ABSTRACT
Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17), and to study the molecular pathways that contributed to the anticancer activity of MS17. Methods: PC-3 and DU145 cells were treated with 3 × EC50 (15 μM) concentration of MS17 for 24 h and were subjected to protein expression profiling using two-dimensional gel electrophoresis and protein identification by mass spectrometry. Selected differentially expressed proteins with significant P-value of P<0.05 and fold change over 1.5-folds were filtered through and ontologically classified. Mutually regulated proteins were ranked by fold change and identified as common protein targets of MS17. Results: Profiling data revealed that, the mutually down-regulated proteins included ACTB and ACTG associated with structural molecule activity, ACTN1 with cell cycle, ACTN4 with cell migration, HNRPK with apoptosis, PLST with morphogenesis and TERA with proteolysis. However, the expressions of CH60 and HS71A respectively associated with response to unfolded protein demonstrated opposing regulation in PC-3 and DU145 cells. Pathway analysis of the differentially expressed proteins in PC-3 cells demonstrated the modulation of top pathways associated with cell-cell adhesion and cytoskeletal organization while in DU145 cells the pathways were associated with proteosomal degradation, regulation of electrolytes and water, regulation control of germ cells and organization of filament assembly/disassembly. Conclusions: The findings of the present study provide an understanding on the anti-tumorigenic activity of MS17 at the proteome level and warrant further research for its potential application for the management and treatment of androgen-independent prostate cancer.
ABSTRACT
Objective:To identify commonly regulated genes in HPV-infected HeLa and CaSki cervical cancer cells treated with curcumin analogue 1,5-bis(2-hydroxyphenyl)-1A-pentadiene-3-one (MS17) and to explore potential mechanisms that underfie its eytotoxic,anti-proliferative and apoptotic activity,Methods:HeLa and CaSki cells were treated with 2 × EC5o and 3 × EC50 doses of MS 17 for 24 h and the RNA extracts were subjected to one-colour microarray-based gene expression profiling.Pair-wise significant genes (false discovery rate-corrected,P＜0.05)were analysed for fold change (FC) compared to control samples.Differentially expressed genes with FC≥2.0 (up-regulated;FC≥2.0 and down-regulated;FC≤-2.0) compared to the control samples were filtered through and analysed to create a global gene expression profile.Mutually regulated genes were ranked by FC and categorised by gene ontology.Results:Our data indicated dose-dependent regulation by MS 17 and identified top 20 mutually upand down-regulated genes each in HeLa and CaSki cells.Amongst these 17 were commonly regulated in both cell lines.These include the up-regulation of CCL26,DEFB103B,IL1RL1,LY96,GCNT3,MMPI0,MMP3,GADD45G and HSPA6,and the down-regulation of TENM2,NEBL,KIFC1,CTDSP1,IGFBP5,LTBP1,NREP and MXD3.These genes were associated with key biological functions that were proposed to mediate the anticancer activity of MS 17 in cervical cancer cells such as immune response,metabolic processes,proteolysis,programmed cell death,unfolded protein response,cell adhesion,cytoskeletal organisation,phosphatase activity,signal transduction and transcription regulator activity.Conclusions:Identification of seventeen common genes modulated by MS 17 could be used as potential therapeutic targets in both cervical cancer cell lines and the findings of this study could be used to present an insight into the potential antitumor activity of MS 17 in cervical cancer.