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
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.
