Malyarenko TV et al. (2018), In Vitro Anticancer and Proapoptotic Activities...

ECB-ART-46727

Mar Drugs 2018 Nov 01;1611:. doi: 10.3390/md16110420.

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In Vitro Anticancer and Proapoptotic Activities of Steroidal Glycosides from the Starfish Anthenea aspera.

Malyarenko TV , Malyarenko OS , Kicha AA , Ivanchina NV , Kalinovsky AI , Dmitrenok PS , Ermakova SP , Stonik VA .

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New marine glycoconjugates-the steroidal glycosides designated as anthenosides V⁻X (1⁻3)-and the seven previously known anthenosides E (4), G (5), J (6), K (7), S1 (8), S4 (9), and S6 (10) were isolated from the extract of the tropical starfish Anthenea aspera. The structures of 1⁻3 were elucidated by extensive NMR and ESIMS techniques. Glycoside 1 contains a rare 5α-cholest-8(14)-ene-3α,7β,16α-hydroxysteroidal nucleus. Compounds 2 and 3 were isolated as inseparable mixtures of epimers. All investigated compounds (1⁻10) at nontoxic concentrations inhibited colony formation of human melanoma RPMI-7951, breast cancer T-47D, and colorectal carcinoma HT-29 cells to a variable degree. The mixture of 6 and 7 possessed significant anticancer activity and induced apoptosis of HT-29 cells. The molecular mechanism of the proapoptotic action of this mixture was shown to be associated with the regulation of anti- and proapoptotic protein expression followed by the activation of initiator and effector caspases.

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Species referenced: Echinodermata
Genes referenced: bax LOC590297 LOC594261 taf12

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	Figure 1. The structures of new compounds 1â€“10 isolated from Anthenea aspera.
	Figure 2. (A) 1H-1H COSY and key HMBC correlations for compound 1. (B) Key ROESY correlations for compound 1.
	Figure 3. The effects of anthenosides 1â€“10 on colony formation of human melanoma, breast cancer, and colorectal carcinoma cells and on induction of apoptosis of HT-29 cells. RPMI-7951 (A), T-47D (B), and HT-29 (C) cells (2.4 Ã— 104/mL) treated with/without the investigated compounds (40 ÂµM) or cisplatin (1 ÂµM) (positive control) were exposed to 1 mL of 0.3% Basal Medium Eagle (BME) agar containing 10% FBS and overlaid with 3.5 mL of 0.5% BME agar containing 10% FBS. The culture was maintained at 37 Â°C in a 5% CO2 atmosphere for 2 weeks. The colonies were counted under a microscope with the aid of the ImageJ software program. The significant differences were evaluated using Studentâ€™s t test. The asterisks indicate a significant decrease in colony formation of cancer cells treated with the tested compounds or cisplatin compared to the non-treated cells (control), * p < 0.05, p < 0.01, * p < 0.001. (D) Regulation of anti- and proapoptotic protein expression, as well as initiator and effector caspase activity, by the mixture of anthenosides J (6) and K (7) in HT-29 cells. HT-29 cells were either treated by cisplatin (1 ÂµM) or the mixture of 6 + 7 (10, 20, and 40 ÂµM) for 24 h. After drug treatment, total protein lysates were prepared. The protein samples (30 Âµg) were subjected to SDS-PAGE, followed by detection with immunoblotting using antibodies against Bcl-XL (30 kDa), Bax (20 kDa), Bak (25 kDa), caspase-9 (45 kDa) and -3 (35 kDa), cleaved caspase-3 (17, 19 kDa), and b-actin (40 kDa) proteins. (E) Relative band intensity was measured using Image Labâ„¢ Software (â€œBio Radâ€, Hercules, CA, USA). The quantitative results are presented as the mean value from three independent experiments. The significant differences were evaluated using Studentâ€™s t test. The asterisks indicate a significant alteration of the proteinsâ€™ expression in cells treated by cisplatin or the mixture of 6 + 7 compared with the non-treated cells (control), * p < 0.05, p < 0.01, * p < 0.001.

References [+] :

Akl, A dual role for the anti-apoptotic Bcl-2 protein in cancer: mitochondria versus endoplasmic reticulum. 2014, Pubmed