Malyarenko TV et al. (2022), In Vitro Anticancer and Cancer-Preventive Activ...

ECB-ART-50421

Mar Drugs 2022 Mar 20;203:. doi: 10.3390/md20030216.

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In Vitro Anticancer and Cancer-Preventive Activity of New Triterpene Glycosides from the Far Eastern Starfish Solaster pacificus.

Malyarenko TV , Malyarenko OS , Kicha AA , Kalinovsky AI , Dmitrenok PS , Ivanchina NV .

Abstract
Sea stars or starfish (class Asteroidea) and holothurians or sea cucumbers (class Holothuroidea), belonging to the phylum Echinodermata (echinoderms), are characterized by different sets of glycosidic metabolites: the steroid type in starfish and the triterpene type in holothurians. However, herein we report the isolation of eight new triterpene glycosides, pacificusosides D-K (1-3, 5-9) along with the known cucumarioside D (4), from the alcoholic extract of the Far Eastern starfish Solaster pacificus. The isolated new compounds are closely related to the metabolites of sea cucumbers, and their structures of 1-3 and 5-9 were determined by extensive NMR and ESIMS techniques. Compounds 2, 5, and 8 have a new type of tetrasaccharide chain with a terminal non-methylated monosaccharide unit. Compounds 3, 6, and 9 contain another new type of tetrasaccharide chain, having 6-O-SO3-Glc as one of the sugar units. The cytotoxic activity of 1-9 against non-cancerous mouse epidermal cells JB6 Cl41 and human melanoma cell lines SK-MEL-2, SK-MEL-28, and RPMI-7951 was determined by MTS assay. Compounds 1, 3, 4, 6, and 9 showed potent cytotoxicity against these cell lines, but the cancer selectivity (SI > 9) was observed only against the SK-MEL-2 cell line. Compounds 1, 3, 4, 6, and 9 at the non-toxic concentration of 0.1 μM significantly inhibited neoplastic cell transformation of JB6 Cl41 cells induced by chemical carcinogens (EGF, TPA) or ionizing radiation (X-rays and UVB). Moreover, compounds 1 and 4 at the non-toxic concentration of 0.1 µM possessed the highest inhibiting activity on colony formation among the investigated compounds and decreased the colonies number of SK-MEL-2 cells by 64% and 70%, respectively. Thus, triterpene glycosides 1 and 4 can be considered as prospective cancer-preventive and anticancer-compound leaders.

PubMed ID: 35323516
PMC ID: PMC8951750
Article link: Mar Drugs
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	Figure 1. The structures of compounds 1−9 isolated from S. pacificus.
	Figure 2. (A) 1H-1H COSY and key HMBC correlations for compounds 1–3 and 5–9. (B) Key ROESY correlations for compounds 1–3 and 5–9.
	Figure 3. Key ROESY correlations of oligosaccharide moiety for compounds 1–3 and 5–9.
	Figure 4. The effect of the triterpene glycosides 1–9 from S. pacificus on neoplastic cells transformation of JB6 Cl41 induced by chemical carcinogens. JB6 Cl41 cells (2.4 × 104/mL) treated with/without (A) EGF (1 ng/mL) and investigated compound (0.1 µM) or (B) TPA (10 ng/mL) or investigated compound (0.1 µM) in agar mix. 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 (n = 9 for control and each compound; n—quantity of photos). The magnification of representative photos of colonies is ×10. The asterisks (* p < 0.05, p < 0.01, * p < 0.001) indicate a significant decrease of colony formation in cells treated with compound compared with the EGF- or TPA-treated cells.
	Figure 5. The effect of the triterpene glycosides 1–9 from S. pacificus on neoplastic cells transformation of JB6 Cl41 induced by ionizing radiation. JB6 Cl41 cells (2.4 × 104/mL) treated with/without (A) X-rays (0.5 Gy/9 times) and investigated compound (0.1 µM) or (B) UVB (0.3 mJ/cm2) or investigated compound (0.1 µM) in 1 mL of 0.3% basal medium Eagle (BME’s) agar containing 10% FBS and overlaid with 3.5 mL of 0.5% BME’s 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 (n = 9 for control and each compound; n—quantity of photos). The magnification of representative photos of colonies is ×10. The asterisks (* p < 0.05, *** p < 0.001) indicate a significant decrease of colony formation in cells treated with compound compared with the X-ray- or UVB-treated cells.
	Figure 6. The effect of the triterpene glycosides 1–9 from S. pacificus on colony formation of melanoma SK-MEL-2 cells. (A,B) SK-MEL-2 cells (2.4 × 104/mL) treated with/without and investigated compound (0.1 µM) in agar mix. 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 (n = 9 for control and each compound; n—quantity of photos). The magnification of representative photos of colonies is ×10. The asterisks (* p < 0.05, *** p < 0.001) indicate a significant decrease of colony formation in cells treated with compound compared with the X-ray- or UVB-treated cells.

References [+] :

Aminin, Anticancer activity of sea cucumber triterpene glycosides. 2015, Pubmed, Echinobase