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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
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
cytotoxicity test
drug cytotoxicity
EIF4E gene
epifluorescence microscopy
flow cytometry
fluorescence microscopy
G2 phase cell cycle checkpoint
gene expression
GLO1 gene
HSP90AB1 gene
HSPD1 gene
human cell
KRT1 gene
KRT10 gene
NME1 gene
PCNA gene
priority journal
protein metabolism
PSMA5 gene
PSMA7 gene
qualitative analysis
quantitative analysis
Synechocystis salina
TPT1 gene
UBE2K gene
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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