Anti-Proliferative Potential of Secondary Metabolites from the Marine Sponge Theonella sp.: Moving from Correlation toward Causation

Abstract

Marine sponges have been recognized as a rich source of potential anti-proliferative metabolites. Currently, there are two sponge-derived anti-cancer agents (a macrolide and a nucleoside) isolated from the Porifera phylum, suggesting the great potential of this sponge as a rich source for anti-neoplastic agents. To search for more bioactive metabolites from this phylum, we examined the EtOAc extract of Theonella sp. sponge. We isolated seven compounds (1–7), including four 4-methylene sterols (1–4), two nucleosides (5 and 6), and one macrolide (7). Among them, theonellasterol L (1) was identified for the first time, while 5′-O-acetyl-2′-deoxyuridine (5) and 5′-O-acetylthymidine (6) were the first identified deoxyuridine and thymidine derivatives from the sponge Theonella sp. These structures were elucidated based on their spectroscopic data. The anti-proliferation activity of compounds 1–7 against the MCF-7, MDA-MB-231, T-47D, HCT-116, DLD-1, K562, and Molt 4 cancer cell lines was determined. The results indicated that the 14-/15-oxygenated moiety played an important role in the antiproliferative activity and the macrolide derivatives dominated the anti-proliferative effect of the sponge Theonella sp. The in silico analysis, using a chemical global positioning system for natural products (ChemGPS-NP), indicated an anti-proliferative mode of actions (MOA) suggesting the potential applications of the isolated active metabolites as anti-proliferative agents.

Marine natural products

“…465 Other sterols were obtained from Dysidea 1137-1144, Xestospongia 1145, Halichondria 1146-1148, and Echinoclathria 1149 sponges, [465][466][467][468][469] while a new theonellasterol 1150 extends the membership of the 4-methylidene class of sterol commonly found from genus Theonella. 470 An unusual spiro-sterol 1151 was also reported. 415 New stellettin 1152-1157 and rhabdastin 1158 and 1159 triterpenoids came from Stelletta and Rhabdastrella sponges, respectively.…”

Theonella: A Treasure Trove of Structurally Unique and Biologically Active Sterols

“…In 2021, Lai et al reported the isolation of theonellasterol L ( 11 ), together with three known 4-methylene sterols, two nucleosides, and one macrolide ( Figure 2 ). The comparison of the cytotoxic activities of 4-methylene sterols reported in this paper with the previous reported ones showed that only derivatives highly functionalized and especially with oxygenated functions at position C-14 or C-15 are endowed with cytotoxic activity [ 47 ].…”

Antiproliferation Effects of Marine-Sponge-Derived Methanol Extract of Theonella swinhoei in Oral Cancer Cells In Vitro

“…Several extraction studies recently isolated several pure compounds from the marine sponge Theonella swinhoei ( T. swinhoei ) [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. However, most studies [ 17 , 23 ] focused on bioactive compound isolations of the marine sponge T. swinhoei .…”

“…Several extraction studies recently isolated several pure compounds from the marine sponge Theonella swinhoei ( T. swinhoei ) [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. However, most studies [ 17 , 23 ] focused on bioactive compound isolations of the marine sponge T. swinhoei . They provided IC 50 values for certain cancer cell lines such as liver (HepG2) [ 18 ], colon (HCT-16) [ 19 ], lymphoma (P388) [ 20 ], and breast (MCF7 and MDA-MB-231) [ 22 , 23 ] without investigating its antiproliferation mechanism.…”

“…However, most studies [ 17 , 23 ] focused on bioactive compound isolations of the marine sponge T. swinhoei . They provided IC 50 values for certain cancer cell lines such as liver (HepG2) [ 18 ], colon (HCT-16) [ 19 ], lymphoma (P388) [ 20 ], and breast (MCF7 and MDA-MB-231) [ 22 , 23 ] without investigating its antiproliferation mechanism. However, the antiproliferation studies of Theonella natural products were not reported in oral cancer cells and evaluated for their safety in normal cells.…”