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Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction.

Roel M, Rubiolo JA, Ternon E, Thomas OP, Vieytes MR, Botana LM - Mar Drugs (2015)

Bottom Line: Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study.Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities.The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela (USC), Campus Lugo, 27002 Lugo, Spain. maria.roel@usc.es.

ABSTRACT
The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities.

No MeSH data available.


Related in: MedlinePlus

(A) Heat map of the differentially expressed (DE) mRNAs coding for proteins involved in cell cycle regulation in HepG2 cells treated with 1 μM, 5 μM and 10 μM crambescin C1 (CC1) with respect to control cells. Green color represents mRNA down-regulation of treated cells with respect to controls; (B) Centroid graph for down-regulated genes showed in A. * Significant differences with respect to controls and 5 μM treated cells, p < 0.05, n = 3; (C) Quantification of the cell population percentages in each phase of the cell cycle in control and HepG2 cells treated with 0.3 μM, 1 μM, 5 μM and 10 μM CC1 for 24 h. (p < 0.01, n = 2); (D) Analysis of the relative fluorescence intensity of the stained nuclei. Histograms indicate the differences in the relative proportions of cells in G0/G1 and G2/M phases between control and 10 μM CC1 treated cells.
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marinedrugs-13-04633-f005: (A) Heat map of the differentially expressed (DE) mRNAs coding for proteins involved in cell cycle regulation in HepG2 cells treated with 1 μM, 5 μM and 10 μM crambescin C1 (CC1) with respect to control cells. Green color represents mRNA down-regulation of treated cells with respect to controls; (B) Centroid graph for down-regulated genes showed in A. * Significant differences with respect to controls and 5 μM treated cells, p < 0.05, n = 3; (C) Quantification of the cell population percentages in each phase of the cell cycle in control and HepG2 cells treated with 0.3 μM, 1 μM, 5 μM and 10 μM CC1 for 24 h. (p < 0.01, n = 2); (D) Analysis of the relative fluorescence intensity of the stained nuclei. Histograms indicate the differences in the relative proportions of cells in G0/G1 and G2/M phases between control and 10 μM CC1 treated cells.

Mentions: As initially determined by MTT, CC1 inhibits cell proliferation. Microarrays results showed that CC1 negatively affected the cell cycle progression down-regulating the expression of cyclins A, B, D, and E (Figure 5A,B). According to this, a G0/G1 arrest could be expected.


Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction.

Roel M, Rubiolo JA, Ternon E, Thomas OP, Vieytes MR, Botana LM - Mar Drugs (2015)

(A) Heat map of the differentially expressed (DE) mRNAs coding for proteins involved in cell cycle regulation in HepG2 cells treated with 1 μM, 5 μM and 10 μM crambescin C1 (CC1) with respect to control cells. Green color represents mRNA down-regulation of treated cells with respect to controls; (B) Centroid graph for down-regulated genes showed in A. * Significant differences with respect to controls and 5 μM treated cells, p < 0.05, n = 3; (C) Quantification of the cell population percentages in each phase of the cell cycle in control and HepG2 cells treated with 0.3 μM, 1 μM, 5 μM and 10 μM CC1 for 24 h. (p < 0.01, n = 2); (D) Analysis of the relative fluorescence intensity of the stained nuclei. Histograms indicate the differences in the relative proportions of cells in G0/G1 and G2/M phases between control and 10 μM CC1 treated cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556997&req=5

marinedrugs-13-04633-f005: (A) Heat map of the differentially expressed (DE) mRNAs coding for proteins involved in cell cycle regulation in HepG2 cells treated with 1 μM, 5 μM and 10 μM crambescin C1 (CC1) with respect to control cells. Green color represents mRNA down-regulation of treated cells with respect to controls; (B) Centroid graph for down-regulated genes showed in A. * Significant differences with respect to controls and 5 μM treated cells, p < 0.05, n = 3; (C) Quantification of the cell population percentages in each phase of the cell cycle in control and HepG2 cells treated with 0.3 μM, 1 μM, 5 μM and 10 μM CC1 for 24 h. (p < 0.01, n = 2); (D) Analysis of the relative fluorescence intensity of the stained nuclei. Histograms indicate the differences in the relative proportions of cells in G0/G1 and G2/M phases between control and 10 μM CC1 treated cells.
Mentions: As initially determined by MTT, CC1 inhibits cell proliferation. Microarrays results showed that CC1 negatively affected the cell cycle progression down-regulating the expression of cyclins A, B, D, and E (Figure 5A,B). According to this, a G0/G1 arrest could be expected.

Bottom Line: Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study.Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities.The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela (USC), Campus Lugo, 27002 Lugo, Spain. maria.roel@usc.es.

ABSTRACT
The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities.

No MeSH data available.


Related in: MedlinePlus