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

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 characteri...

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Autores principales: Nagabhishek, Sirpu Natesh, Madan Kumar, Arumugam, B., Sambhavi, Balakrishnan, Anandan, Katakia, Yash T., Chatterjee, Suvro, Nagasundaram, Nagarajan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070443/
https://www.ncbi.nlm.nih.gov/pubmed/35528587
http://dx.doi.org/10.1039/c9ra05262c
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author Nagabhishek, Sirpu Natesh
Madan Kumar, Arumugam
B., Sambhavi
Balakrishnan, Anandan
Katakia, Yash T.
Chatterjee, Suvro
Nagasundaram, Nagarajan
author_facet Nagabhishek, Sirpu Natesh
Madan Kumar, Arumugam
B., Sambhavi
Balakrishnan, Anandan
Katakia, Yash T.
Chatterjee, Suvro
Nagasundaram, Nagarajan
author_sort Nagabhishek, Sirpu Natesh
collection PubMed
description 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.
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spelling pubmed-90704432022-05-05 A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling Nagabhishek, Sirpu Natesh Madan Kumar, Arumugam B., Sambhavi Balakrishnan, Anandan Katakia, Yash T. Chatterjee, Suvro Nagasundaram, Nagarajan RSC Adv Chemistry 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. The Royal Society of Chemistry 2019-08-27 /pmc/articles/PMC9070443/ /pubmed/35528587 http://dx.doi.org/10.1039/c9ra05262c Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Nagabhishek, Sirpu Natesh
Madan Kumar, Arumugam
B., Sambhavi
Balakrishnan, Anandan
Katakia, Yash T.
Chatterjee, Suvro
Nagasundaram, Nagarajan
A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling
title A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling
title_full A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling
title_fullStr A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling
title_full_unstemmed A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling
title_short A marine sponge associated fungal metabolite monacolin X suppresses angiogenesis by down regulating VEGFR2 signaling
title_sort marine sponge associated fungal metabolite monacolin x suppresses angiogenesis by down regulating vegfr2 signaling
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070443/
https://www.ncbi.nlm.nih.gov/pubmed/35528587
http://dx.doi.org/10.1039/c9ra05262c
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