植物化合物，被称为植物化学物质，一直作为开发新型抗癌药物和治疗恶性肿瘤的宝贵资源。在这些植物化学物质中，黄芩素是一种新兴的抗肿瘤黄酮类化合物，来源于黄芩（黄芩科），但其作用机制和分子靶点尚未完全阐明。本研究发现了黄芩素抗肿瘤活性的新机制，证明了透明质酸介导的运动受体（HMMR）和雄激素受体（AR）是黄芩素在人类肿瘤细胞中的新分子靶点。我们观察到HMMR与广泛的人类癌症的不良预后密切相关，并发现，黄芩素显著降低了HMMR的mRNA和蛋白质水平。进一步的记者试验揭示，黄芩素通过Egr-1、E2F3α和血清反应因子（SRF）的转录调节机制抑制了HMMR。我们还发现，黄芩素显著抑制了激素敏感型前列腺癌细胞的雄激素反应，这可能是由于黄芩素降低了AR启动子活性。此外，黄芩素明显诱导肿瘤抑制性miR-30C的表达，该miRNA可能部分参与黄芩素介导的自噬和抗癌效应。总的来说，我们的研究揭示了黄芩素表现出的抗癌效应的新的多样化机制，暗示黄芩素可能成为针对人类肿瘤的潜在治疗药物，并作为HMMR和AR的抑制剂。© 2023. The Pharmaceutical Society of Korea.

Natural compounds known as phytochemicals have served as valuable resources for the development of new anti-cancer drugs and treatment of malignancies. Among these phytochemicals, baicalein is an emerging anti-tumor flavonoid obtained from Scutellaria baicaleinsis (Lamiaceae), but its underlying mechanisms of action and molecular targets have not yet been completely elucidated. Here, we identified new mechanisms for the anti-tumor activities of baicalein, providing evidence that hyaluronan-mediated motility receptor (HMMR) and androgen receptor (AR) are new molecular targets of baicalein in human cancer cells. We observed that HMMR, known to be highly associated with poor prognosis in a wide range of human cancers, was substantially downregulated by baicalein at mRNA and protein levels. Reporter assays further revealed that the suppression of HMMR by baicalein might occur through a transcriptional regulatory mechanism with the participation of Egr-1, E2F3α, and serum response factor (SRF). We also found that baicalein significantly inhibits androgenic responses in hormone-responsive prostate cancer cells, indicating that this might be attributed to the downregulation of AR promoter activity by baicalein. Additionally, baicalein markedly induced the expression of tumor suppressive miR-30C, which might be partly involved in baicalein-mediated autophagy and anti-cancer effects. Overall, our study sheds light on new diverse mechanisms of the anti-cancer effects exhibited by baicalein, implying that baicalein could be a potential therapeutic agent against human cancers and function as an inhibitor of HMMR and AR.© 2023. The Pharmaceutical Society of Korea.