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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) MT-1, -2 detection by confocal microscopy in control and HepG2 cells treated with 2.5 μM and 5 μM crambescin C1 (CC1) for 12 h. Representative photos of control and treated cells are shown. Hoechst 33258 was used for nuclei counterstaining (blue) and quantification of nuclear metallothioneins (MTs). Arrows: MTs translocation to the nucleus in treated cells; (B) Quantification of the variations caused by CC1 in the levels of nuclear MTs.
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marinedrugs-13-04633-f007: (A) MT-1, -2 detection by confocal microscopy in control and HepG2 cells treated with 2.5 μM and 5 μM crambescin C1 (CC1) for 12 h. Representative photos of control and treated cells are shown. Hoechst 33258 was used for nuclei counterstaining (blue) and quantification of nuclear metallothioneins (MTs). Arrows: MTs translocation to the nucleus in treated cells; (B) Quantification of the variations caused by CC1 in the levels of nuclear MTs.

Mentions: Increased nuclear concentrations of MTs proteins were observed after treatments with 2.5 μM and 5 μM CC1 when compared with the levels detected in untreated cells. Therefore, CC1 caused the translocation of MTs from cytoplasm to the nucleus (Figure 7A). To quantify this effect, cellular nuclei stained with Hoechst 33258 were delimitated and MTs fluorescence emission analyzed using the Image J software. Results showed significant increases in nuclear MTs levels in response to 2.5 μM and 5 μM CC1 (Figure 7B).


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) MT-1, -2 detection by confocal microscopy in control and HepG2 cells treated with 2.5 μM and 5 μM crambescin C1 (CC1) for 12 h. Representative photos of control and treated cells are shown. Hoechst 33258 was used for nuclei counterstaining (blue) and quantification of nuclear metallothioneins (MTs). Arrows: MTs translocation to the nucleus in treated cells; (B) Quantification of the variations caused by CC1 in the levels of nuclear MTs.
© Copyright Policy
Related In: Results  -  Collection

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

marinedrugs-13-04633-f007: (A) MT-1, -2 detection by confocal microscopy in control and HepG2 cells treated with 2.5 μM and 5 μM crambescin C1 (CC1) for 12 h. Representative photos of control and treated cells are shown. Hoechst 33258 was used for nuclei counterstaining (blue) and quantification of nuclear metallothioneins (MTs). Arrows: MTs translocation to the nucleus in treated cells; (B) Quantification of the variations caused by CC1 in the levels of nuclear MTs.
Mentions: Increased nuclear concentrations of MTs proteins were observed after treatments with 2.5 μM and 5 μM CC1 when compared with the levels detected in untreated cells. Therefore, CC1 caused the translocation of MTs from cytoplasm to the nucleus (Figure 7A). To quantify this effect, cellular nuclei stained with Hoechst 33258 were delimitated and MTs fluorescence emission analyzed using the Image J software. Results showed significant increases in nuclear MTs levels in response to 2.5 μM and 5 μM CC1 (Figure 7B).

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