Insights into the potential of picoplanktonic marine cyanobacteria strains for cancer therapies – Cytotoxic mechanisms against the RKO colon cancer cell line

Freitas, Sara; Martíns, Rosário; Campos, Alexandre; Azevedo, Joana; Osório, Hugo; Costa, Margarida; Barros, P.; Vasconcelos, Vı́tor; Urbatzka, Ralph

doi:10.1016/j.toxicon.2016.05.016

Cited by 16 publications

(15 citation statements)

References 39 publications

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“…The most famous example is brentuximab vedotin, which targets CD30 and microtubules, and is used for the treatment of malignant lymphoma after approval by the Federal Drug Agency [ 17 ]. Currently, 16 compounds derived from cyanobacteria are in different phases of clinical trials for the treatment of cancer [ 18 ]. Already-characterized modes of actions of bioactive compounds from cyanobacteria are very diverse and include classical anticancer targets, as microtubulin and actin, or non-classical targets, as histone deacetylases and proteasome [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Hierridin B Isolated from a Marine Cyanobacterium Alters VDAC1, Mitochondrial Activity, and Cell Cycle Genes on HT-29 Colon Adenocarcinoma Cells

et al. 2016

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Background: Hierridin B was isolated from a marine cyanobacterium Cyanobium sp. strain and induced cytotoxicity selectively in HT-29 adenocarcinoma cells. The underlying molecular mechanism was not yet elucidated. Methods: HT-29 cells were exposed to the IC50 concentration of hierridin B (100.2 μM) for 48 h. Non-targeted proteomics was performed using 2D gel electrophoresis and MALDI-TOF/TOF mass spectrometry. The mRNA expression of apoptotic and cell cycle genes were analyzed by real-time PCR. Automated quantification of 160 cytoplasm and mitochondrial parameter was done by fluorescence microscopy using CellProfiler software. Results: Proteomics identified 21 significant different proteins, which belonged to protein folding/synthesis and cell structure amongst others. Increase of VDAC1 protein responsible for formation of mitochondrial channels was confirmed by mRNA expression. A 10-fold decrease of cytoskeleton proteins (STMN1, TBCA) provided a link to alterations of the cell cycle. CCNB1 and CCNE mRNA were decreased two-fold, and P21CIP increased 10-fold, indicative of cell cycle arrest. Morphological analysis of mitochondrial parameter confirmed a reduced mitochondrial activity. Conclusion: Hierridin B is a potential anticancer compound that targets mitochondrial activity and function.

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Section: Discussionmentioning

confidence: 99%

Hierridin B Isolated from a Marine Cyanobacterium Alters VDAC1, Mitochondrial Activity, and Cell Cycle Genes on HT-29 Colon Adenocarcinoma Cells

et al. 2016

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“…The MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was used to assess the cytotoxicity of different concentrations of portoamides on the studied cell lines as described in [ 5 ]. Cells were seeded in 96-well plates at 1 x 10 4 cells/cm 2 and the final exposure concentrations of portoamides ranged from 78 ng/mL to 10μ/mL.…”

Section: Methodsmentioning

confidence: 99%

“…The Isoelectric focusing (IEF) of each sample was done based on [ 5 ] using immobilized pH gradient (IPG) strips (pH 3–10, 17cm) (BioRad). For SDS-PAGE electrophoresis, 12.5% polyacrylamide gels were used in cooled vertical electrophoresis unit (Hoefer, SE900, Massachusetts, USA) connected to a power supply (Hoefer, PS600).…”

Section: Methodsmentioning

confidence: 99%

“…After staining, each gel was washed with distilled water, and stored in 200 mL of ammonium sulfate (20% p/v). Images of the gels were acquired using Quantity One (BioRad) and the densitometer GS-800 (Bio-Rad), image analysis with the PDQuest 2D analysis software (BioRad) as described in [ 5 ].…”

Section: Methodsmentioning

confidence: 99%

“…Brentuximab vedotin targets CD30 and microtubules, and is used for the treatment of anaplastic large T-cell systemic malignant lymphoma and Hodgkin’s disease [ 4 ]. Our own group demonstrated that picocyanobacteria have the capacity to induce cytotoxicity in human cancer cells via different modes of actions [ 5 ] and that hierridin B, a metabolite from the marine cyanobacterium Cyanobium sp . decreased mitochondrial activity and function [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxicity of portoamides in human cancer cells and analysis of the molecular mechanisms of action

Ribeiro¹,

Lemos²,

Preto³

et al. 2017

PLoS ONE

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Portoamides are cyclic peptides produced and released by the cyanobacterial strain Phormidium sp. presumably to interfere with other organisms in their ecosystems ("allelopathy"). Portoamides were previously demonstrated to have an antiproliferative effect on human lung carcinoma cells, but the underlying mechanism of this activity has not been described. In the present work, the effects of portoamides on proliferation were examined in eight human cancer cell lines and two non-carcinogenic cell lines, and major differences in sensitivities were observed. To generate hypotheses with regard to molecular mechanisms of action, quantitative proteomics using 2D gel electrophoresis and MALDI-TOF/TOF were performed on the colon carcinoma cell line HT-29. The expression of proteins involved in energy metabolism (mitochondrial respiratory chain and pentose phosphate pathway) was found to be affected. The hypothesis of altered energy metabolism was tested in further experiments. Exposure to portoamides resulted in reduced cellular ATP content, likely due to decreased mitochondrial energy production. Mitochondrial hyperpolarization and reduced mitochondrial reductive capacity was observed in treated cells. Furthermore, alterations in the expression of peroxiredoxins (PRDX4, PRDX6) and components of proteasome subunits (PSB4, PSA6) were observed in portoamide-treated cells, but these alterations were not associated with detectable increases in oxidative stress. We conclude that the cytotoxic activity of portoamides is associated with disturbance of energy metabolism, and alterations in mitochondrial structure and function.

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Potential use of nuisance cyanobacteria as a source of anticancer agents

Lee

Depuydt

Choi

et al. 2021

Natural Bioactive Compounds

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Insights into the potential of picoplanktonic marine cyanobacteria strains for cancer therapies – Cytotoxic mechanisms against the RKO colon cancer cell line

Cited by 16 publications

References 39 publications

Hierridin B Isolated from a Marine Cyanobacterium Alters VDAC1, Mitochondrial Activity, and Cell Cycle Genes on HT-29 Colon Adenocarcinoma Cells

Hierridin B Isolated from a Marine Cyanobacterium Alters VDAC1, Mitochondrial Activity, and Cell Cycle Genes on HT-29 Colon Adenocarcinoma Cells

Cytotoxicity of portoamides in human cancer cells and analysis of the molecular mechanisms of action

Potential use of nuisance cyanobacteria as a source of anticancer agents

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