Department of General Surgery, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710004, P.R. China.
Int J Oncol. 2012 Sep;41(3):969-78. doi: 10.3892/ijo.2012.1510. Epub 2012 Jun 6.
Baicalein is a purified flavonoid extracted from the roots of Scutellaria baicalensis or Scutellaria radix. Although previous studies have suggested that Baicalein possesses an in vitro anti-hepatocellular carcinoma activity, its in vivo effects and mechanisms of action are still not completely understood. In this study, Baicalein at concentrations of 40-120 µM exhibited significant cytotoxicity to three hepatocellular carcinoma (HCC) cell lines but marginal cytotoxicity to a normal liver cell line in vitro. Compared to a standard chemotherapy drug, 5-fluorouracil (5-FU), Baicalein had greater effect on HCC cells but less toxicity on normal liver cells. Treatment with Baicalein dramatically reduced mitochondrial transmembrane potential, and activated caspase-9 and caspase-3. Blockade of Baicalein-induced apoptosis with a pan-caspase inhibitor partially attenuated Baicalein-induced growth inhibition in HCC. Baicalein treatment significantly inhibited tumor growth of HCC xenografts in mice. Induction of apoptosis was demonstrated in Baicalein-treated xenograft tumors by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Furthermore, Baicalein treatment dramatically decreased the levels of phosphorylation of MEK1, ERK1/2 and Bad in vitro and in vivo. Overexpression of human MEK1 partially blocked Baicalein-induced growth inhibition. Consequently, these findings suggest that Baicalein preferentially inhibits HCC tumor growth through inhibition of MEK-ERK signaling and by inducing intrinsic apoptosis.
黄芩素是从黄芩或黄芩根中提取的一种纯化黄酮类化合物。虽然先前的研究表明黄芩素有体外抗肝癌活性，但它在体内的作用和机制仍不完全清楚。在这项研究中，黄芩素在 40-120µM 的浓度下对三种肝癌（HCC）细胞系表现出显著的细胞毒性，但对体外正常肝细胞系仅有轻微的细胞毒性。与标准化疗药物 5-氟尿嘧啶（5-FU）相比，黄芩素对 HCC 细胞的作用更大，但对正常肝细胞的毒性更小。黄芩素处理显著降低了线粒体跨膜电位，并激活了 caspase-9 和 caspase-3。用泛半胱天冬酶抑制剂阻断黄芩素诱导的细胞凋亡部分减弱了黄芩素诱导的 HCC 细胞生长抑制。黄芩素处理显著抑制了 HCC 异种移植瘤在小鼠中的生长。末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）检测显示，黄芩素处理诱导了异种移植瘤中的细胞凋亡。此外，黄芩素处理在体外和体内均显著降低了 MEK1、ERK1/2 和 Bad 的磷酸化水平。人 MEK1 的过表达部分阻断了黄芩素诱导的生长抑制。因此，这些发现表明，黄芩素通过抑制 MEK-ERK 信号通路和诱导内在凋亡，优先抑制 HCC 肿瘤生长。
