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Mar Drugs
2024 Jun 26;227:. doi: 10.3390/md22070292.
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The Composition of Triterpene Glycosides in the Sea Cucumber Psolus peronii: Anticancer Activity of the Glycosides against Three Human Breast Cancer Cell Lines and Quantitative Structure-Activity Relationships (QSAR).
Silchenko AS
,
Kalinovsky AI
,
Avilov SA
,
Popov RS
,
Chingizova EA
,
Menchinskaya ES
,
Zelepuga EA
,
Tabakmakher KM
,
Stepanov VG
,
Kalinin VI
.
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Eight sulfated triterpene glycosides, peronioside A (1) and psolusosides A (2), B (3), G (4), I (5), L (6), N (7) and P (8), were isolated from the sea cucumber Psolus peronii. Peronioside A (1) is a new glycoside, while compounds 2-8 were found previously in Psolus fabricii, indicating the phylogenetic and systematic closeness of these species of sea cucumbers. The activity of 1-8 against human erythrocytes and their cytotoxicity against the breast cancer cell lines MCF-7, T-47D and triple-negative MDA-MB-231 were tested. The most active against cancer cell compounds, psolusosides A (2) and L (6), which were not cytotoxic to the non-transformed cells of the mammary gland, were chosen to study the inhibition of the migration, formation and growth of colonies of the cancer cell lines. Glycoside 2 effectively inhibited the growth of colonies and the migration of the MDA-MB-231 cell line. Compound 6 blocked the growth of colonies of T-47D cells and showed a pronounced antimigration effect on MDA-MB-231 cells. The quantitative structure-activity relationships (QSAR) indicated the strong impact on the activity of the form and size of the molecules, which is connected to the length and architecture of the carbohydrate chain, the distribution of charge on the molecules' surface and various aspects of hydrogen bond formation, depending on the quantity and positions of the sulfate groups. The QSAR calculations were in good accordance with the observed SAR tendencies.
Figure 1. Chemical structures of glycosides isolated from Psolus peronii:
1—peronioside A; 2—psolusoside A; 3—psolusoside B; 4—psolusoside G; 5—psolusoside I; 6—psolusoside L; 7—psolusoside N; 8—psolusoside P.
Figure 2. Morphological differences of P. fabricii and P. peronii. (A)—dorsal and lateral view of P. fabricii; (B)—dorsal and lateral view of P. peronii; (C)—the ossicles of P. fabricii; (D)—the ossicles of P. peronii. Photos by Stepanov V.G.
Figure 3. Cytotoxic effect of glycosides against breast cancer cells: (A) psolusoside A (2) against MCF-7, MDA-MB-231, T-47D, MCF-10A cells; (B) psolusoside L (6) against MCF-7, MDA-MB-231, T-47D, MCF-10A cells for 24 h, 48 h and 72 h. All experiments were carried out in triplicate. The data are presented as means ± SEM.
Figure 4. The number of MCF-7 (A), MDA-MB-231 (B) and T-47D (C) cell colonies under the treatment with different concentrations of psolusosides A (2) and L (6). Data are presented as means ± SEM. * p value ≤ 0.05 considered significant.
Figure 5. Migration of MCF-7 (A,B) and MDA-MB-231 (C,D) cells into wound areas observed with real-time live cell imaging system Juli Stage: (A) 0, 24, and 48 h for MCF-7 cells after treatment with concentrations of 1 and 2 μM of psolusosides A (2) and L (6). (B) Time-course curves of MCF-7 cell migration into the wound area. (C) 0, 6 and 12 h for MDA-MB-231 cells after treatment with concentrations of 1 and 2 μM of psolusosides A (2) and L (6). (D) Time-course curves of MDA-MB-231 cell migration into the wound area. All experiments were carried out in triplicate. The data are presented as means ± SEM.
Figure 6. Three-dimensional plot of hemolytic activity (pIC50) dependence on the principal component values (PCA1—PCA3) calculated for 21 conformational forms of nine glycosides (1–8 and DS-psolusoside B). The glycosides demonstrating hemolytic activity with IC50 ≤ 10 µM were outlined as active and are marked in red, while the rest are marked in violet.
Figure 7. The charge distribution on the molecular surface of glycosides from sea cucumber P. peronii. Molecular surfaces are presented as a contour and colored according to the charge distribution (positive is blue, negative is red). Molecular structures are presented as sticks: (a)—psolusoside A (2); (b)—psolusoside G (4); (c)—psolusoside L (6); (d)—peronioside A (1); (e)—psolusoside B (3); (f)—psolusoside N (7).
