A cytotoxic triterpenoid from a Periplaneta americana-derived, Gordonia hongkongensis WA12-1-1.

The secondary metabolites produced by microorganisms are a source of novel compounds with antitumor activities. In this study, we isolated biologically active secondary metabolites produced by microorganisms in the intestinal tract of Periplaneta americana. Based on the 16S rRNA gene sequencing, Gordonia hongkongensis WA12-1-1 was identified as the main microorganisms in the intestinal tract of P. americana. The obtained sequence was deposited in the National Center for Biotechnology Information (NCBI) database under the accession number MZ348554. The isolated secondary metabolites were separated and purified by thin layer chromatography, silica gel column chromatography, Sephadex column chromatography, open octadecyl silane column chromatography, high-performance liquid chromatography (HPLC), and semipreparative HPLC. Next, the structure of individual compounds was determined by ultraviolet spectroscopy, nuclear magnetic resonance, and mass spectrometry. A total of 20 compounds were isolated from the secondary metabolites produced by G. hongkongensis WA12-1-1. A total of 12 compounds were obtained from the crude ethyl acetate extract of the culture supernatant and eight from the cellular fraction. Compound 1 was identified as a triterpenoid named gordonterpene and showed cytotoxicity against A549 and HepG2 cell lines. These findings form a basis for further studies on the bioactivity of gordonterpene to tumor cells.

Anti-Tumor Secondary Metabolites Originating from Fungi in the South China Sea's Mangrove Ecosystem.

A mangrove is a unique ecosystem with abundant resources, in which fungi are an indispensable microbial part. Numerous mangrove fungi-derived secondary metabolites are considerable sources of novel bioactive substances, such as polyketides, terpenoids, alkaloids, peptides, etc., which arouse people's interest in the search for potential natural anti-tumor drugs. This review includes a total of 44 research publications that described 110 secondary metabolites that were all shown to be anti-tumor from 39 mangrove fungal strains belonging to 18 genera that were acquired from the South China Sea between 2016 and 2022. To identify more potential medications for clinical tumor therapy, their sources, unique structures, and cytotoxicity qualities were compiled. This review could serve as a crucial resource for the research status of mangrove fungal-derived natural products deserving of further development.

Prodigiosin from Serratia Marcescens in Cockroach Inhibits the Proliferation of Hepatocellular Carcinoma Cells through Endoplasmic Reticulum Stress-Induced Apoptosis.

Hepatocellular carcinoma (HCC) is the most common primary liver malignant tumor, and the targeted therapy for HCC is very limited. Our previous study demonstrated that prodigiosin(PG), a secondary metabolite from Serratia marcescens found in the intestinal flora of cockroaches, inhibits the proliferation of HCC and increases the expression of CHOP, a marker protein for endoplasmic reticulum stress (ERS)-mediated apoptosis, in a dose-dependent manner. However, the mechanisms underlying the activity of PG in vivo and in vitro are unclear. This study explored the molecular mechanisms of PG-induced ERS against liver cancer in vitro and in vivo. The apoptosis of hepatocellular carcinoma cells induced by PG through endoplasmic reticulum stress was observed by flow cytometry, colony formation assay, cell viability assay, immunoblot analysis, and TUNEL assay. The localization of PG in cells was observed using laser confocal fluorescence microscopy. Flow cytometry was used to detect the intracellular Ca2+ concentration after PG treatment. We found that PG could promote apoptosis and inhibit the proliferation of HCC. It was localized in the endoplasmic reticulum of HepG2 cells, where it induces the release of Ca2+. PG also upregulated the expression of key unfolded response proteins, including PERK, IRE1α, Bip, and CHOP, and related apoptotic proteins, including caspase3, caspase9, and Bax, but down-regulated the expression of anti-apoptotic protein Bcl-2 in liver cancer. Alleviating ERS reversed the above phenomenon. PG had no obvious negative effects on the functioning of the liver, kidney, and other main organs in nude mice, but the growth of liver cancer cells was inhibited by inducing ERS in vivo. The findings of this study showed that PG promotes apoptosis of HCC by inducing ERS.

Murrangatin suppresses angiogenesis induced by tumor cell-derived media and inhibits AKT activation in zebrafish and endothelial cells.

INTRODUCTION: Lung cancer is a major cancer type and a leading cause of cancer-related death. Angiogenesis plays a crucial role in lung cancer pathogenesis and its inhibition is beneficial to patients. MATERIALS AND METHODS: Murrangatin, a natural product, can inhibit the proliferation of lung cancer cells, so herein we investigated its anti-angiogenic effects in transgenic zebrafish TG (fli1: EGFP) and in lung cancer cell-induced angiogenesis in human umbilical vein endothelial cells. RESULTS: We found that murrangatin strongly inhibited the growth of subintestinal vessels in zebrafish embryos and tumor conditioned media-induced angiogenic phenotypes including cell proliferation, cell invasion, cell migration, and tube formation. Additionally, murrangatin greatly attenuated conditioned medium-induced AKT phosphorylation, but not extracellular signal-regulated kinase 1/2 phosphorylation. DISCUSSION AND CONCLUSION: These findings indicate that murrangatin can inhibit tumor-induced angiogensis, at least in part through the regulation of AKT signaling pathways. Murrangatin may, therefore, be a potential candidate for the development of new anti-lung-cancer drugs.

Micrometam C Protects against Oxidative Stress in Inflammation Models in Zebrafish and RAW264.7 Macrophages.

Micrometam C is a core of novel marine compound isolated from the mangrove associates Micromelum falcatum. In this study, we investigated the protective effects of micrometam C in inflammation models in the transgenic zebrafish line Tg (corola: eGFP) and RAW264.7 macrophages. We found that micrometam C significantly suppressed the migration of immune cells in tail-cutting-induced inflammation in transgenic zebrafish and reduced lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) in both zebrafish and macrophages. In addition, micrometam C also restored LPS-induced reduction of endogenous antioxidants, such as catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD). The protective effects of micrometam C were in parallel to its inhibition of NADPH oxidase and nuclear factor-kappa-binding (NF-κB) activity. Thus, the present results demonstrate that micrometam C protects against LPS-induced inflammation possibly through its antioxidant property.

Marine compound catunaregin inhibits angiogenesis through the modulation of phosphorylation of akt and eNOS in vivo and in vitro.

Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.

Two new coumarins from Micromelum falcatum with cytotoxicity and brine shrimp larvae toxicity.

Two new coumarins, 7-methoxy-8-(2-hydroxmethyl-1-O-isovaleryl-4-butenyl)-coumarin (1) and 7-methoxy-8-(1-hydroxy-2-O-ß-glucopyranosyl-3-methyl-4-butene-1-yl)coumarin (2), and twelve known coumarins 3-14 were isolated from the stem bark of Micromelum falcatum. The structures of compounds 1-14 were elucidated by extensive spectroscopic data analyses. The toxicity of compounds 1-14 was tested using a brine shrimp assay and in vitro antiproliferative assay against mammary cancer (F10) and lung cancer (HvEvc) cell lines by the MTT method. Some compounds had moderate activities. All compounds were also tested against the microorganisms Bacillus subtilis, Bacillus thuringiensis and Escherichia coli, but no activity was observed.