Z Phytother 2006; 27 - V31
DOI: 10.1055/s-2006-954897

Inhibition of TCF-signalling by triterpenoids from Boswellia carterii induces G0/G1 checkpoint arrest and apoptosis in human prostate cancer cells

T Syrovets 1, AC Estrada 1, B Büchele 1, T Simmet 1
  • 1Department of Pharmacology of Natural Products & Clinical Pharmacology, University of Ulm, 89081 Ulm, Germany

Prostate cancer (PC) is one of the most common and deadly cancer types in men. Triterpenoids such as acetyl-11-keto-β-boswellic acid (AKβBA) and 3-keto-tirucallic acid (KTA) induce accumulation of PC cells in the G0/G1 phase followed by induction of apoptosis. Here, we further analyzed the molecular mechanisms involved in the PC cell death induced by AKβBA and KTA.

The retinoblastoma protein (RB), a tumor suppressor controlling G1 to S-phase transition, is activated by phosphorylation. Treatment of PC cells with AKβBA and KTA led to RB dephosphorylation. The phosphorylation of RB is controlled by cyclin/cdk complexes containing cyclin D1, cyclin E and cdk4, yet AKβBA and KTA had no effect neither on cyclin E nor on cdk4 expression. The levels of the cdk inhibitors p21Waf1/Cip1 and p27Kip1 were not affected either. However, both AKβBA and KTA induced a time- and concentration-dependent transcriptional down-regulation of the cell cycle regulator cyclin D1, which is regulated by the transcription factors NF-κB and TCF. AKβBA and KTA inhibited the nuclear translocation of the NF-κB subunit p65. The TCF transcription factor is regulated by interaction with β-catenin. The levels of β-catenin remained unaffected by treatment of the PC cells with both triterpenoids. However, AKβ-BA and KTA inhibited the phosphorylation of β-catenin at Ser45.

Subsequently, the nuclear translocation of β-catenin was significantly reduced in PC cells already within 1–3h of triterpenoid treatment.

Thus, apart from inhibition of NF-κB, down-regulation of the β-catenin phosphorylation, inhibition of the TCF-activation and of the cyclin D1 expression might contribute to the antitumor effects of Boswellia-derived triterpenoids.