Identification of commonly regulated genes in HPV18-and HPV16-infected cervical cancer cells treated with the curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one

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.

Cytotoxic compounds from the leaves of Garcinia cowa Roxb.

The aims of this study was to isolate compounds from the leaves of methanol extract of Garcinia cowa and to evaluated their cytotoxic activity against breast (MCF-7) and lung (H-460) cell lines. The dichloromethane fraction was separated by successive silica gel column chromatography to give three compounds. Based on spectroscopic comparison with those of the literature these compounds were elucidated as methyl 2,4,6- trihydroxy-3-(3-methylbut-2-enyl)benzoate (1), garcinisidone-A (2) and methyl 4,6dihydroxy-2-(4-methoxy-5- (3-methylbut-2-enyl)-3,6-dioxocylohexa-1,4-dienyloxy)-3-(3-methylbut-2-enyl)benzoate (3). Compound 1, 2 and 3 had IC50 value of 21.0 ± 10.2 μM, 21.2 ±8.4 μM and 17.2 ± 6.2μM against MCF-7, while only compound (2) was found to be in active against H-460 with IC50 value of 18.1 ± 6.7 μM. Conclusion: The results indicate that G. cowa leaves could be important sources of natural cytotoxic compounds and only compound (2) had activity against H-460 cell lines.