Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
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.
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.
Abbas,
p21 in cancer: intricate networks and multiple activities.
2009, Pubmed
Abbas,
p21 in cancer: intricate networks and multiple activities.
2009,
Pubmed
Borowicz,
The soft agar colony formation assay.
2015,
Pubmed
Chambers,
Dissemination and growth of cancer cells in metastatic sites.
2002,
Pubmed
Cheng,
Asterosaponin 1, a cytostatic compound from the starfish Culcita novaeguineae, functions by inducing apoptosis in human glioblastoma U87MG cells.
2007,
Pubmed
,
Echinobase
Dong,
Chemical constituents and bioactivities of starfish.
2011,
Pubmed
,
Echinobase
Dyshlovoy,
Proteomic profiling of germ cell cancer cells treated with aaptamine, a marine alkaloid with antiproliferative activity.
2012,
Pubmed
Dyshlovoy,
Mycalamide A shows cytotoxic properties and prevents EGF-induced neoplastic transformation through inhibition of nuclear factors.
2012,
Pubmed
Dyshlovoy,
Activity of aaptamine and two derivatives, demethyloxyaaptamine and isoaaptamine, in cisplatin-resistant germ cell cancer.
2014,
Pubmed
Ivanchina,
Two new asterosaponins from the Far Eastern starfish Lethasterias fusca.
2012,
Pubmed
,
Echinobase
Ivanchina,
Steroid glycosides from marine organisms.
2011,
Pubmed
Jin,
Overview of cell death signaling pathways.
2005,
Pubmed
Kicha,
Cyclic Steroid Glycosides from the Starfish Echinaster luzonicus: Structures and Immunomodulatory Activities.
2015,
Pubmed
,
Echinobase
Kicha,
Two new asterosaponins, archasterosides A and B, from the Vietnamese starfish Archaster typicus and their anticancer properties.
2010,
Pubmed
,
Echinobase
Kicha,
Four new asterosaponins, hippasteriosides A - D, from the Far Eastern starfish Hippasteria kurilensis.
2011,
Pubmed
,
Echinobase
Lazebnik,
Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE.
1994,
Pubmed
Ma,
Polyhydroxysteroidal glycosides from the starfish Anthenea chinensis.
2010,
Pubmed
,
Echinobase
Malyarenko,
Cariniferosides A-F and other steroidal biglycosides from the starfish Asteropsis carinifera.
2012,
Pubmed
,
Echinobase
Malyarenko,
Four New Sulfated Polar Steroids from the Far Eastern Starfish Leptasterias ochotensis: Structures and Activities.
2016,
Pubmed
,
Echinobase
Malyarenko,
Asterosaponins from the Far Eastern starfish Leptasterias ochotensis and their anticancer activity.
2015,
Pubmed
,
Echinobase
Minale,
Steroidal oligoglycosides and polyhydroxysteroids from echinoderms.
1993,
Pubmed
Norbury,
Animal cell cycles and their control.
1992,
Pubmed
Schumacher,
Gold from the sea: marine compounds as inhibitors of the hallmarks of cancer.
2011,
Pubmed
Sternlicht,
How matrix metalloproteinases regulate cell behavior.
2002,
Pubmed
Thao,
Asterosaponins from the Starfish Astropecten monacanthus suppress growth and induce apoptosis in HL-60, PC-3, and SNU-C5 human cancer cell lines.
2014,
Pubmed
,
Echinobase
Tian,
Saponins: the potential chemotherapeutic agents in pursuing new anti-glioblastoma drugs.
2014,
Pubmed
,
Echinobase
Vishchuk,
Sulfated polysaccharides from brown seaweeds Saccharina japonica and Undaria pinnatifida: isolation, structural characteristics, and antitumor activity.
2012,
Pubmed
Vishchuk,
The fucoidans from brown algae of Far-Eastern seas: anti-tumor activity and structure-function relationship.
2014,
Pubmed
Vishchuk,
PDZ-binding kinase/T-LAK cell-originated protein kinase is a target of the fucoidan from brown alga Fucus evanescens in the prevention of EGF-induced neoplastic cell transformation and colon cancer growth.
2017,
Pubmed
Wong,
Apoptosis in cancer: from pathogenesis to treatment.
2012,
Pubmed
Ye,
Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells.
2008,
Pubmed
Zhao,
Asterosaponin 1 induces endoplasmic reticulum stress-associated apoptosis in A549 human lung cancer cells.
2012,
Pubmed
,
Echinobase
Zhou,
Novaeguinoside II inhibits cell proliferation and induces apoptosis of human brain glioblastoma U87MG cells through the mitochondrial pathway.
2011,
Pubmed
,
Echinobase