INSERM, U1029, Université de Bordeaux, Bordeaux, France.
Curr Med Chem. 2013;20(4):583-91. doi: 10.2174/0929867311320040010.
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.
The objective of this study is to examine and compare anti-tumorigenic activity of furin inhibitory flavonoid compounds from OI.
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.
药用植物 Oroxylum indicum（OI）因其多种观察到的生物活性而引起了相当多的研究兴趣。特别引人关注的是其抗肿瘤活性。该植物是黄酮类化合物及其糖苷的丰富来源。最近，黄酮类化合物被描述为超家族 Proprotein Convertase Subtilisin/Kexins（PCSKs）的 kexin 型蛋白酶抑制剂，这些蛋白酶与肿瘤生长和恶性有关。这些酶，特别是 furin（PCSK3），将无活性的前体生长因子切割成成熟形式，促进肿瘤生长。因此，寻找 furin 抑制剂成为癌症研究的热点。在这方面，具有已知抗癌活性的植物 OI 可能提供一个重要的来源。
本研究的目的是研究和比较 OI 中具有抗肿瘤活性的 furin 抑制性黄酮化合物。
进行了研究以评估从 OI 中分离出的 4 种黄酮类化合物黄芩素、白杨素、氧马钱素及其糖苷对 CT-26 细胞增殖和迁移的影响。数据显示，黄芩素对分析的肿瘤细胞系的增殖和迁移表现出最强烈的抑制作用。黄芩素在 10 μM 时甚至在 5 天后完全阻断了增殖。这些结果与体外抗 furin 活性一致，该活性是通过测定荧光肽和原 hVEGF-C 作为底物来测量的。成熟的 VEGF-C 是肿瘤进展的强烈指标和生物标志物，因此抗 furin 活性可以解释黄芩素观察到的抗癌特性。由于黄芩素是 OI 的主要成分，我们的数据为 OI 观察到的抗癌活性提供了科学依据，也为未来作为潜在抗肿瘤药物的探索提供了一个新的先导分子。
