Gastric cancer(GC)is a common malignancy across the world,ranking third among all cancer-related deaths globally.At present,natural products are the vital sources of antitumor drug development.As the natural flavonoid...Gastric cancer(GC)is a common malignancy across the world,ranking third among all cancer-related deaths globally.At present,natural products are the vital sources of antitumor drug development.As the natural flavonoid,(R)-7,3′-dihydroxy-4′-methoxy-8-methylflavane(DHMMF)was separated in Resina Draconis previously.In addition,it is also a natural sweet taste modulator.However,its anti-GC activity and associated mechanisms are still unclear.In this study,DHMMF exhibited a suppressive impact on HGC-27 and MGC-803 cell proliferation,while simultaneously enhancing their apoptosis.Based on RNA sequencing and immunoblotting,mitogen-activated protein kinase(MAPK)/c-Jun pathway activation was partly associated with DHMMF’s anti-GC activity.By immunoblotting,acridine orange staining,immunofluorescence analysis,transmission electron microscopy,and immunohistochemical staining,it was demonstrated that DHMMF significantly activated autophagy in GC.Inhibiting autophagy obviously reduced DHMMF sensitivity in human GC cells.DHMMF treatment triggered autophagy by up-regulating Atg3/LC3 axis in human GC cells.Notably,this treatment significantly impeded the growth of two xenograft tumor models established from HGC-27 or MGC-803 GC cells.DHMMF treatment effectively hindered GC cell proliferation,promoted their apoptosis,and activated autophagy of cancer tissues within nude mice models.Therefore,DHMMF suppressed human GC cell growth by inducing apoptosis and autophagic cell death through activating MAPK/c-Jun signaling pathway and up-regulation of Atg3/LC3 signaling axis.DHMMF is the candidate drug for treating GC.展开更多
基金financially supported by the National Natural Science Foundation of China(82074072,81873044)the Beijing Natural Science Foundation(J230034)+2 种基金the Fundamental Research Funds for the Central Universities(2023-JYB-JBQN-051)the Talent Cultivation Project of Beijing University of Chinese Medicine(JZPY202206)The Youth Qihuang Scholar Support Project of National Administration of Traditional Chinese Medicine.
文摘Gastric cancer(GC)is a common malignancy across the world,ranking third among all cancer-related deaths globally.At present,natural products are the vital sources of antitumor drug development.As the natural flavonoid,(R)-7,3′-dihydroxy-4′-methoxy-8-methylflavane(DHMMF)was separated in Resina Draconis previously.In addition,it is also a natural sweet taste modulator.However,its anti-GC activity and associated mechanisms are still unclear.In this study,DHMMF exhibited a suppressive impact on HGC-27 and MGC-803 cell proliferation,while simultaneously enhancing their apoptosis.Based on RNA sequencing and immunoblotting,mitogen-activated protein kinase(MAPK)/c-Jun pathway activation was partly associated with DHMMF’s anti-GC activity.By immunoblotting,acridine orange staining,immunofluorescence analysis,transmission electron microscopy,and immunohistochemical staining,it was demonstrated that DHMMF significantly activated autophagy in GC.Inhibiting autophagy obviously reduced DHMMF sensitivity in human GC cells.DHMMF treatment triggered autophagy by up-regulating Atg3/LC3 axis in human GC cells.Notably,this treatment significantly impeded the growth of two xenograft tumor models established from HGC-27 or MGC-803 GC cells.DHMMF treatment effectively hindered GC cell proliferation,promoted their apoptosis,and activated autophagy of cancer tissues within nude mice models.Therefore,DHMMF suppressed human GC cell growth by inducing apoptosis and autophagic cell death through activating MAPK/c-Jun signaling pathway and up-regulation of Atg3/LC3 signaling axis.DHMMF is the candidate drug for treating GC.
