting (Western Blotting) its mechanism of action was discussed . Trypan blue exclusion Experimental results show that 11 compounds demonstrated in vitro to inhibit the growth of 26 flavonoids , its IG 50 value in the 5-20μM . The QSAR analysis shows the formation of such compounds in the A ring glycosidic bond , C ring C 2 - C 3 at a hydrogenation of the double bond can be reduced to its growth inhibitory activity , and the electron withdrawing group in the B ring to enhance its growth inhibitory activity . Flow cytometry was used to further examine the growth inhibitory activity of compounds F-1 mechanism of action , the compound can block in G 2 / M phase of the cell cycle . AO-EB double fluorescent staining results showed that the growth inhibitory activity of F - 1, F -9 , and luteolin hormone were significantly induced apoptosis in HL-60 , most of which compound F-1 induction of apoptosis significantly, suggesting that the growth inhibition may partly be due to the induction of apoptosis caused . Western blot and flow cytometry results showed that the compound F-1 raised the death receptor DR5 activation of Caspase-8 and Caspase-3 Activation exogenous apoptotic pathway through the activation of Bid protein can also reduce mitochondrial membrane potential (MMP) activation of endogenous apoptosis pathway . Compound F-1 can lead to the accumulation of intracellular reactive oxygen species . Antioxidant N-acetylcysteine ??(NAC) and catalase (CAT) only partially reversed compound F-1 induction of apoptosis , suggesting that reactive oxygen species are involved at some compound F-1 's withered apoptosis -inducing action, but not play a major role . In summary , the compound F-1 is not only possible to suppress the growth of leukemia cells , and can induce apoptosis , therefore, it is expected to develop a novel anti- leukemia drug .

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia
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