Effects of garcinone E on ovarian cancer cells:endoplasmic reticulum stress,apoptosis,migration and invasion inhibition

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.