Malyarenko OS et al. (2017), The Inhibitory Activity of Luzonicosides from t...

ECB-ART-45633

Mar Drugs 2017 Jul 18;157:. doi: 10.3390/md15070227.

Show Gene links Show Anatomy links

The Inhibitory Activity of Luzonicosides from the Starfish Echinaster luzonicus against Human Melanoma Cells.

Malyarenko OS , Dyshlovoy SA , Kicha AA , Ivanchina NV , Malyarenko TV , Carsten B , Gunhild VA , Stonik VA , Ermakova SP .

???displayArticle.abstract???
Malignant melanoma is the most dangerous form of skin cancer, with a rapidly increasing incidence rate. Despite recent advances in melanoma research following the approval of several novel targeted and immuno-therapies, the majority of oncological patients will ultimately perish from the disease. Thus, new effective drugs are still required. Starfish steroid glycosides possess different biological activities, including antitumor activity. The current study focused on the determination of the in vitro inhibitory activity and the mechanism of action of cyclic steroid glycosides isolated from the starfish Echinaster luzonicus-luzonicoside A (LuzA) and luzonicoside D (LuzD)-in human melanoma RPMI-7951 and SK-Mel-28 cell lines. LuzA inhibited proliferation, the formation of colonies, and the migration of SK-Mel-28 cells significantly more than LuzD. Anti-cancer activity has been ascribed to cell cycle regulation and apoptosis induction. The molecular mechanism of action appears to be related to the regulation of the activity of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP), along with Survivin, Bcl-2, p21 and cyclin D1 level. Overall, our findings support a potential anti-cancer efficacy of luzonicosides A and D on human melanoma cells.

???displayArticle.pubmedLink??? 28718806
???displayArticle.pmcLink??? PMC5532669
???displayArticle.link??? Mar Drugs

Genes referenced: birc5 LOC100893907 LOC115919910 LOC592256 LOC594261 polr3a

???attribute.lit??? ???displayArticles.show???

	Figure 1. Structures of luzonicoside A (LuzA) (1) and luzonicoside D (LuzD) (2) isolated from the starfish E. luzonicus.
	Figure 2. The effect of LuzA and LuzD on human melanoma cell proliferation. (A) Human melanoma cells RPMI-7951 (1 × 104 cells/well) and (B) SK-Mel-28 (1 × 104 cells/well) were seeded in 96-well plates in 200 µL of Dulbecco’s Modified Eagle’s medium (DMEM), then treated with LuzA and LuzD (10, 20, and 40 µM), or their vehicle—DMSO—as a negative control, for 72 h. Cell proliferation was determined by MTS assay. Data are represented as the means ± standard deviation (SD) as determined from triplicate experiments.
	Figure 3. The effect of LuzA and LuzD on cell cycle regulation and the apoptosis induction of human melanoma cells. SK-Mel-28 cells (2 × 105 cells/well) were treated with LuzA (A) and LuzD (B) at doses of 10, 20, and 40 µM for 48 h. Then, cells were harvested with a trypsin-ethylenediaminetetraacetic acid (EDTA) solution, fixed with 70% EtOH/H2O, stained with PI/RNase buffer, and analysed by fluorescence-activated cell sorting (FACS). The results were quantitatively analyzed by Cell Quest Pro software (BD Bioscience, San Jose, CA, USA). The amount of apoptotic cells was detected as a sub-G1 population containing different concentrations of LuzA and LuzD. After 48 h of incubation, cells were harvested with a trypsin-EDTA solution, fixed with 70% EtOH/H2O, stained with PI/RNase buffer, and analysed by FACS. The results were quantitatively analyzed using the Cell Quest Pro software (BD Bioscience, San Jose, CA, USA). The asterisk () indicates a significant increasing of the amount of cells in the cell cycle phase treated with glycosides compared with the non-treated cells ( p < 0.05). (C) The amount of the apoptotic cells was detected as a sub-G1 population. The asterisk () indicates a significant increasing of the amount of apoptotic cells treated with glycosides compared with the non-treated cells ( p < 0.05). (D) The activation of cleaved caspase-3, PARP, cleaved PARP, Survivin, p21, Bcl-2, and Cyclin D1. SK-Mel-28 cells were treated with 10, 20, and 40 µM of LuzA and LuzD and incubated for 48 h. After drug exposure, total protein lysates were prepared. The protein samples (30 µg) were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and followed by detection with immunoblotting, using antibodies against cleaved caspase-3 (19 kDa), PARP (116 kDa), cleaved PARP (89 kDa), Survivin (16.5 kDa), p21 (21 kDa), Bcl-2 (28 kDa), and Cyclin D1 (36 kDa) proteins.

References [+] :

Abbas, p21 in cancer: intricate networks and multiple activities. 2009, Pubmed