A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling

Natesh, Nagabhishek Sirpu; Arumugam, Madan Kumar; Sambhavi, B; Balakrishnan, Anandan; Katakia, Yash T.; Chatterjee, Suvro; Nagasundaram, Nagarajan

doi:10.1039/c9ra05262c

Cited by 8 publications

(4 citation statements)

References 78 publications

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“…Nagabhishek et al [47] demonstrated the antiangiogenic ability of Monacolin X in vivo, ex vivo, in vitro, and in silico models via downregulation of the VEGFR-2. The compound showed inhibition of in vivo angiogenesis in CAM assay and vascular sprouting in the aortic ring and also showed a reduction of ISVs and SIVs length in transgenic zebrafish embryos Tg (Kdr:EGFP).…”

Section: Monacolin Xmentioning

confidence: 99%

Efficacy of marine biomolecules on angiogenesis by targeting hypoxia inducible factor/vascular endothelial growth factor signaling in zebrafish model

Nathan

Ramachandran

2021

J Biochem & Molecular Tox

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Marine resources are notably explored for their unique biomolecules that have been designed to be drug targets for their immense potential against various pathologies. These biomolecules are mostly secondary metabolites from different species that include sponges, tunicates, echinoderms, ascidians, algae, and marine symbionts.Among the various biological activities of the marine biomolecules, antiangiogenic property has gained much significance in alternate therapy for treatment against cancer. Hypoxia inducible factor (HIF) and vascular endothelial growth factor (VEGF) are the prime signaling pathways related to angiogenesis that are exclusively designated as markers for critical selection of novel inhibitors. This is mainly due to their importance in tumor induction and regulatory control over other interlinked pathways involved in cancer. Small molecular drug screening using the zebrafish model has been an advantage in cancer research in recent times. This review addresses the importance of marine biomolecules and their antiangiogenic efficacy by targeting HIF/VEGF pathways experimented in the zebrafish model in the last decade. Thus, it would provide more clear insights into the role of biomolecules in alternative cancer therapy.

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Section: Monacolin Xmentioning

confidence: 99%

Efficacy of marine biomolecules on angiogenesis by targeting hypoxia inducible factor/vascular endothelial growth factor signaling in zebrafish model

Nathan

Ramachandran

2021

J Biochem & Molecular Tox

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“…Graded alcohol was used to dehydrate the slides, followed by xylene (2X, 5 min). After drying, the slides were mounted in toluene and imaged [ 81 , 82 ]. The following antibodies from various vendors were used for the immunohistochemistry study: anti-Ki 67 (Abcam, ab15580); Anti-SOD1 (CST 65778, Boston, MA, USA); Anti-GPX4 (ab125066, Abcam, Boston, MA, USA); Anti-4-Hydroxynonenal (R&D Systems; Biotechne, MAB3249, Minneapolis, MN, USA); Anti-MUC2 (Abcam, ab272692, Boston, MA, USA); Anti-MUC4 (Santa Cruz, SC-33654, Dallas, TX, USA); anti-claudin 1 (Proteintech, 13050-1-AP, Rosemont, IL, USA); anti-occludin (Proteintech, 66378-1-Ig); Anti-F4/80 (Abcam, ab300421, Boston, MA, USA); anti-pIKKβ (CST, 36214SF, Boston, MA, USA); anti-pNF-kB (Abcam, ab131100, Boston, MA, USA); anti-TNF-α (Abcam, ab1793, Boston, MA, USA); Anti-pSTAT3 (CST, 9145, Boston, MA, USA); Anti-CD3 (CST, 78588, Boston, MA, USA); Anti-RORγ (Abcam, ab207082, Boston, MA, USA); Anti-FOXp3 (CST, 12653, Boston, MA, USA); Anti-MPO (Proteintech, 22225-1-AP); Anti-Ppar g (Proteintech, 16643-1-AP, Rosemont, IL, USA).…”

Section: Methodsmentioning

confidence: 99%

Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis and Ameliorates Colitis

Jean Wilson,

Sirpu Natesh,

Ghadermazi

et al. 2023

IJMS

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Gut microbiota plays a crucial role in inflammatory bowel diseases (IBD) and can potentially prevent IBD through microbial-derived metabolites, making it a promising therapeutic avenue. Recent evidence suggests that despite an unclear underlying mechanism, red cabbage juice (RCJ) alleviates Dextran Sodium Sulfate (DSS)-induced colitis in mice. Thus, the study aims to unravel the molecular mechanism by which RCJ modulates the gut microbiota to alleviate DSS-induced colitis in mice. Using C57BL/6J mice, we evaluated RCJ’s protective role in DSS-induced colitis through two cycles of 3% DSS. Mice were daily gavaged with PBS or RCJ until the endpoint, and gut microbiota composition was analyzed via shotgun metagenomics. RCJ treatment significantly improved body weight (p ≤ 0.001), survival in mice (p < 0.001) and reduced disease activity index (DAI) scores. Further, RCJ improved colonic barrier integrity by enhancing the expression of protective colonic mucins (p < 0.001) and tight junction proteins (p ≤ 0.01) in RCJ + DSS-treated mice compared to the DSS group. Shotgun metagenomic analysis revealed an enrichment of short-chain fatty acids (SCFAs)-producing bacteria (p < 0.05), leading to increased Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) activation (p ≤ 0.001). This, in turn, resulted in repression of the nuclear factor κB (NFκB) signaling pathway, causing decreased production of inflammatory cytokines and chemokines. Our study demonstrates colitis remission in a DSS-induced mouse model, showcasing RCJ as a potential modulator for gut microbiota and metabolites, with promising implications for IBD prevention and treatment.

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“…KMM 701 targeting two alkaloid binding sites on the molecule [173]; marine sponge Clathria frondifera associated fungus Monascus sp. NMK7-derived polyketide monacolin X (147) that suppressed angiogenesis by downregulation of the VEGFR2 signaling pathway [174]; marine sponge Diacarnus erythraeanus-derived norterpene peroxide (-)-muqubilin A (148) found to be a retinoic acid receptor α positive allosteric modulator and retinoic acid signaling enhancer [175]; marine sponge Mycale aff. nullarosette-derived polyketide mycalolide A (149) that inhibited cytokinesis by disruption of F-actin and binucleation induction [176]; marine blue mussel Mytilus edulis-derived dodecapeptide (150) that promoted growth of osteoblasts, bone loss reduction in ovariectomized mice and interacted with integrins 1L5G and 3V14 [177]; tilapia Oreochromis niloticus-derived oligopeptide (151) shown to be protective of angiotensin II-induced hypertensive endothelial injury by affecting Nrf2 and NF-kB signaling pathways [178]; marine fungus Penicillium sp.…”

Section: Marine Compounds With Miscellaneous Mechanisms Of Actionmentioning

confidence: 99%

Marine Pharmacology in 2019‐2021: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti‐Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

Mayer,

Swanson-Mungerson

et al. 2024

Preprint

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The current 2019-2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. Preclinical marine pharmacology research during 2019-2021 was published by researchers in 42 countries and contributed novel mechanism of action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural products pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis,and antiviral mechanism of action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes. Thus, in 2019-2021, a very active preclinical marine natural product pharmacology pipeline provided novel mechanism of actions as well as new lead chemistry for the clinical marine pharmaceutical pipeline targeting the therapy of several disease categories.

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A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling

Abstract: Cancer is one of the leading causes of global deaths and there is an urgent need for the development cancer treatment; targeting VEGFR2 could be one of the promising therapies.

Cited by 8 publications

References 78 publications

Efficacy of marine biomolecules on angiogenesis by targeting hypoxia inducible factor/vascular endothelial growth factor signaling in zebrafish model

Efficacy of marine biomolecules on angiogenesis by targeting hypoxia inducible factor/vascular endothelial growth factor signaling in zebrafish model

Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis and Ameliorates Colitis

Marine Pharmacology in 2019‐2021: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti‐Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

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