Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Biology (Basel)
2019 Oct 09;84:. doi: 10.3390/biology8040076.
Show Gene links
Show Anatomy links
Cytotoxic Potential of the Coelomic Fluid Extracted from the Sea Cucumber Holothuria tubulosa against Triple-Negative MDA-MB231 Breast Cancer Cells.
Luparello C
,
Ragona D
,
Asaro DML
,
Lazzara V
,
Affranchi F
,
Celi M
,
Arizza V
,
Vazzana M
.
Abstract
Growing evidence has demonstrated that the extracts of different holothurian species exert beneficial effects on human health. Triple negative breast cancers (TNBC) are highly malignant tumors that present a poor prognosis due to the lack of effective targeted therapies. In the attempt to identify novel compounds that might counteract TNBC cell growth, we studied the effect of the exposure of the TNBC cell line MDA-MB231 to total and filtered aqueous extracts of the coelomic fluid obtained from the sea cucumber Holoturia tubulosa, a widespread species in the Mediterranean Sea. In particular, we examined cell viability and proliferative behaviour, cell cycle distribution, apoptosis, autophagy, and mitochondrial metabolic/cell redox state. The results obtained indicate that both total and fractionated extracts are potent inhibitors of TNBC cell viability and growth, acting through both an impairment of cell cycle progression and mitochondrial transmembrane potential and a stimulation of cellular autophagy, as demonstrated by the increase of the acidic vesicular organelles and of the intracellular protein markers beclin-1, and total LC3 and LC3-II upon early exposure to the preparations. Identification of the water-soluble bioactive component(s) present in the extract merit further investigation aiming to develop novel prevention and/or treatment agents efficacious against highly metastatic breast carcinomas.
Figure 1. A specimen of Holoturia tubulosa sea cucumber.
Figure 5. Representative flow cytometric analyses of the transmembrane mitochondrial potential (MMP) in control (A,E), total extract- (C,G), and 10K fraction-treated (D,H) MDA-MB231 cells for 24 (A–D) and 48 h (E–H). Dot plots (B) and (F) show the parallel positive controls of valinomycin-treated cells. The values indicated in the bottom quadrants in each frame quantitate the percentage of low red-emitting cells that underwent dissipation of MMP. The results are expressed as mean ± s.e.m. of triplicate assays.
Figure 6. Representative plots showing reactive oxygen species (ROS) accumulation in gated alive MDA-MB231 cells exposed to total extracts (A,C) and 10K fractions (B,D) for 24 (A,C) and 48 h (B,D), compared to controls and H2O2-treated cells as positive controls. The x-axis reports the intensity of green fluorescence emitted by the dye 2’,7’-dichlorodihydrofluorescein, which is proportional to the amount of cytosolic ROS.
Figure 7. Representative flow cytometric analyses of control (A,D), total extract- (B,E), and 10K fraction-treated (C,F) MDA-MB231 cells stained with acridine orange for evaluation of acidic vesicular organelle (AVO) accumulation after 24 (A–C) and 48 h (D,F) of exposure. The percentage indicated in the top quadrants refers to the high red fluorescence-emitting events. The results are expressed as mean ± s.e.m. of triplicate assays.
Aysola,
Triple Negative Breast Cancer - An Overview.
2013, Pubmed
Aysola,
Triple Negative Breast Cancer - An Overview.
2013,
Pubmed
Baharara,
Apoptosis inducing capacity of Holothuria arenicola in CT26 colon carcinoma cells in vitro and in vivo.
2016,
Pubmed
,
Echinobase
Bahrami,
Distribution of Saponins in the Sea Cucumber Holothuria lessoni; the Body Wall Versus the Viscera, and Their Biological Activities.
2018,
Pubmed
,
Echinobase
Biel,
Mitochondrial dysfunction activates lysosomal-dependent mitophagy selectively in cancer cells.
2018,
Pubmed
Bordbar,
High-value components and bioactives from sea cucumbers for functional foods--a review.
2011,
Pubmed
,
Echinobase
Brancaccio,
Sulfur-containing histidine compounds inhibit γ-glutamyl transpeptidase activity in human cancer cells.
2019,
Pubmed
Bray,
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
2018,
Pubmed
Castellano,
On ovothiol biosynthesis and biological roles: from life in the ocean to therapeutic potential.
2018,
Pubmed
Chang,
Effect of bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 on cell cycle arrest, apoptotic and autophagic pathway in triple-negative breast adenocarcinoma MDA-MB-231 cells: An in vitro study.
2018,
Pubmed
Chao,
Orchestration of DNA Damage Checkpoint Dynamics across the Human Cell Cycle.
2017,
Pubmed
Correia-da-Silva,
Anticancer and cancer preventive compounds from edible marine organisms.
2017,
Pubmed
,
Echinobase
Cosse,
BNIP3 protects HepG2 cells against etoposide-induced cell death under hypoxia by an autophagy-independent pathway.
2010,
Pubmed
Eng,
A novel quantitative flow cytometry-based assay for autophagy.
2010,
Pubmed
Garbar,
Chemotherapy treatment induces an increase of autophagy in the luminal breast cancer cell MCF7, but not in the triple-negative MDA-MB231.
2017,
Pubmed
Gartel,
A new method for determining the status of p53 in tumor cell lines of different origin.
2003,
Pubmed
Gonzalez,
Atg7- and Keap1-dependent autophagy protects breast cancer cell lines against mitoquinone-induced oxidative stress.
2014,
Pubmed
Guo,
Inhibiting autophagy increases epirubicin's cytotoxicity in breast cancer cells.
2016,
Pubmed
Guo,
Synergistic effect of eicosapentaenoic acid-enriched phospholipids and sea cucumber saponin on orotic acid-induced non-alcoholic fatty liver disease in rats.
2018,
Pubmed
,
Echinobase
Guo,
Tetrandrine-Induced Autophagy in MDA-MB-231 Triple-Negative Breast Cancer Cell through the Inhibition of PI3K/AKT/mTOR Signaling.
2019,
Pubmed
Gurtner,
Mutant p53-induced up-regulation of mitogen-activated protein kinase kinase 3 contributes to gain of function.
2010,
Pubmed
He,
Regulation mechanisms and signaling pathways of autophagy.
2009,
Pubmed
He,
Establish a flow cytometric method for quantitative detection of Beclin-1 expression.
2013,
Pubmed
Herencia,
Anti-inflammatory activity in mice of extracts from Mediterranean marine invertebrates.
1998,
Pubmed
,
Echinobase
Huovinen,
Characterization of human breast cancer cell lines for the studies on p53 in chemical carcinogenesis.
2011,
Pubmed
Janakiram,
Sea Cucumbers Metabolites as Potent Anti-Cancer Agents.
2015,
Pubmed
,
Echinobase
Kareh,
Anti-proliferative and anti-inflammatory activities of the sea cucumber Holothuria polii aqueous extract.
2018,
Pubmed
,
Echinobase
Khotimchenko,
Pharmacological Potential of Sea Cucumbers.
2018,
Pubmed
,
Echinobase
Klionsky,
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
2016,
Pubmed
Librizzi,
Cytotoxic effects of Jay Amin hydroxamic acid (JAHA), a ferrocene-based class I histone deacetylase inhibitor, on triple-negative MDA-MB231 breast cancer cells.
2012,
Pubmed
Librizzi,
Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells.
2016,
Pubmed
Longo,
Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Negative MDA-MB231 Breast Cancer Cells.
2015,
Pubmed
Luparello,
Cytotoxic Activity of the Histone Deacetylase 3-Selective Inhibitor Pojamide on MDA-MB-231 Triple-Negative Breast Cancer Cells.
2019,
Pubmed
Luparello,
Midregion parathyroid hormone-related protein inhibits growth and invasion in vitro and tumorigenesis in vivo of human breast cancer cells.
2001,
Pubmed
Mizushima,
How to interpret LC3 immunoblotting.
2007,
Pubmed
Nel,
Modes of cell death induced by tetrahydroisoquinoline-based analogs in MDA-MB-231 breast and A549 lung cancer cell lines.
2018,
Pubmed
Pangestuti,
Medicinal and health benefit effects of functional sea cucumbers.
2018,
Pubmed
,
Echinobase
Russo,
Ovothiol isolated from sea urchin oocytes induces autophagy in the Hep-G2 cell line.
2014,
Pubmed
,
Echinobase
Saraiva,
How many diseases is triple negative breast cancer: the protagonism of the immune microenvironment.
2017,
Pubmed
Schillaci,
Immune mediators of sea-cucumber Holothuria tubulosa (Echinodermata) as source of novel antimicrobial and anti-staphylococcal biofilm agents.
2013,
Pubmed
,
Echinobase
Tanida,
Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy.
2005,
Pubmed
Tasdemir,
Cell cycle-dependent induction of autophagy, mitophagy and reticulophagy.
2007,
Pubmed
Tian,
CLE-10 from Carpesium abrotanoides L. Suppresses the Growth of Human Breast Cancer Cells (MDA-MB-231) In Vitro by Inducing Apoptosis and Pro-Death Autophagy Via the PI3K/Akt/mTOR Signaling Pathway.
2019,
Pubmed
Toton,
Beclin-1 and its role as a target for anticancer therapy.
2014,
Pubmed
Vazzana,
Cytotoxic activity of Holothuria tubulosa (Echinodermata) coelomocytes.
2018,
Pubmed
,
Echinobase
Wen,
Chemical composition and nutritional quality of sea cucumbers.
2010,
Pubmed
,
Echinobase
Wijesinghe,
Anticancer activity and mediation of apoptosis in human HL-60 leukaemia cells by edible sea cucumber (Holothuria edulis) extract.
2013,
Pubmed
,
Echinobase
Yang,
Structural analysis and anticoagulant activities of two sulfated polysaccharides from the sea cucumber Holothuria coluber.
2018,
Pubmed
,
Echinobase
Yang,
Sulforaphane induces autophagy by inhibition of HDAC6-mediated PTEN activation in triple negative breast cancer cells.
2018,
Pubmed
Yin,
Autophagy: machinery and regulation.
2016,
Pubmed
Yun,
The Roles of Autophagy in Cancer.
2018,
Pubmed
Zheng,
Phospholipase D couples survival and migration signals in stress response of human cancer cells.
2006,
Pubmed
