6-Bromohypaphorine isolated from red sea cucumbers Apostichopus japonicus exhibits potent anticancer activity in A549 cancer cell line
Introduction
The bioactive metabolites of marine invertebrates are bio-resources with a diverse range of chemical structures [1,2]. In marine organisms, the secondary metabolites can act as a defensive mechanism to protect against invaders. Metabolites have great potential as anticancer agents [3]. Sea cucumbers (Apostichopus japonicus) have been used worldwidely in traditional tonics for thousands of years, especially in Northeast Asian countries, such as Korea, China, and Japan [4]. There are different A. japonicus with different colors, such as red, blue, and black [5,6]. Commercially, the origin of A. japonicus is important to consumers because color differentiation is the key factor that determines its taste and price [7]. Peptides, polysaccharides, and other nutrients from sea cucumbers exhibit a wide range of pharmacological characteristics, including anticancer, antimicrobial, antifungal, and anti-inflammatory properties [8,9]. Therefore, isolation and characterization of bioactive compounds from A. japonicas are of theoretical and practical significance.
Over the past few decades, there has been an increasing research interest in exploring marine bio-compounds. L-6-Bromohypaphorine (6-BHP) was isolated from the sponge for the first time, Pachymatisma johnstoni [10]. It was also found in the tunicates (Didemnum candidum and Hermissenda crassicornis) [11]. A previous report showed that 6-BHP was an agonist of the human α7 nicotinic acetylcholine receptor [12]. Another study indicated that 6-BHP isolated from the sub-Arctic sponge Geodia barrette had anti-inflammatory effects on human dendritic cells [13]. However, anticancer properties of 6-BHP have not yet been reported. In this study, we first isolated 6-BHP from sea cucumbers A. japonicus, and evaluated its anticancer properties.
Section snippets
Instruments and reagents
Reversed-phase high-performance liquid chromatography (HPLC) analysis was carried out on an Agilent 1220 Infinity II LC System. Nuclear magnetic resonance spectroscopy (NMR) measurement was carried out on a Bruker AV600 NMR spectrometer (Bruker Co., Karlsruhe, Germany). Agilent 6520 Quadrupole-time-of-flight mass spectrometer (Agilent Technologies, USA) was used to acquire mass spectra. Human breast cancer cell line MCF-7, human liver cancer cell line Hep3B, Mus musculus skin melanoma cell line
Isolation and identification 6-BHP from A. japonicus
6-BHP was isolated from A. japonicus by partition using ethanol, hexane, chloroform, ethyl acetate, and n-butanol. The n-butanol fraction was separated by PTLC; 6-BHP was isolated by HPLC (Fig. 2). The structure of 6-BHP was identified by comparing the NMR data (Table 1) with previous report [10]. The ESI-MS data showed the following results: [2M+H]+ ion (C28H35O4N479Br2, m/z 649.1020) and m/z [M+Na]+ ion (C14H17O2N279BrNa, 347.0366) were detected in the positive ion mode. The theoretical m/z
Conclusions
In this study, we showed the antiproliferative effects of 6-BHP, which was isolated from red sea cucumbers (A. japonicus) for the first time. Furthermore, it was found that 6-BHP regulated apoptotic regulators via mitochondria-mediated apoptosis pathway. This research expanded our understanding of the biological properties of sea cucumbers and the bioactive compounds they contained. This study yielded promising results and laied a foundation for further research into additional anticancer
Declaration of interests
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgement
This research was funded by Scientific and Technological Development Program of Jilin province of China, grant number 20200201619JC, 20191102065YY, 20200201141JC, 20200404041YY.
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