OBJECTIVE Garcinone E,a xanthone derivative isolated from mangosteen,has been reported to have cytotoxic capacities.We aim to study the anticancer effects of garcinone E on ovarian cancer cells.METHODS MTT assay,LDH r...OBJECTIVE Garcinone E,a xanthone derivative isolated from mangosteen,has been reported to have cytotoxic capacities.We aim to study the anticancer effects of garcinone E on ovarian cancer cells.METHODS MTT assay,LDH release assay,Hoechst33342 staining,AnnexinⅤ/PI staining,and JC-1 staining were used to test the antitumor abilities on several ovarian cancer cell lines,and wound-healing assay,transwell assay,and gelatin zymography were carried out to examine the migratory and invasive effects of malignant ovarian cancer HEY cells.Relevant m RNA transcription and protein expression were evaluated by Western blotting.RESULTS Garcinone E treatment significantly inhibited the proliferation and caused cell death on ovarian cancer HEY,A2780 as well as A2780-palicitaxel resistant cells.It induced endoplasmic reticulum stress in HEY cells and activated IRE signaling pathway,which provided protection on HEY cells.Meanwhile,knocking down of IRE-1αby si RNA further activated caspase cascade and caused more cell death.On the other hand,garcinone E eliminated migrative ability of HEY cells by reducing the expression of Rho A and Rac,and it blockaded invasion by down-regulating the protein level of MMP-9 and-2,and up-regulating the protein level of TIMP-1 and-2.Garcinone E-reduced activities of MMP-9 and-2 were confirmed by gelatin zymography assay.CONCLUSION Our finding demonstrated that garcinone E exerts anticancer activities by inducing apoptosis,and suppressing migration and invasion on ovarian cancer cells,which demonstrated certain therapeutic potential of garcinone E on ovarian cancer.展开更多
Background:High proliferative rate of cancer cells requires autophagy to maintain nutrient supply and intracellular homeostasis.As a result,impairing autophagic flux could be a novel strategy of cancer therapy.Aims an...Background:High proliferative rate of cancer cells requires autophagy to maintain nutrient supply and intracellular homeostasis.As a result,impairing autophagic flux could be a novel strategy of cancer therapy.Aims and Objectives:In this study,the mechanism of a xanthone derivative isolated from Garcinia mangostana,garcinone E(GE),was investigated.Materials and Methods:Fluorescence assay was used to observe the accumulation and location of autophagosome and lysosome.Flow cytometry with Lyso-tracker red,MDC,and AO staining were applied to evaluate the lysosome accumulation and cellular acidity.Western blot and RT-qPCR were performed to evaluate the protein and mRNA levels,respectively.Results:GE could cause enhancement of LC3 II and p62 and the accumulation of autophagosome and lysosome.Meanwhile,it limited the protein level of Rab7,increased lysosomal pH,and inhibited the maturation of lysosomal hydrolases such as Cathepsin L,therefore blockaded the fusion of autophagosome and lysosome.Moreover,GE acted as a TFEB modulator by downregulating its protein level,which might contribute to autophagy dysfunction in ovarian cancer cells.Conclusions:GE interfered autophagosome–lysosome fusion in cancer cells,which demonstrated its application as an autophagy regulator and a potential therapeutic agent.展开更多
基金The project supported by Science and Technology Development Fund,Macao S.A.R(FDCT)(074/2012/A3)Research Fund of University of Macao(MYRG2015-00091-ICMS-QRCM,MYRG2015-00101-ICMS-QRCM and CPG2014-00012-ICMS)
文摘OBJECTIVE Garcinone E,a xanthone derivative isolated from mangosteen,has been reported to have cytotoxic capacities.We aim to study the anticancer effects of garcinone E on ovarian cancer cells.METHODS MTT assay,LDH release assay,Hoechst33342 staining,AnnexinⅤ/PI staining,and JC-1 staining were used to test the antitumor abilities on several ovarian cancer cell lines,and wound-healing assay,transwell assay,and gelatin zymography were carried out to examine the migratory and invasive effects of malignant ovarian cancer HEY cells.Relevant m RNA transcription and protein expression were evaluated by Western blotting.RESULTS Garcinone E treatment significantly inhibited the proliferation and caused cell death on ovarian cancer HEY,A2780 as well as A2780-palicitaxel resistant cells.It induced endoplasmic reticulum stress in HEY cells and activated IRE signaling pathway,which provided protection on HEY cells.Meanwhile,knocking down of IRE-1αby si RNA further activated caspase cascade and caused more cell death.On the other hand,garcinone E eliminated migrative ability of HEY cells by reducing the expression of Rho A and Rac,and it blockaded invasion by down-regulating the protein level of MMP-9 and-2,and up-regulating the protein level of TIMP-1 and-2.Garcinone E-reduced activities of MMP-9 and-2 were confirmed by gelatin zymography assay.CONCLUSION Our finding demonstrated that garcinone E exerts anticancer activities by inducing apoptosis,and suppressing migration and invasion on ovarian cancer cells,which demonstrated certain therapeutic potential of garcinone E on ovarian cancer.
基金supported by the Science and Technology Development Fund,Macao SAR(File no.176/2017/A3)
文摘Background:High proliferative rate of cancer cells requires autophagy to maintain nutrient supply and intracellular homeostasis.As a result,impairing autophagic flux could be a novel strategy of cancer therapy.Aims and Objectives:In this study,the mechanism of a xanthone derivative isolated from Garcinia mangostana,garcinone E(GE),was investigated.Materials and Methods:Fluorescence assay was used to observe the accumulation and location of autophagosome and lysosome.Flow cytometry with Lyso-tracker red,MDC,and AO staining were applied to evaluate the lysosome accumulation and cellular acidity.Western blot and RT-qPCR were performed to evaluate the protein and mRNA levels,respectively.Results:GE could cause enhancement of LC3 II and p62 and the accumulation of autophagosome and lysosome.Meanwhile,it limited the protein level of Rab7,increased lysosomal pH,and inhibited the maturation of lysosomal hydrolases such as Cathepsin L,therefore blockaded the fusion of autophagosome and lysosome.Moreover,GE acted as a TFEB modulator by downregulating its protein level,which might contribute to autophagy dysfunction in ovarian cancer cells.Conclusions:GE interfered autophagosome–lysosome fusion in cancer cells,which demonstrated its application as an autophagy regulator and a potential therapeutic agent.
