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https://hdl.handle.net/10216/120340
Author(s): | Freitas S. Martins R. Campos A. Azevedo J. Osório H. Costa M. Barros P. Vasconcelos V. Urbatzka R. |
Title: | Insights into the potential of picoplanktonic marine cyanobacteria strains for cancer therapies - Cytotoxic mechanisms against the RKO colon cancer cell line |
Publisher: | Elsevier |
Issue Date: | 2016 |
Abstract: | Purpose In this work, we analysed the potential of picoplanktonic marine cyanobacteria strains as a source of anticancer compounds by elucidating the cytotoxic mechanisms of an ethyl acetate fraction of Cyanobium sp. (LEGE06113) and the Synechocystis salina (LEGE06155) on the RKO colon adenocarcinoma cell line. Methods Cytotoxicity was analysed by MTT. Effects on cells were evaluated by mRNA expression of cell cycle and apoptotic genes, flow cytometry (cell cycle), qualitative and quantitative fluorescence microscopy (apoptosis), and quantitative proteomics. Results IC50 values were 27.01 and 8.03 μg/ml for Cyanobium sp., and 37.71 and 17.17 μg/ml for Synechocystis salina, after 24 h and 48 h, respectively. Exposure to the Cyanobium sp. fraction increased 2.5 fold BCL-2 mRNA expression (p < 0.05), and altered proteins (13, p < 0.05) belonged to apoptosis (PSMA5, PSMA7, TPT1, UBE2K), cell cycle (EIF4E, PCNA), cellular metabolism (AHSG, GLO1, ATP5H, HSP90AB1, NME1, HNRNPC) and cell structure (KRT10). Exposure to the Synechocystis salina fraction decreased 2fold CCNB1 mRNA expression (p < 0.05). Accordingly, flow cytometry demonstrated a decrease of cells in the G0/G1 and S phase (p < 0.05), indicating a cell cycle arrest at the G2/M transition. Fluorescence microscopy confirmed a higher level of apoptosis compared to the solvent control group (p < 0.01). Altered proteins (6, p < 0.05) belonged to apoptosis (HSPD1, UBE2K), protein metabolism (PKM, PDIA3) and cell structure (KRT10, KRT1). Conclusion Since induction of cytotoxicity is a very broad parameter, the study demonstrates the potential of picocyanobacteria to produce bioactive compounds that target cancer cells via different molecular mechanisms. © 2016 Elsevier. |
Subject: | acetic acid ethyl ester algal extract Cyanobium extract cytotoxic agent messenger RNA protein bcl 2 Synechocystis salina extract unclassified drug AHSG gene apoptosis Article ATP5H gene bacterial strain BCL 2 gene cancer cell line cancer therapy CCNB1 gene cell cycle cell cycle arrest cell cycle G0 phase cell cycle G1 phase cell cycle M phase cell cycle S phase cell metabolism cell structure colon adenocarcinoma colon adenocarcinoma cell line controlled study cyanobacterium Cyanobium cytotoxicity test drug cytotoxicity EIF4E gene epifluorescence microscopy flow cytometry fluorescence microscopy G2 phase cell cycle checkpoint gene gene expression GLO1 gene HNRNPC gene HSP90AB1 gene HSPD1 gene human human cell IC50 KRT1 gene KRT10 gene NME1 gene nonhuman PCNA gene priority journal protein metabolism proteomics PSMA5 gene PSMA7 gene qualitative analysis quantitative analysis Synechocystis salina TPT1 gene UBE2K gene |
URI: | https://hdl.handle.net/10216/120340 |
Source: | Toxicon, vol. 119, p. 140-151 |
Related Information: | info:eu-repo/grantAgreement/FCT/5876/147268/PT |
Document Type: | Artigo em Revista Científica Internacional |
Rights: | restrictedAccess |
Appears in Collections: | CIIMAR - Artigo em Revista Científica Internacional |
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