Malyarenko TV et al. (2015), Four New Sulfated Polar Steroids from the Far E...

ECB-ART-44126

Mar Drugs 2015 Jul 16;137:4418-35. doi: 10.3390/md13074418.

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Four New Sulfated Polar Steroids from the Far Eastern Starfish Leptasterias ochotensis: Structures and Activities.

Malyarenko TV , Malyarenko Vishchuk OS , Ivanchina NV , Kalinovsky AI , Popov RS , Kicha AA .

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Three new sulfated steroid monoglycosides, leptaochotensosides A-C (1-3), and a new sulfated polyhydroxylated steroid (4) were isolated from the alcoholic extract of the Far Eastern starfish Leptasterias ochotensis. The structures of compounds 1-4 were established by extensive nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESIMS) analyses and chemical transformations. Although the isolated compounds did not show any apparent cytotoxicity against melanoma RPMI-7951 and breast cancer T-47D cell lines, leptaochotensoside A (1) demonstrated inhibition of T-47D cell colony formation in a soft agar clonogenic assay at nontoxic doses. In addition, this compound decreased the epidermal growth factor (EGF)-induced colony formation of mouse epidermal JB6 Cl41 cells. The cancer preventive action of 1 is realized through regulation of mitogen-activated protein kinase (MAPK) signaling pathway.

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Genes referenced: LOC100889782 LOC100893907 LOC105441151 LOC115919910 LOC586799 LOC593824

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	Figure 1. The structures of compounds 1–4 isolated from L. ochotensis.
	Figure 2. (A) 1H-1H Correlation spectroscopy (1H-1H COSY) and key heteronuclear multiple bond connectivity (HMBC) correlations for compound 1; (B) Key nuclear Overhauser effect spectroscopy (NOESY) correlations for compound 1.
	Figure 3. Ex vivo cytotoxicities of leptaochotensosides A–C (1–3) and sulfated polyhydroxysteroid 4. (A) Human melanoma RPMI-7951 cells (8 × 103/well) and (B) breast cancer T-47D cells (8 × 103/well) were incubated with compounds 1–4 (0–200 µM) for 24 h at 37 °C in an 5% CO2 incubator. Compounds cytotoxicities were estimated using MTS assay. Data are represented as the mean ± SD as determined from triplicate experiments.

	Figure 5. The effect of leptaochotensoside A (1) on the epidermal growth factor (EGF)-induced colony formation of JB6 Cl41 cells and molecular mechanism in JB6 Cl41 cells. (A) Leptaochotensoside A (1) inhibits EGF-induced anchorage-independent growth of mouse epidermal JB6 Cl41 cells. JB6 Cl41 cells (8 × 103) were exposed to EGF (10 ng/mL) and treated with 1 (0–200 µM) in 1 mL of 0.3% Basal Medium Eagle (BME) agar containing 10% fetal bovine serum, 2 mM l-glutamine, and 25 µg/mL gentamicin. The cultures were maintained at 37 °C in an 5% CO2 incubator for 14 days, and the cell colonies were scored using a microscope Motic AE 20 (Motic) and the Motic Image Plus computer program. Data are represented as the mean ± SD as determined from triplicate experiments and the asterisks indicate a significant (*** p < 0.001) decrease of the colony formation of the cells treated with leptaochotensoside A (1) compared with the phosphate buffered saline (PBS)-treated group; (B) The absence of cytotoxic effect of leptaochotensoside A (1) on JB6 Cl41 cells. An MTS assay was used after treatment of cells with 1 for 24 h. All the experiments were performed in triplicate, and the mean absorbance values were calculated. Data are represented as the mean ± SD as determined from triplicate experiments; (C) Leptaochotensoside A (1) inhibits MAPK signaling pathway in JB6 Cl41 cells. After cells (6 × 105) were cultured in a 10-cm dish overnight, they were treated with compound 1 (0–200 µM) for 24 h. Then, the cells were starved in serum-free medium for another 12 h and treated with EGF (10 ng/mL) for 15 min. Cells were harvested and protein levels were determined by Western blot analysis.

References [+] :

Barrett, Mechanisms of multistep carcinogenesis and carcinogen risk assessment. 1993, Pubmed