Preferential inhibition of hepatocellular carcinoma by the flavonoid Baicalein through blocking MEK-ERK signaling

Liang,Rong-Rui; Zhang,Shu; Qi,Jun-An; Wang,Zhi-Dong; Li,Jun; Liu,Pei-Jun; Huang,Chen; Le,Xiao-Feng; Yang,Jun; Li,Zong-Fang

doi:10.3892/ijo.2012.1510

Preferential inhibition of hepatocellular carcinoma by the flavonoid Baicalein through blocking MEK-ERK signaling

Authors:
- Rong-Rui Liang
- Shu Zhang
- Jun-An Qi
- Zhi-Dong Wang
- Jun Li
- Pei-Jun Liu
- Chen Huang
- Xiao-Feng Le
- Jun Yang
- Zong-Fang Li
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Affiliations: Department of General Surgery, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710004, P.R. China, Engineering Research Center of Biotherapy and Translational Medicine of Shaanxi Province, Xi'an Jiaotong University, Xi'an, P.R. China, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Published online on: June 6, 2012 https://doi.org/10.3892/ijo.2012.1510
Pages: 969-978

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Abstract

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.

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