Anti-Hepatocellular Carcinoma (HepG2) Activities of Monoterpene Hydroxy Lactones Isolated from the Marine Microalga Tisochrysis Lutea

Abstract

Tisochrysis lutea is a marine haptophyte rich in omega-3 polyunsaturated fatty acids (e.g., docosahexaenoic acid (DHA)) and carotenoids (e.g., fucoxanthin). Because of the nutraceutical applications of these compounds, this microalga is being used in aquaculture to feed oyster and shrimp larvae. In our earlier report, T. lutea organic crude extracts exhibited in vitro cytotoxic activity against human hepatocarcinoma (HepG2) cells. However, so far, the compound(s) accountable for the observed bioactivity have not been identified. Therefore, the aim of this study was to isolate and identify the chemical component(s) responsible for the bioactivity observed. Bioassay-guided fractionation through a combination of silica-gel column chromatography, followed by preparative thin layer chromatography (PTLC), led to the isolation of two diastereomers of a monoterpenoid lactone, namely, loliolide (1) and epi-loliolide (2), isolated for the first time in this species. The structural elucidation of both compounds was carried out by GC-MS and 1D (1H and 13C APT) and 2D (COSY, HMBC, HSQC-ed, and NOESY) NMR analysis. Both compounds significantly reduced the viability of HepG2 cells and were considerably less toxic towards a non-tumoral murine stromal (S17) cell line, although epi-loliolide was found to be more active than loliolide.

Loliolide, a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum

“…Sub-fraction F6 afforded the monoterpene lactone Loliolide, the structure of which was established by nuclear magnetic resonance (NMR) spectroscopy. The obtained 13 C and 1 H chemical shifts and structural assignments (Table 2) are in accordance with the literature [38].…”

The Medicinal Halophyte Frankenia laevis L. (Sea Heath) Has In Vitro Antioxidant Activity, α-Glucosidase Inhibition, and Cytotoxicity towards Hepatocarcinoma Cells

“…To the best of our knowledge, this is the first report on the in vitro anti-hepatocarcinoma potential of Frankenia species. However, the monoterpene metabolites detected in higher abundance in the dichloromethane extract from F. laevis aerial parts, such as isololiolide and loliolide ( Figure 2 ), have already been isolated from marine macro- and microalgae, respectively, and were ascribed with selective cytotoxicity against HepG2 cells [ 46 , 47 ].…”

Cervical anticancer activities of Annona squamosa Linn. leaf isolate

“…Similarly, Grabarczyk et al [55] stated that loliolide compounds extracted from the Opisthobranch genus were able to inhibit the growth of human nasopharyngeal carcinoma KB (tumor cells of human nasopharyngeal carcinoma KB) and P-388 murine lymphocytic leukemia tumor cells. Loliolide and epi-loliolide compounds have inhibitory activities on the growth of human hepatocarcinoma (HepG-2) cells [56]. Furthermore, Elsayed et al [57] stated that a mixture of fatty acids containing linolenic acid from Egyptian beebread has antibacterial activities against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and PC-3 as well as HepG-2 cancer cells.…”