Safranal Inhibits Angiogenesis via Targeting HIF-1α/VEGF Machinery: In Vitro and Ex Vivo Insights

Nature has a nearly infinite inventory of unexplored phytochemicals and biomolecules that have the potential to treat a variety of diseases. Safranal exhibits anti-cancer property and the present study explores its antiangiogenic property. Hepatocellular carcinoma (HCC) ranks as the sixth deadliest...

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Main Authors: Ali Abdalla, Chandraprabha Murali, Amr Amin
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.789172/full
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author Ali Abdalla
Chandraprabha Murali
Amr Amin
Amr Amin
author_facet Ali Abdalla
Chandraprabha Murali
Amr Amin
Amr Amin
author_sort Ali Abdalla
collection DOAJ
description Nature has a nearly infinite inventory of unexplored phytochemicals and biomolecules that have the potential to treat a variety of diseases. Safranal exhibits anti-cancer property and the present study explores its antiangiogenic property. Hepatocellular carcinoma (HCC) ranks as the sixth deadliest among all cancer types. Targeting the non-tumor vasculature supporting system is very promising as it has less plasticity, unlike malignant cells that are often associated with issues like drug resistance, poor prognosis, and relapse. In this study, we successfully inhibited the proliferation of primary human umbilical vein endothelial cells (HUVEC) with an IC50 of 300μM and blocked VEGF secretion in HepG2 cells. Furthermore, safranal inhibited VEGF-induced angiogenesis in vitro and ex vivo via scratch wound assay, tube formation assay, transmembrane assay, and aortic ring assay. In addition, safranal downregulated the in vitro expression of HIF-1α, VEGF, VEGFR2, p-AKT, p-ERK1/2, MMP9, p-FAK, and p-STAT3. The present study is the first to reveal the antiangiogenic potential of safranal and propose its possible underlying mechanism in HCC.
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spelling doaj.art-0dfb45d49f634e1e92fa3eccf0d509902022-12-22T04:05:23ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-02-011110.3389/fonc.2021.789172789172Safranal Inhibits Angiogenesis via Targeting HIF-1α/VEGF Machinery: In Vitro and Ex Vivo InsightsAli Abdalla0Chandraprabha Murali1Amr Amin2Amr Amin3 Weinberg Institute for Cognitive Science, University of Michigan, Ann Arbor, MI, United StatesBiology Department, College of Science, United Arab Emirates University, Al-Ain, United Arab EmiratesBiology Department, College of Science, United Arab Emirates University, Al-Ain, United Arab EmiratesThe College, The University of Chicago, Chicago, IL, United StatesNature has a nearly infinite inventory of unexplored phytochemicals and biomolecules that have the potential to treat a variety of diseases. Safranal exhibits anti-cancer property and the present study explores its antiangiogenic property. Hepatocellular carcinoma (HCC) ranks as the sixth deadliest among all cancer types. Targeting the non-tumor vasculature supporting system is very promising as it has less plasticity, unlike malignant cells that are often associated with issues like drug resistance, poor prognosis, and relapse. In this study, we successfully inhibited the proliferation of primary human umbilical vein endothelial cells (HUVEC) with an IC50 of 300μM and blocked VEGF secretion in HepG2 cells. Furthermore, safranal inhibited VEGF-induced angiogenesis in vitro and ex vivo via scratch wound assay, tube formation assay, transmembrane assay, and aortic ring assay. In addition, safranal downregulated the in vitro expression of HIF-1α, VEGF, VEGFR2, p-AKT, p-ERK1/2, MMP9, p-FAK, and p-STAT3. The present study is the first to reveal the antiangiogenic potential of safranal and propose its possible underlying mechanism in HCC.https://www.frontiersin.org/articles/10.3389/fonc.2021.789172/fullsafranalVEGFHIF-1αangiogenesiscancer
spellingShingle Ali Abdalla
Chandraprabha Murali
Amr Amin
Amr Amin
Safranal Inhibits Angiogenesis via Targeting HIF-1α/VEGF Machinery: In Vitro and Ex Vivo Insights
Frontiers in Oncology
safranal
VEGF
HIF-1α
angiogenesis
cancer
title Safranal Inhibits Angiogenesis via Targeting HIF-1α/VEGF Machinery: In Vitro and Ex Vivo Insights
title_full Safranal Inhibits Angiogenesis via Targeting HIF-1α/VEGF Machinery: In Vitro and Ex Vivo Insights
title_fullStr Safranal Inhibits Angiogenesis via Targeting HIF-1α/VEGF Machinery: In Vitro and Ex Vivo Insights
title_full_unstemmed Safranal Inhibits Angiogenesis via Targeting HIF-1α/VEGF Machinery: In Vitro and Ex Vivo Insights
title_short Safranal Inhibits Angiogenesis via Targeting HIF-1α/VEGF Machinery: In Vitro and Ex Vivo Insights
title_sort safranal inhibits angiogenesis via targeting hif 1α vegf machinery in vitro and ex vivo insights
topic safranal
VEGF
HIF-1α
angiogenesis
cancer
url https://www.frontiersin.org/articles/10.3389/fonc.2021.789172/full
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AT amramin safranalinhibitsangiogenesisviatargetinghif1avegfmachineryinvitroandexvivoinsights
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