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 1–10 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 1–10 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 × 104/mL) treated with/without the investigated compounds (40 µM) or cisplatin (1 µM) (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 °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 Student’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 µM) or the mixture of 6 + 7 (10, 20, and 40 µM) for 24 h. After drug treatment, total protein lysates were prepared. The protein samples (30 µg) 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 Lab™ Software (“Bio Rad”, Hercules, CA, USA). The quantitative results are presented as the mean value from three independent experiments. The significant differences were evaluated using Student’s t test. The asterisks indicate a significant alteration of the proteins’ 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