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SAGE Open Med
2018 Nov 02;6:2050312118809541. doi: 10.1177/2050312118809541.
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Anti-proliferative and anti-inflammatory activities of the sea cucumber Holothuria polii aqueous extract.
Kareh M
,
El Nahas R
,
Al-Aaraj L
,
Al-Ghadban S
,
Naser Al Deen N
,
Saliba N
,
El-Sabban M
,
Talhouk R
.
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Objective: Sea cucumbers are considered among the most important functional foods. Following bioassay guided fractionation, we assessed the anti-proliferative and anti-inflammatory activities of Holothuria polii (H. polii) extracts.
Methods: Sea cucumber ethanolic extract and the partially purified aqueous fractions were assessed for their anti-proliferative activities. These latter bioactivities were evaluated in the highly invasive MDA-MB-231 human breast cancer cells in two-dimensional and three-dimensional cultures using trypan blue exclusion assay. The tumor-suppressive effects of sea cucumber ethanolic extract and aqueous fractions were assayed by measuring the trans-well invasion of MDA-MB-231 cells and the expression of some epithelial mesenchymal transition markers using quantitative reverse-transcription polymerase chain reaction and western blot analysis. The anti-inflammatory activity of the aqueous fraction was tested by measuring the secreted levels of interleukin-6, nitric oxide, and matrix metalloproteinase 9 in endotoxin-induced mammary epithelial SCp2 cells and interleukin-1β in phorbol-12-myristate-13-acetate-activated human monocytic THP-1 cells.
Results: Sea cucumber ethanolic extract and the aqueous fraction significantly decreased the proliferation of MDA-MB-231 cells by more than 50% at similar and noncytotoxic concentrations and caused an arrest in the S-phase of the cell cycle of treated cells. In contrast, petroleum ether, chloroform, ethyl acetate, and n-butanol organic fractions did not show any significant activity. Furthermore, sea cucumber ethanolic extract and aqueous fraction reduced the proliferation of MDA-MB-231 cells in three-dimensional cultures by more than 60% at noncytotoxic concentrations. In addition, treatment with these concentrations resulted in the loss of stellate outgrowths in favor of spherical aggregates and a 30% decrease in invasive properties. Both sea cucumber ethanolic extract and aqueous decreased the transcription of vimentin and the protein expression levels of vimentin and N-cadherin in three-dimensional cultures. The aqueous fraction decreased the levels of inflammatory markers interleukin-6, nitric oxide, and matrix metalloproteinase 9 in the mouse mammary SCp2 cells, and the level of interleukin-1β produced by phorbol-12-myristate-13-acetate-activated THP-1 human monocytic cells.
Conclusion: The data reveal for the first time promising anti-proliferative and anti-inflammatory activities in H. polii water extract in two-dimensional and three-dimensional culture models.
Figure 6. Effect of SCE and Aq treatments on mRNA and protein expression of some
EMT markers in 2D and 3D cultures of MDA-MB-231. (a, b) Bar diagrams
showing the transcript fold change normalized to GAPDH of vimentin in 2D
and 3D cultures, respectively. (c) Western blot showing the protein
expression of vimentin in cntrl versus SCE/Aq-treated lysates from 3D
cultures, with the corresponding densitometric quantification
represented in bar diagrams. (d) Western blot showing the protein
expression of N-cadherin in cntrl versus SCE/Aq-treated lysates from 3D
cultures, with the corresponding densitometric quantification
represented in bar diagrams. GAPDH was used for equal loading.
Figure 7. Effect of Aq and SCE on endotoxin (ET)-induced interleukin-6 (IL-6),
nitric oxide (NO), and matrix metalloproteinase 9 (MMP9) in SCp2 cells
and on ET-induced interleukin 1β (IL-1β) in PMA-activated THP-1 cells.
Cells were treated with 1, 5, and 10 mg/mL of Aq fraction (left panels)
and 1 and 5 mg/mL of SCE (right panels) and media samples were collected
24 h after ET stimulation and analyzed for their (a) IL-6 secretion, (b)
NO production, (c) MMP9 activity, and (d) IL-1β secretion using ELISA
(for IL-6 and IL-1β), Griess reaction assay (for NO), and zymography
(for MMP9 activity). Zymograms were analyzed by gel documentation
(Bio-Rad) using the software Quantity One. Statistical significance is
represented by (*) asterisk indicating significant difference at
p < 0.05
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