title: Differential proteomic analysis of HL60 cells treated with secalonic             acid F reveals caspase 3-induced cleavage of Rho GDP dissociation inhibitor 2.
abstract: Secalonic acid F (SAF) has been previously identified, however, little is             known about its cytotoxic activity and related cytotoxic mechanism. The aim of             this study was to evaluate the cytotoxic activity of SAF isolated from a deep             sea originated fungus Penicillium sp. F11 in HL60 cells and to analyze the differences             in protein expression of HL60 cells treated with SAF. The CCK-8 assay and Annexin V-FLUOS/PI             assay indicated that SAF displayed dose- and time-dependent inhibition of HL60             cell proliferation and induced apoptosis. Two-dimensional gel electrophoresis             (2-DE) analysis of HL60 cells treated with SAF (4 µg/ml) revealed 10 differentially             expressed protein spots (P<0.05), 5 upregulated and 5 downregulated. Three             spots (1 downregulated and 2 upregulated) were identified as Rho GDP dissociation             inhibitor 2 (RhoGDI 2) proteins by MALDI-TOF MS. Western blotting further demonstrated             the decreased abundance of full-length RhoGDI 2 together with the increased abundance             of caspase 3-cleaved product of RhoGDI 2. The caspase 3 inhibitor Ac-DEVD-CHO             could suppress the cytotoxic effect of SAF and significantly block the cleavage             of RhoGDI 2. RhoGDI 2 is a cytosolic regulator of Rho GTPase and the caspase 3-cleaved             product of RhoGDI 2 can advance progression of the apoptotic process. Our data             showed that SAF may modulate RhoGDI 2 levels in HL60 cells, thereby potentially             disrupting cell signaling pathways important for HL60 cell function.
authors.affiliation: Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration, Xiamen 361005, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Yi
authors.forename: Yuqiao
authors.initials: Y
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Tianhua
authors.initials: T
authors.lastname: Zhong
authors.forename: Yinkun
authors.initials: Y
authors.lastname: Qiu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wu
authors.forename: Xixiang
authors.initials: X
authors.lastname: Tang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020543:Proteome; D044004:Xanthones / Q000494:pharmacology*; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D020543:Proteome; D044004:Xanthones; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; C009218:secalonic acid; D053148:Caspase 3