Asterosaponins are a class of steroid oligoglycosides isolated from starfish with characteristic structures and diverse biological activities. In this review, we have attempted to combine the most important data concerning asterosaponins and give a list of these secondary metabolites with their structural peculiarities. The purpose of this review is to provide a brief but as complete as possible principal information about their chemical structures, taxonomic distribution in the marine environment, distribution in different geographical areas and depths, some properties, biological activities, and functions. Some other rare steroid metabolites from starfish, closely related in structures and probably biogenesis to asterosaponins, are also discussed.

Malignant melanoma is the most dangerous form of skin cancer, with a rapidly increasing incidence rate. Despite recent advances in melanoma research following the approval of several novel targeted and immuno-therapies, the majority of oncological patients will ultimately perish from the disease. Thus, new effective drugs are still required. Starfish steroid glycosides possess different biological activities, including antitumor activity. The current study focused on the determination of the in vitro inhibitory activity and the mechanism of action of cyclic steroid glycosides isolated from the starfish Echinaster luzonicus—luzonicoside A (LuzA) and luzonicoside D (LuzD)—in human melanoma RPMI-7951 and SK-Mel-28 cell lines. LuzA inhibited proliferation, the formation of colonies, and the migration of SK-Mel-28 cells significantly more than LuzD. Anti-cancer activity has been ascribed to cell cycle regulation and apoptosis induction. The molecular mechanism of action appears to be related to the regulation of the activity of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP), along with Survivin, Bcl-2, p21 and cyclin D1 level. Overall, our findings support a potential anti-cancer efficacy of luzonicosides A and D on human melanoma cells.

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.

New asterosaponin, acanthaglycoside G (1), along with three previously known steroidal oligoglycosides (2‒4), were isolated from the ethanolic extract of the starfish Acanthaster planci, collected off the coast of Vietnam. The structure of 1 was mainly elucidated by extensive NMR and ESIMS techniques as sodium 6-O-{β-D-fucopyranosyl-(1→2)-β-D-quinovopyranosyl-(1→4)-[β-D-quinovopyranosyl-(1→2)]-β-D-quinovopyranosyl-(1→3)-β-D-quinovopyranosyl}-6α-hydroxy-5α-pregn-9(11)-en-20-one-3β-yl sulfate. Compounds 3 and 4 showed slight cytotoxic activities against cancer RPMI-7951, HT-29, and MDA-MB-231 cell lines, but effectively inhibited in non-toxic concentrations colony formation of HT-29 and MDA-MB-231 cells and cell migration of MDA-MB-231 cells. Compounds 1 and 2 were inactive or less active, respectively.

The neuritogenic and neuroprotective activities of six starfish polar steroids, asterosaponin Р₁, (25S)-5α-cholestane-3β,4β,6α,7α,8,15α,16β,26-octaol, and (25S)-5α-cholestane-3β,6α,7α,8,15α,16β,26-heptaol (1–3) from the starfish Patiria pectinifera and distolasterosides D₁–D₃ (4–6) from the starfish Distolasterias nipon were analyzed using the mouse neuroblastoma (NB) C-1300 cell line and an organotypic rat hippocampal slice culture (OHSC). All of these compounds enhanced neurite outgrowth in NB cells. Dose-dependent responses to compounds 1–3 were observed within the concentration range of 10–100 nM, and dose-dependent responses to glycosides 4–6 were observed at concentrations of 1–50 nM. All the tested substances exhibited notable synergistic effects with trace amounts of nerve growth factor (NGF, 1 ng/mL) or brain-derived neurotrophic factor (BDNF, 0.1 ng/mL). Using NB cells and OHSCs, it was shown for the first time that starfish steroids 1–6 act as neuroprotectors against oxygen-glucose deprivation (OGD) by increasing the number of surviving cells. Altogether, these results suggest that neurotrophin-like neuritogenic and neuroprotective activities are most likely common properties of starfish polyhydroxysteroids and the related glycosides, although the magnitude of the effect depended on the particular compound structure.