Abstract
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.
Highlights
Liver cancer is one of the most fatal cancers [1]
Based on our earlier study on the Hepatocellular carcinoma (HCC) cells [17], and in order to further assess its antiangiogenic potential, we examined the inhibitory effect of safranal on cell viability in HUVEC cells
Safranal inhibited the growth of human endothelial cells, HUVEC, at the two tested doses with, and without, vascular endothelial growth factor (VEGF) induction suggesting an antiproliferative capacity that may be mediated through VEGF and its receptors
Summary
Liver cancer is one of the most fatal cancers [1]. Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, ranks sixth deadliest among all cancer types [2]. Many forms of cancer, including HCC, cause the deregulation of multiple signaling pathways that manage cell proliferation, metastasis, and angiogenesis [4]. Angiogenesis is a tightly regulated physiological process. It is essential in wound healing, embryogenesis, and other vital processes in growth and development [9]. Epidermal growth factor (EGF), insulin-like growth factor (IGF), and vascular endothelial growth factor (VEGF) are the most frequently studied signaling molecules in angiogenesis. Overexpression of these growth factors, VEGF and its receptors, has been widely reported in HCC patients [10]
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