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Issue 46, 2019, Issue in Progress
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A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling

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Abstract

Cancer is one of the leading causes of global death and there is an urgent need for the development of cancer treatment; targeting VEGFR2 could be one of the promising therapies. In the present study, previously isolated marine fungal metabolite monacolin X, suppresses in vitro angiogenic characteristics such as proliferation, migration, adhesion, invasion and tube formation of HUVECs when stimulated by VEGF, at a non-toxic concentration. Monacolin X downregulated VEGFR2, PKCα and PKCη mRNA expression. Further, monacolin X inhibited in vivo angiogenesis in CAM assay, vascular sprouting in aortic ring, decreased ISV and SIV length and diameter in Tg (Kdr:EGFP)/ko1 zebrafish embryos. Monacolin X showed reduced protein expression of pVEGFR2, pAKT1, pMAPKAPK2, pFAK and pERK1 in breast cancer lines and in DMBA induced mammary carcinoma in SD rats showed tumor regression and anti-angiogenesis ability via decrease pVEGFR2 and pAKT1 protein expression. In silico studies also revealed monacolin X ability to bind to crucial amino acid Cys 919 in the active site of VEGFR2 suggesting it to be a potent VEGFR2 inhibitor.

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

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Publication details

The article was received on 10 Jul 2019, accepted on 08 Aug 2019 and first published on 27 Aug 2019


Article type: Paper
DOI: 10.1039/C9RA05262C
RSC Adv., 2019,9, 26646-26667
  • Open access: Creative Commons BY license
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    A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling

    S. N. Nagabhishek, A. Madan Kumar, S. B., A. Balakrishnan, Y. T. Katakia, S. Chatterjee and N. Nagasundaram, RSC Adv., 2019, 9, 26646
    DOI: 10.1039/C9RA05262C

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