Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ab...Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.展开更多
Objective:To investigate the mechanism of anticancer activity of a pigment OR3 from Streptomyces coelicolor in in vitro and in vivo metastatic breast cancer models and to characterize the pigment.Methods:The anticance...Objective:To investigate the mechanism of anticancer activity of a pigment OR3 from Streptomyces coelicolor in in vitro and in vivo metastatic breast cancer models and to characterize the pigment.Methods:The anticancer mechanism was analyzed in MDA-MB-231 cells using MTT,lactate dehydrogenase,caspase,DNA fragmentation,clonogenic,flow cytometry,Western blot,and scratch assays.The effects of OR3 on xenograft mouse models were evaluated by tumor volume measurement,hematological analysis,and histopathological observation.The characterization of OR3 was also performed using gas chromatograohy-mass spectrometry and nuclear magnetic resonance spectroscopy.Results:OR3 exhibited potent cytotoxicity against MDA-MB-231 cells,with no observed effects on HEK-293 cells.Caspase-9 activation was detected in OR3-treated MDA-MB-231 cells.Flow cytometry showed a dose-dependent induction of apoptosis and cell cycle arrest at the sub-G_(1) and S phases.Furthermore,OR3 completely inhibited MDA-MB-231 cell migration and demonstrated anti-proliferative effects by downregulating the protein expression of KPNA2,XPO1,RAB5B,and p38 MAPK.In in vivo studies,OR3 was non-toxic to mice,inhibited tumor xenograft growth,and maintained normal hematological parameters and tissue architecture.Nuclear magnetic resonance spectroscopy demonstrated the presence of a prodigiosin-like compound,while gas chromatography-mass spectrometry analysis identified additional compounds in OR3.Conclusions:Our findings validate OR3 pigment as a promising compound for the treatment of metastatic breast cancer,warranting further studies.展开更多
SATB1在乳腺癌的侵袭转移中起到决定性作用,抑制SATB1的表达能够有效地控制乳腺癌的转移。该实验从茯苓中分离纯化得到均一多糖并制备硫酸化衍生物,筛选具有抑制SATB1表达的多糖成分。茯苓经醇提去除小分子成分,水提醇沉后得茯苓粗多糖P...SATB1在乳腺癌的侵袭转移中起到决定性作用,抑制SATB1的表达能够有效地控制乳腺癌的转移。该实验从茯苓中分离纯化得到均一多糖并制备硫酸化衍生物,筛选具有抑制SATB1表达的多糖成分。茯苓经醇提去除小分子成分,水提醇沉后得茯苓粗多糖PPS,PPS经DEAE Sepharose Fast Flow阴离子交换树脂分离和Superdex-75系列凝胶纯化后得PPSW-1,并对PPSW-1进行结构分析、硫酸衍生化和抑制人乳腺癌MDA-MB-231细胞迁移作用考察。结果显示从茯苓中得到一种具有抑制人乳腺癌MDA-MB-231细胞迁移作用的均一多糖PPSW-1,相对分子质量为3. 06×104,结构为1,3连接α-D-半乳聚糖为主链,1,6连接α-D-半乳聚糖为支链的多糖,PPSW-1表现出较强的抑制细胞迁移的作用,经硫酸衍生化后产物Sul-W-1活性较PPSW-1并未有明显的增强,但水溶性有明显增加,并且发现茯苓多糖及其硫酸化衍生物能抑制SATB1的表达。该研究从茯苓中成功分离到具有抑制人乳腺癌MDA-MB-231细胞迁移作用的均一多糖,并经过硫酸衍生化得到活性不变溶解性更好的多糖,该发现为茯苓多糖及其衍生物的抗乳腺癌研究提供依据。展开更多
文摘Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.
文摘Objective:To investigate the mechanism of anticancer activity of a pigment OR3 from Streptomyces coelicolor in in vitro and in vivo metastatic breast cancer models and to characterize the pigment.Methods:The anticancer mechanism was analyzed in MDA-MB-231 cells using MTT,lactate dehydrogenase,caspase,DNA fragmentation,clonogenic,flow cytometry,Western blot,and scratch assays.The effects of OR3 on xenograft mouse models were evaluated by tumor volume measurement,hematological analysis,and histopathological observation.The characterization of OR3 was also performed using gas chromatograohy-mass spectrometry and nuclear magnetic resonance spectroscopy.Results:OR3 exhibited potent cytotoxicity against MDA-MB-231 cells,with no observed effects on HEK-293 cells.Caspase-9 activation was detected in OR3-treated MDA-MB-231 cells.Flow cytometry showed a dose-dependent induction of apoptosis and cell cycle arrest at the sub-G_(1) and S phases.Furthermore,OR3 completely inhibited MDA-MB-231 cell migration and demonstrated anti-proliferative effects by downregulating the protein expression of KPNA2,XPO1,RAB5B,and p38 MAPK.In in vivo studies,OR3 was non-toxic to mice,inhibited tumor xenograft growth,and maintained normal hematological parameters and tissue architecture.Nuclear magnetic resonance spectroscopy demonstrated the presence of a prodigiosin-like compound,while gas chromatography-mass spectrometry analysis identified additional compounds in OR3.Conclusions:Our findings validate OR3 pigment as a promising compound for the treatment of metastatic breast cancer,warranting further studies.
文摘SATB1在乳腺癌的侵袭转移中起到决定性作用,抑制SATB1的表达能够有效地控制乳腺癌的转移。该实验从茯苓中分离纯化得到均一多糖并制备硫酸化衍生物,筛选具有抑制SATB1表达的多糖成分。茯苓经醇提去除小分子成分,水提醇沉后得茯苓粗多糖PPS,PPS经DEAE Sepharose Fast Flow阴离子交换树脂分离和Superdex-75系列凝胶纯化后得PPSW-1,并对PPSW-1进行结构分析、硫酸衍生化和抑制人乳腺癌MDA-MB-231细胞迁移作用考察。结果显示从茯苓中得到一种具有抑制人乳腺癌MDA-MB-231细胞迁移作用的均一多糖PPSW-1,相对分子质量为3. 06×104,结构为1,3连接α-D-半乳聚糖为主链,1,6连接α-D-半乳聚糖为支链的多糖,PPSW-1表现出较强的抑制细胞迁移的作用,经硫酸衍生化后产物Sul-W-1活性较PPSW-1并未有明显的增强,但水溶性有明显增加,并且发现茯苓多糖及其硫酸化衍生物能抑制SATB1的表达。该研究从茯苓中成功分离到具有抑制人乳腺癌MDA-MB-231细胞迁移作用的均一多糖,并经过硫酸衍生化得到活性不变溶解性更好的多糖,该发现为茯苓多糖及其衍生物的抗乳腺癌研究提供依据。
