Kurarinol induces hepatocellular carcinoma cell apoptosis through suppressing cellular signal transducer and activator of transcription 3 signaling.

Abstract

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.

• Authors: Guangwen Shu, Jing Yang, Wenhao Zhao, Chan Xu, Zongguo Hong, Zhinan Mei, Xinzhou Yang
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 281 Issue 2 Pg. 157-65 (Dec 01 2014) ISSN: 1096-0333 [Electronic] United States
• PMID: 24997323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014. Published by Elsevier Inc.

Chemical References

• Antineoplastic Agents, Phytogenic
• Flavonoids
• STAT3 Transcription Factor
• STAT3 protein, human
• Stat3 protein, mouse
• kurarinol

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, genetics, metabolism, pathology)
• Dose-Response Relationship, Drug
• Down-Regulation
• Flavonoids (pharmacology)
• Gene Expression Regulation, Neoplastic
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, genetics, metabolism, pathology)
• Male
• Mice
• STAT3 Transcription Factor (genetics, metabolism)
• Signal Transduction (drug effects)
• Transcription, Genetic
• Transfection
• Tumor Burden