Inhibitory effects of cucurbitacin B on laryngeal squamous cell carcinoma.

Abstract

Cucurbitacins are compounds isolated from various plant families, which have been used as folk medicines for centuries in countries such as India and China because of their wide spectrum of pharmacological activities such as cytotoxic, anti-inflammatory, and anticancer effects. Accumulated evidences have shown that cucurbitacin B inhibits the growth of numerous human cancer cell lines and tumor xenografts. To determine whether cucurbitacin B can inhibit the growth of laryngeal squamous cell carcinoma, in the present study we investigated the antitumor effect of cucurbitacin B on Hep-2 cells. Hep-2 cells were treated with different concentrations of cucurbitacin B for different time. Cell proliferation, cell cycle distribution, and cell apoptosis were evaluated using MTT assay, flow cytometry, and fluorescent microscopy. It was found that cucurbitacin B exhibited significant efficacy in growth inhibition, cell cycle arrest at G2/M phase, and apoptosis induction in a dose- and time-dependent manner. Measuring the modulation of regulators in the cell cycle, apoptosis and signal transductions by Western blot analysis showed that the effect of cucurbitacin B was due to suppression of the expression of p-STAT3, Bcl-2, and cyclin B1. Moreover, in vivo studies were performed in a mouse xenograft model, where cucurbitacin B inhibited tumor growth in a dose-dependent manner. In conclusion, the antitumor effect of cucurbitacin B on Hep-2 cells was due to the induction of cell cycle arrest as well as apoptosis. The possible mechanisms underlying the action might be attributed to the suppression of STAT3 phosphorylation. This investigation suggests a potential clinical application of cucurbitacin B for the treatment of laryngeal cancer patients.

• Authors: Tingyan Liu, Meixia Zhang, Hongliang Zhang, Chunyan Sun, Yihui Deng
• Journal: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery (Eur Arch Otorhinolaryngol) Vol. 265 Issue 10 Pg. 1225-32 (Oct 2008) ISSN: 0937-4477 [Print] Germany
• PMID: 18309509 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Biomarkers, Tumor
• CCNB1 protein, human
• Ccnb1 protein, mouse
• Cyclin B
• Cyclin B1
• Proto-Oncogene Proteins c-bcl-2
• STAT3 Transcription Factor
• STAT3 protein, human
• Triterpenes
• cucurbitacin B

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (biosynthesis)
• Blotting, Western
• Carcinoma, Squamous Cell (drug therapy, metabolism, pathology)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cyclin B (biosynthesis)
• Cyclin B1
• Disease Models, Animal
• Flow Cytometry
• Humans
• Laryngeal Neoplasms (drug therapy, metabolism, pathology)
• Mice
• Mice, Nude
• Microscopy, Fluorescence
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
• STAT3 Transcription Factor (biosynthesis)
• Triterpenes (therapeutic use)
• Tumor Cells, Cultured