Title:Inhibition of Tumor Cells Proliferation and Migration by the Flavonoid Furin Inhibitor Isolated From Oroxylum indicum
Volume: 20
Issue: 4
Author(s): C. Lalou, A. Basak, P. Mishra, B.C. Mohanta, R. Banik, B. Dinda and A.M. Khatib
Affiliation:
Keywords:
Proprotein convertase subtilisin kexin, furin, proteolytic enzymes, proprotein processing, protease inhibitors, natural flavonoids, furin inhibitors, nonpeptide inhibitors, anticancer activity, Oroxylum indicum (OI)
Abstract: Background: The medicinally active plant Oroxylum indicum (OI) has drawn considerable research interest because of its
many observed biological activities. Of particular interest is its antitumorigenic activity. The plant is a rich source of flavonoids and their
glycosides. Recently flavonoids have been described as inhibitors of kexin-type proteases of superfamily Proprotein Convertase Subtilisin/
Kexins (PCSKs) which have been implicated in tumor growth and malignancy. These enzymes particularly furin (PCSK3) cleaves
inactive precursor growth factors into their mature forms that promote tumor growth. As a result, finding furin-inhibitors became of high
interest in cancer research. In this regard, the plant OI with known anticancer activities may provide an important source. Objective: The
objective of this study is to examine and compare anti-tumorigenic activity of furin inhibitory flavonoid compounds from OI. Results:
Studies were conducted to evaluate the effect on CT-26 cell proliferation and migration of 4 flavonoids baicalein, chrysin, oroxylin-A
and its glycoside isolated from OI. Data revealed that baicalein exhibited most potent inhibitory effect on proliferation and migration on
the analyzed tumor cell line. Baicalein at 10 μM completely blocked the proliferation even after 5 days. The results are consistent with
the observed in vitro anti-furin activity of baicalein as measured against a fluorogenic peptide and pro-hVEGF-C as substrates. Mature
VEGF-C is a strong indicator and biomarker of tumor progression and therefore the antifurin activity may explain the observed anticancer
properties of baicalein. Since baicalein is the major constituent of OI, our data provided scientific rationale for the observed anticancer
activity of OI and also offered a new lead molecule for future exploration as potential antitumor agents.