Multiple myeloma(MM)is one of the most common hematological malignancies and to date,it remains an incurable disease.In this study,we evaluated the inhibitory effect of 5-acetyloxy-6,7,8,4′-tetramethoxyflavone(5-ATMF...Multiple myeloma(MM)is one of the most common hematological malignancies and to date,it remains an incurable disease.In this study,we evaluated the inhibitory effect of 5-acetyloxy-6,7,8,4′-tetramethoxyflavone(5-ATMF),a compound from aged citrus peel extracts,on the MM U266 cell line.We found that the compound inhibited cell growth and induced cell apoptosis in multiple apoptotic assays.The apoptotic proteins caspase-3,caspase-9,and PARP(poly ADP-ribose polymerase)were cleaved when cells were treated with 5-ATMF.Along with the apoptosis process,the anti-apoptotic protein,Bcl-2(B-cell lymphoma-2),was significantly downregulated and the pro-apoptotic protein,Bax(Bcl-2 associated X protein),upregulated along with the release of cytochrome C(Cyt c)and the reduction of mitochondrial membrane potential(MMP).Notably,we found that the phosphorylation of Bad(Bcl-2/Bcl-XL-associated death promoter)was decreased but Bad remained unchanged in this process.On adding 5-ATMF to U266 cells,we observed that 5-ATMF repressed the phosphorylation of Akt(PKB Protein Kinase B PKB),thereby increasing the release of Cyt c and inhibiting the phosphorylation of Bad.These effects were enhanced by Ly294002,an inhibitor of Akt.These results suggested that 5-ATMF exerts a pro-apoptotic effect on U266 cells,possibly associated with the mitochondrial apoptotic pathway induced by the PI3K/Akt/Bad pathway.展开更多
The fruit peel of Citrus species(Chenpi),particularly those of mandarin oranges,is a useful source of food and medicine in China.Flavonoids from the citrus fruit peel are mainly polymethoxyflavones(PMFs),of which nobi...The fruit peel of Citrus species(Chenpi),particularly those of mandarin oranges,is a useful source of food and medicine in China.Flavonoids from the citrus fruit peel are mainly polymethoxyflavones(PMFs),of which nobiletin and tangeretin are the most abundant components.In the present review,we summarized the cytotoxic activities of these two PMFs to breast cancer cells.Studies have reported that these two compounds inhibit the growth of breast cancer cells by inducing apoptosis,cytostatic cell death and cell cycle arrest,or by inhibiting cell proliferation,metastasis and tumour angiogenesis,depending on the molecular subtypes of breast cancer.In vitro and in vivo cytotoxic activities involve different molecular targets and signalling pathways.Analyses on the structure-activity relationship(SAR)of nobiletin and tangeretin have shown that the presence of a methoxy group at C8 and a hydroxyl group at C3 or C5 are essential for anti-proliferative activity.Some future perspectives and research needs are suggested.Sources of information are from Pub Med,Pub Med Central,Science Direct,Google Scholar,J-Stage,Pub Chem and CNKI using keyword search.展开更多
基金This study was supported by the National Natural Science Foundation of China(Grant Nos.81172837,31240052)the Tianjin Research Program of Application Foundation and Advanced Technology(Grant No.13JCQNJC12200)and the Tianjin Innovative Research Team Grant of Agriculture Storage and Procession(TD-12-5049).
文摘Multiple myeloma(MM)is one of the most common hematological malignancies and to date,it remains an incurable disease.In this study,we evaluated the inhibitory effect of 5-acetyloxy-6,7,8,4′-tetramethoxyflavone(5-ATMF),a compound from aged citrus peel extracts,on the MM U266 cell line.We found that the compound inhibited cell growth and induced cell apoptosis in multiple apoptotic assays.The apoptotic proteins caspase-3,caspase-9,and PARP(poly ADP-ribose polymerase)were cleaved when cells were treated with 5-ATMF.Along with the apoptosis process,the anti-apoptotic protein,Bcl-2(B-cell lymphoma-2),was significantly downregulated and the pro-apoptotic protein,Bax(Bcl-2 associated X protein),upregulated along with the release of cytochrome C(Cyt c)and the reduction of mitochondrial membrane potential(MMP).Notably,we found that the phosphorylation of Bad(Bcl-2/Bcl-XL-associated death promoter)was decreased but Bad remained unchanged in this process.On adding 5-ATMF to U266 cells,we observed that 5-ATMF repressed the phosphorylation of Akt(PKB Protein Kinase B PKB),thereby increasing the release of Cyt c and inhibiting the phosphorylation of Bad.These effects were enhanced by Ly294002,an inhibitor of Akt.These results suggested that 5-ATMF exerts a pro-apoptotic effect on U266 cells,possibly associated with the mitochondrial apoptotic pathway induced by the PI3K/Akt/Bad pathway.
文摘The fruit peel of Citrus species(Chenpi),particularly those of mandarin oranges,is a useful source of food and medicine in China.Flavonoids from the citrus fruit peel are mainly polymethoxyflavones(PMFs),of which nobiletin and tangeretin are the most abundant components.In the present review,we summarized the cytotoxic activities of these two PMFs to breast cancer cells.Studies have reported that these two compounds inhibit the growth of breast cancer cells by inducing apoptosis,cytostatic cell death and cell cycle arrest,or by inhibiting cell proliferation,metastasis and tumour angiogenesis,depending on the molecular subtypes of breast cancer.In vitro and in vivo cytotoxic activities involve different molecular targets and signalling pathways.Analyses on the structure-activity relationship(SAR)of nobiletin and tangeretin have shown that the presence of a methoxy group at C8 and a hydroxyl group at C3 or C5 are essential for anti-proliferative activity.Some future perspectives and research needs are suggested.Sources of information are from Pub Med,Pub Med Central,Science Direct,Google Scholar,J-Stage,Pub Chem and CNKI using keyword search.
