Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation.

Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation.
AuthorsYa-Hsin Cheng, Lih-Ann Li, Pinpin Lin, Li-Chuan Cheng, Chein-Hui Hung, Nai Wen Chang, Chingju Lin
JournalToxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 263 Issue 3 Pg. 360-7 (Sep 15 2012) ISSN: 1096-0333 [Electronic] United States
PMID22820424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Inc. All rights reserved.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Flavanones
  • Receptors, Aryl Hydrocarbon
  • Retinoblastoma Protein
  • Cyclin D1
  • baicalein
  • Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology)
  • Carcinoma, Squamous Cell (drug therapy, pathology)
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cyclin D1 (drug effects, metabolism)
  • Dose-Response Relationship, Drug
  • Flavanones (administration & dosage, pharmacology)
  • G1 Phase Cell Cycle Checkpoints (drug effects)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Mouth Neoplasms (drug therapy, pathology)
  • Phosphorylation (drug effects)
  • Receptors, Aryl Hydrocarbon (metabolism)
  • Retinoblastoma Protein (metabolism)

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