Cucurbitacin B, a small molecule inhibitor of the Stat3 signaling pathway, enhances the chemosensitivity of laryngeal squamous cell carcinoma cells to cisplatin.

Abstract

We have previously shown that the simultaneous exposure of Hep-2 cells to cucurbitacin B and docetaxel significantly enhances anticancer activity of these cells by suppressing Stat3 activation and down-regulating the expression levels of key cell cycle and anti-apoptosis regulators. In order to determine whether cucurbitacin B can also enhance the sensitivity of Hep-2 laryngeal cells to cisplatin, we treated Hep-2 cells with either cucurbitacin B, cisplatin, or the combination and evaluated these cells for proliferation, cell cycle distribution, and apoptosis. Our results demonstrate that, in comparison to single agent cucurbitacin B or cisplatin treated cells, Hep-2 cells treated with a cucurbitacin B/cisplatin combination display synergistic effects on growth inhibition, cell cycle arrest, and apoptosis induction. Western blot analysis using protein extracts from Hep-2 cells treated with cucurbitacin B, cisplatin, or the combination largely recapitulated the observations made when treated with the cucurbitacin B/docetaxel combination. More specifically, Hep-2 cell lines treated with the cucurbitacin B/cisplatin combination demonstrated a significantly reduced level of p-Stat3 in comparison with single agent treated cells. In addition, cucurbitacin B/cisplatin treated Hep-2 cells also demonstrated a significant reduction in Bcl-2 and Cyclin B1 protein levels compared to single agent cucurbitacin B or cisplatin treated cells. Xenograft models containing Hep-2 cells in mice also demonstrated that this cucurbitacin B/cisplatin combination led to the synergistic inhibition of tumor growth. Taken together, these results suggest that the cucurbitacin B/cisplatin combination treatment may be a potentially useful therapeutic option for individuals diagnosed with laryngeal cancer.

• Authors: Tingyan Liu, Huaguang Peng, Meixia Zhang, Yihui Deng, Zhenghu Wu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 641 Issue 1 Pg. 15-22 (Sep 01 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20483353 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2010 Elsevier B.V. All rights reserved.

Chemical References

• Cyclin B1
• Proto-Oncogene Proteins c-bcl-2
• STAT3 Transcription Factor
• Triterpenes
• cucurbitacin B
• Cisplatin

Topics

• Animals
• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cisplatin (pharmacology)
• Cyclin B1 (metabolism)
• Down-Regulation (drug effects)
• Drug Synergism
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Laryngeal Neoplasms (metabolism, pathology)
• Mice
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Triterpenes (chemistry, pharmacology)
• Xenograft Model Antitumor Assays