Marine Drugs

11 pages, 3264 KiB

Open AccessArticle

An Oncolytic Vaccinia Virus Expressing Aphrocallistes Vastus Lectin Modulates Hepatocellular Carcinoma Metabolism via ACSS2/TFEB-Mediated Autophagy and Lipid Accumulation

by Qiang Wang, Simeng Zhou, Yin Wang, Yajun Gao, Yanrong Zhou, Ting Ye, Gongchu Li and Kan Chen

Mar. Drugs 2025, 23(8), 297; https://doi.org/10.3390/md23080297 - 24 Jul 2025

Abstract

Hepatocellular carcinoma (HCC) remains a therapeutic challenge due to metabolic plasticity and drug resistance. Oncolytic viruses (OVs), such as thymidine kinase-deleted vaccinia virus (oncoVV), selectively lyse tumors while stimulating antitumor immunity, however, their metabolic interplay with cancer cells is poorly understood. Here, we engineered an oncoVV-expressing Aphrocallistes vastus lectin (oncoVV-AVL) and uncovered its unique ability to exploit the ACSS2/TFEB axis, driving metabolic competition in HCC. In vitro, oncoVV-AVL triggered cell autophagy and lipid accumulation (3.4–5.7-fold upregulation of FASN and ACC1) while suppressing glucose uptake (41–63% higher extracellular glucose and 33–34% reduced lactate). Mechanistically, oncoVV-AVL upregulated acetyl-CoA synthetase 2 (ACSS2), promoting its nuclear translocation and interaction with transcription factor EB (TFEB) to concurrently activate lipogenesis and autophagic flux. The pharmacological inhibition of ACSS2 abolished these effects, confirming its central role. In vivo, oncoVV-AVL suppressed tumor growth while inducing lipid deposition (2-fold triglyceride increase), systemic hypoglycemia (42% glucose reduction), and autophagy activation (elevated LC3B-II/I ratios). This study establishes ACSS2 as a metabolic checkpoint in OV therapy, providing a rationale for combining oncolytic virotherapy with metabolic modulators in HCC. Full article

(This article belongs to the Special Issue Marine Glycobiology)

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26 pages, 1809 KiB

Open AccessReview

Salt-Adapted Microorganisms: A Promising Resource for Novel Anti-Cancer Drug Discovery

by Longteng Fang, Liping Xu, Marhaba Kader, Tingting Ding, Shiyang Lu, Dong Wang, Amit Raj Sharma and Zhiwei Zhang

Mar. Drugs 2025, 23(8), 296; https://doi.org/10.3390/md23080296 - 24 Jul 2025

Abstract

Microorganisms serve as a vital source of natural anticancer agents, with many of their secondary metabolites already employed in clinical oncology. In recent years, salt-adapted microbes, including halophilic and halotolerant species from marine, salt lake, and other high-salinity environments, have gained significant attention. Their unique adaptation mechanisms and diverse secondary metabolites offer promising potential for novel anticancer drug discovery. This review consolidated two decades of research alongside current global cancer statistics to evaluate the therapeutic potential of salt-adapted microorganisms. Halophilic and halotolerant species demonstrate significant promise, with their bioactive metabolites exhibiting potent inhibitory effects against major cancer cell lines, particularly in lung and breast cancer. Evidence reveals structurally unique secondary metabolites displaying enhanced cytotoxicity compared to conventional anticancer drugs. Collectively, salt-adapted microorganisms represent an underexplored yet high-value resource for novel anticancer agents, offering potential solutions to chemotherapy resistance and treatment-related toxicity. Full article

(This article belongs to the Special Issue Marine Bioactive Agents with Anticancer Potential: Discovery and Molecular Mechanisms)

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26 pages, 8725 KiB

Open AccessArticle

Novel 3D-Printed Replica Plate Device Ensures High-Throughput Antibacterial Screening of Halophilic Bacteria

by Kaloyan Berberov, Nikolina Atanasova, Nikolay Krumov, Boryana Yakimova, Irina Lazarkevich, Stephan Engibarov, Tsvetozara Damyanova, Ivanka Boyadzhieva and Lyudmila Kabaivanova

Mar. Drugs 2025, 23(8), 295; https://doi.org/10.3390/md23080295 - 23 Jul 2025

Abstract

Antibiotic resistance is one of the most significant public health issues today. As a consequence, there is an urgent need for novel classes of antibiotics. This necessitates the development of highly efficient screening methods for the rapid identification of antibiotic-producing bacteria. Here, we describe a new method for high-throughput screening of antimicrobial compounds (AMC) producing halophilic bacteria. Our methodology used a newly designed 3D-printed Petri plate replicator used for drop deposition and colony replication. We employed this device in combination with a modified agar overlay assay to screen more than 7400 bacterial colonies. A total of 54 potential AMC producers were discovered at a success rate of 0.7%. Although 40% of them lost their antibacterial activity during the secondary screening, 22 strains retained inhibitory activity and were able to suppress the growth of one or more safe relatives of the ESKAPE group pathogens. The ethyl acetate extract from the most potent strain, Virgibacillus salarius POTR191, demonstrated moderate antibacterial activity against Enterococcus faecalis, Acinetobacter baumanii, and Staphylococcus epidermidis with minimal inhibitory concentrations of 128 μg/mL, 128 μg/mL, and 512 μg/mL, respectively. We propose that our replica plate assay could be used for target-based antimicrobial screening of various extremophilic bacteria. Full article

(This article belongs to the Special Issue Genome Mining and Drug Discovery of Marine and Halophilic Microorganisms)

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17 pages, 13984 KiB

Open AccessArticle

Isolation and Purification of Novel Antioxidant Peptides from Mussel (Mytilus edulis) Prepared by Marine Bacillus velezensis Z-1 Protease

by Jing Lu, Pujing Shi, Yutian Cao, Bingxin Shi, Huilin Shen, Shuai Zhao, Yuchen Gao, Huibing Chi, Lei Wang and Yawei Shi

Mar. Drugs 2025, 23(8), 294; https://doi.org/10.3390/md23080294 - 23 Jul 2025

Abstract

Mussels are nutrient-rich but perishable, resulting in substantial resource loss. A protease-producing strain (Bacillus velezensis Z-1, Mytilus edulis) isolated from marine sludge was used to hydrolyze mussels, producing Y-1, a hydrolysate with antioxidant activity. In this study, ultrafiltration, gel chromatography, and LC-MS/MS were employed to isolate and identify bioactive peptides from the hydrolysate. The results revealed that the hydrolysate exhibited antioxidant activity, pancreatic cholesterol esterase inhibitory activity, pancreatic lipase inhibitory activity, and α-glucosidase inhibitory activity. Molecular docking using AutoDock Tools 1.5.6 was performed to analyze the interactions of peptides with CD38 and Keap1, leading to the identification of five potentially bioactive peptides: VPPFY, IMLFP, LPFLF, FLPF, and FPRIM. These peptides formed hydrogen bonds and hydrophobic interactions with CD38 and Keap1, demonstrating strong DPPH radical scavenging and superoxide anion radical scavenging capacities. This study highlights the multifunctional bioactive potential of these peptides, offering insights into their therapeutic applications. The findings provide a novel approach for the effective utilization of mussel resources and highlight their potential application value in the development of functional foods. Full article

(This article belongs to the Section Marine Pharmacology)

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Mar. Drugs, Volume 23, Issue 8 (August 2025) – 4 articles

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