In VitroGrowth Inhibitory Activities of Natural Products from Irciniid Sponges against Cancer Cells: A Comparative Study

Abstract

Marine sponges of the Irciniidae family contain both bioactive furanosesterterpene tetronic acids (FTAs) and prenylated hydroquinones (PHQs). Both classes of compounds are known for their anti-inflammatory, antioxidant, and antimicrobial properties and known to display growth inhibitory effects against various human tumor cell lines. However, the different experimental conditions of the reported in vitro bioassays, carried out on different cancer cell lines within separate studies, prevent realistic actual discrimination between the two classes of compounds from being carried out in terms of growth inhibitory effects. In the present work, a chemical investigation of irciniid sponges from Tunisian coasts led to the purification of three known FTAs and three known PHQs. The in vitro growth inhibitory properties of the six purified compounds have been evaluated in the same experiment in a panel of five human and one murine cancer cell lines displaying various levels of sensitivity to proapoptotic stimuli. Surprisingly, FTAs and PHQs elicited distinct profiles of growth inhibitory-responses, differing by one to two orders of magnitude in favor of the PHQs in all cell lines. The obtained comparative results are discussed in the light of a better selection of drug candidates from natural sources.

Ircinia ramosa Sponge Extract (iSP) Induces Apoptosis in Human Melanoma Cells and Inhibits Melanoma Cell Migration and Invasiveness

“…In fact, the IC50 analysis (Figure 1B) showed a value of 199.9 µg/mL (±3.12) for NHEM, whilst for melanoma cancer cells, it was between 20-80 µg/mL, suggesting that the antiproliferative effect of iSP was specific to cancer cells. Since MTT assay is an indirect analytical method to evaluate cell proliferation, we confirmed the antiproliferative effect of iSP by performing a carboxyfluorescein succinimidyl ester (CFSE) assay [16]. In particular, A375 cells were selected, given their lower IC50 value (26.08 ± 5.47) and their aggressive phenotype [25].…”

“…These metabolites were detected by comparing their exact masses with those recorded in databases, e.g., the Dictionary of Natural Products (DNP) and SciFinder based on their fragmentation pattern in the MSMS spectra. Marine sponges belonging the genus Ircinia are known to be a very rich source of terpenoids, which have been found to possess diverse bioactivities [14][15][16]. Hahn et al 2014 [17] reported the isolation of PPARδ agonistic monocyclofarnesol-derived sesquiterpenoids and their hydroxylated analogues from Ircinia sp., including compound 1.…”

“…Different sponge extracts have been demonstrated to induce cell death by activating multiple death pathways, such as apoptosis, autophagy and ferroptosis, in different type of cancer cells, including melanoma [12][13][14]. Among these, marine sponges of the Irciniidae family are known for their antimicrobial and anti-inflammatory activities and have been demonstrated to exert cytotoxic effects on human leukemia, breast and colon cancer cells [14][15][16]. Ircinia ramosa (Keller, 1889) is a prolific producer of biologically active metabolites, such as alkaloids, terpenoids and sterols, that belongs to the family Irciniidae and showed strong inhibitory activity against multiple human cancer cell lines [15].…”

Pharmacological Activities of Extracts and Compounds Isolated from Mediterranean Sponge Sources

“…In another work [ 60 ], three prenylated-hydroquinones ( 15 , 16 , 17 ), in addition to three known furanosesterpene tetronic acids (iricinin 1 ( 19 ), sarcotin A ( 20 ), and variabilin ( 21 )) were purified from three Sarcotragus sponge species that were collected from Tunisian coasts: S. spinosulus from Tabarka and Monastir; S. fasciculatus , collected from Monastir; and S. foetidus collected from Cap Zebib. Comparing the inhibitory activity of the six compounds on viability of a panel of cancer cells with different sensitivity to pro-apoptotic stimuli, the polyprenyl-hydroquinones displayed greater potency than furanosesterpene tetronic acids, and only the hydroxylated polyprenyl-hydroquinone showed IC 50 < 10 M in all cell lines that were tested [ 60 ].…”