Aquaculture Soft Coral Lobophytum crassum as a Producer of Anti-Proliferative Cembranoids

Abstract

Our continuous search for marine bioactive secondary metabolites led to the screening of crude extracts from a variety of aquaculture soft corals. The ethyl acetate (EtOAc) extract of Lobophytum crassum showed a distinctive chemical profile that was different from the wild type. It demonstrated significant anti-proliferative activity against Molt 4 leukemia cell with an IC50 value of 1 μg/mL after 24 h. Chemical investigation focusing on the unique peaks in L. crassum profile led to the discovery of a new α-tocopherol crassumtocopherol C (1), and two new cembrane-based diterpenoids culobophylins D (2) and E (3), along with ten known cembranoids (4–13). The structures of these isolates were elucidated using extensive spectroscopic techniques and a comparison with previously published data of related metabolites. Compound 2 was found to possess the first identified saturated internal C4-O-C14 linkage six-membered ring among all cembrane-type diterpenoids. The anti-proliferative activity of all the isolates (except 3) was evaluated against a limited panel of leukemia cell lines (Molt 4, K562, U937, and Sup-T1). The major compounds 8 and 10 exhibited the most anti-proliferative potent effect, with IC50 values ranging from 1.2 to 7.1 μM. The Structure Activity Relationship (SAR) of the isolates suggested that the presence of lactone moieties is crucial for the anti-proliferative activity against leukemia cells. Our work indicated that the development of an efficient aquaculture protocols for soft corals led to the discovery of new secondary metabolites with unique structural features. Such protocols can lead to a sustainable supply of biologically active compounds in enough quantities for the pharmaceutical industry.

13-Acetoxysarcocrassolide Exhibits Cytotoxic Activity against Oral Cancer Cells through the Interruption of the Keap1/Nrf2/p62/SQSTM1 Pathway: The Need to Move Beyond Classical Concepts

“…13-AC exhibited a cytotoxic effect on bladder and stomach cancer cell lines by inducing apoptosis through the regulation of hnRNPs F/H and PPT1 as well as the activation p38/JNK pathway and the inhibition of PI3K/Akt growth pathways [17]. Our previous studies showed that 13-AC is an interesting compound from different perspectives including its unique chemical structure with specific functionality of α-methylene-γ-lactone, the potent cytotoxic effect against several cancer cell lines, and the high yield isolated from the cultured coral, Lobophytum crassum [16]. These compelling features encouraged us to work on this unique cytotoxic marine compound.…”

“…13-AC was separated from the coral Lobophytum crissum. The spectroscopic data (1D and 2D NMR) of the isolated compound were compared to those reported in the literature, and the chemical structure of 13-AC was confirmed [16]. A stock solution of 13-AC was prepared by dissolving the compound in DMSO (dimethyl sulfoxide) (20 µg/mL) and a series of dilutions was prepared before use.…”

“…The mice were fed with a laboratory diet and water. The specimens of the aquaculture Lobophytum crassum soft coral were collected in 2015 as reported in our previous study [16]. At the National Museum of Marine Biology & Aquarium (Pingtung, Taiwan), the coral was preserved and aquacultured.…”

Sinularin Selectively Kills Breast Cancer Cells Showing G2/M Arrest, Apoptosis, and Oxidative DNA Damage

“…Effective drug development relies on identifying more and better bioactive compounds, such as lead molecules for subsequent modeling and synthesis, with selective killing effects against breast cancer cells. Some natural marine products have been found to inhibit proliferation [ 8 , 9 ] and induce apoptosis by modulating ROS generation [ 10 , 11 , 12 ]. Marine organisms, such as soft corals, have been found to provide highly diverse and abundant bioactive compounds against several cancer types.…”

Culture systems influence the physiological performance of the soft coral Sarcophyton glaucum

“…The culture of alcyonacean soft corals (Cnidaria: Anthozoa: Octocorallia: Alcyonacea)- notably Sarcophyton , Sinularia , and Lobophyton - has advanced rapidly in recent decades given the needs to (1) explore the impacts of environmental change on their physiological performance and (2) develop a sustainable supply for both the marine cosmeceutical and aquarium trade industries 1 , 7 , 8 . Many cultured soft corals used in natural product research rely on natural seawater flow-through systems (FTS) 9 , 10 ; however, natural product yields may differ from those of wild populations 11 . Other studies have used recirculating aquaculture systems (RAS) in which seawater quality parameters can be readily and automatically modulated by a variety of microprocessor-based dosing systems 12 − 14 .…”