Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 281, Issue 2, Pages 157-165Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2014.06.021
Keywords
Apoptosis; Hepatocellular carcinoma; Kurarinol; Anti-cancer; STAT3; Signal transduction
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Funding
- Natural Science Foundation of China [31301147, 81102798]
- Chenguang Planning of the Natural Science Foundation of Wuhan City [2013070104010029]
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Kurarinol is a flavonoid isolated from roots of the medical plant Sophora flavescens. However, its cytotoxic activity against hepatocellular carcinoma (HCC) cells and toxic effects on mammalians remain largely unexplored. Here, the pro-apoptotic activities of kurarinol on HCC cells and its toxic impacts on tumor-bearing mice were evaluated. The molecular mechanisms underlying kurarinol-induced HCC cell apoptosis were also investigated. We found that kurarinol dose-dependently provoked HepG2, Huh-7 and H22 HCC cell apoptosis. In addition, kurarinol gave rise to a considerable decrease in the transcriptional activity of signal transducer and activator of transcription 3 (STAT3) in HCC cells. Suppression of STAT3 signaling is involved in kurarinol-induced HCC cell apoptosis. In vivo studies showed that kurarinol injection substantially induced transplanted H22 cell apoptosis with low toxic impacts on tumor-bearing mice. Similarly, the transcriptional activity of STAT3 in transplanted tumor tissues was significantly suppressed after kurarinol treatment. Collectively, our current research demonstrated that kurarinol has the capacity of inducing HCC cell apoptosis both in vitro and in vivo with undetectable toxic impacts on the host Suppressing STAT3 signaling is implicated in kurarinol-mediated HCC cell apoptosis. (C) 2014 Published by Elsevier Inc.
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