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Potential use of compounds from sea cucumbers as MDM2 and CXCR4 inhibitors to control cancer cell growth.

ABSTRACT: Ineffectiveness of cancer therapy may originate in the incompatibility of the treatment with various mutations in the cancer cells. Finding novel anticancer treatments that work efficiently for varying types of cancer cells remains challenging. Previous studies have identified that compounds in sea cucumbers are capable of inhibiting the growth of cancer cells and inducing apoptosis. However, information on the underlying mechanisms controlling cancer cell growth at a molecular level remains limited. The current study analyzed the potential of colochiroside A, ds-echinoside A, philinopside E, sphingosine and stichoposide C as inhibitors for anticancer target proteins, including mouse double minute 2 homolog (MDM2) and C-X-C chemokine receptor type 4 (CXCR4). Inhibition of MDM2 triggers apoptosis through regulation of tumor protein 53 and CXCR4 inhibition may prevent cancer cell proliferation and growth by affecting the Janus kinase 2/3 signal transducer and activator of transcription signaling pathway and protein tyrosine kinase 2. The results of a binding affinity analysis using molecular docking revealed that philinopside E and ds-echinoside A may inhibit MDM2 and CXCR4. The data suggested that these active compounds may be promising inhibitors of cell growth by binding to two targets simultaneously. Furthermore, stichoposide C and colochiroside A were predicted to inhibit CXCR4. Additional research is needed to validate the in vitro activity of the aforementioned compounds.

SUBMITTER: Wargasetia TL

PROVIDER: S-EPMC6144067 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Potential use of compounds from sea cucumbers as MDM2 and CXCR4 inhibitors to control cancer cell growth.

Wargasetia Teresa Liliana TL Permana Sofy S Widodo Nashi N

Experimental and therapeutic medicine 20180807 4

Ineffectiveness of cancer therapy may originate in the incompatibility of the treatment with various mutations in the cancer cells. Finding novel anticancer treatments that work efficiently for varying types of cancer cells remains challenging. Previous studies have identified that compounds in sea cucumbers are capable of inhibiting the growth of cancer cells and inducing apoptosis. However, information on the underlying mechanisms controlling cancer cell growth at a molecular level remains lim ...[more]

PMID: 30250516

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Project description:Background:Mono-specific aquaculture effluents contain high concentrations of nutrients and organic matter, which affect negatively the water quality of the recipient ecosystems. A fundamental feature of water quality is its transparency. The fraction of dissolved organic matter that absorbs light is named chromophoric dissolved organic matter (CDOM). A sustainable alternative to mono-specific aquaculture is the multitrophic aquaculture that includes species trophically complementary named "extractive" species that uptake the waste byproducts. Sea cucumbers are recognized as efficient extractive species due to the consumption of particulate organic matter (POM). However, the effects of sea cucumbers on CDOM are still unknown. Methods:During more than one year, we monitored CDOM in two big-volume tanks with different trophic structure. One of the tanks (-holothurian) only contained around 810 individuals of Anemonia sulcata, whereas the other tank (+holothurian) also included 90 individuals of Holothuria tubulosa and Holothuria forskali. We routinely analyzed CDOM absorption spectra and determined quantitative (absorption coefficients at 325 nm) and qualitative (spectral slopes) optical parameters in the inlet waters, within the tanks, and in their corresponding effluents. To confirm the time-series results, we also performed three experiments. Each experiment consisted of two treatments: +holothurians (+H) and -holothurians (-H). We set up three +H tanks with 80 individuals of A. sulcata and 10 individuals of H. tubulosa in each tank and four -H tanks that contained only 80 individuals of A. sulcata. Results:In the time-series, absorption coefficients at 325 nm (a325) and spectral slopes from 275 to 295 nm (S275-295) were significantly lower in the effluent of the +holothurian tank (average: 0.33 m-1 and 16 µm-1, respectively) than in the effluent of the -holothurian tank (average: 0.69 m-1 and 34 µm-1, respectively), the former being similar to those found in the inlet waters (average: 0.32 m-1 and 22 µm-1, respectively). This reduction in the absorption of the dissolved organic matter appears to be mediated by the POM consumption by holothurians. The experiments confirmed the results observed in the time-series. The a325 and S275-295 values were significantly lower in the treatment with holothurians than in the treatment without holothurians indicating a reduction in the concentration of chromophoric organic compounds, particularly of low molecular weight. Discussion:Consequently, sea cucumbers appear to improve water transparency in aquaculture tanks. The underlying mechanism of this improvement might be related to the POM consumption by holothurians, which reduces the concentration of CDOM derived from POM disaggregation or to the direct assimilation of dissolved compounds of low molecular weight as chromophoric amino acids.

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Potential use of compounds from sea cucumbers as MDM2 and CXCR4 inhibitors to control cancer cell growth.

Publications

Potential use of compounds from sea cucumbers as MDM2 and CXCR4 inhibitors to control cancer cell growth.

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