The metabolite 7β-hydroxychlesterol induces apoptosis in malignant head and neck cancer cells and acts synergistically with cisplatin

D Thurnher MD^a, BM Erovic MD^a, L Vormittag MD^a, H Ulrich-Pur MD^b, C Eder-Czembirek MD^c, K Ehrenberger MD^a

^aDepartment of Otorhinolaryngology, Head and Neck Surgery, Austria, ^bDepartment of Internal Medicine, Section of Oncology, Austria, ^cDepartment of Radiotherapy and Radiobiology, Austria

Aim: The overall prognosis for patients with advanced cancer of the head and neck is still poor, and currently available therapeutic options still lack efficiency, emphasizing the need for more effective substances that might be used in combination with surgery, chemotherapy and radiotherapy. As recently described the metabolite 7β-hydroxychlesterol has been found to be cytotoxic against colorectal cancer cells. Its effects against head and neck squamous cellular carcinoma cell lines have not been tested so far. Here we report for the first time that the water-soluble derivative of 7β-hydroxychlesterol is active against the head and neck squamous cellular carcinoma cell lines SCC25 and SCC9. In addition, we demonstrate that it also has synergistic effects in combination with the cytostatic agent cisplatin. Methods: Cell numbers were assayed by automated counting, cell proliferation was determined with a XTT-assay, fluorescence -immunostaining of apoptotic cells was done with the CytoDeath M30 antibody and expression pattern of Bcl-2 family members was analysed in Western blots. Results: In both HNSCC cell lines 7β-hydroxychlesterol caused a dose-dependent reduction of cell proliferation via the induction of apoptosis. Furthermore, a synergistic effect regarding growth inhibition was observed when 7β-hydroxychlesterol was combined with cisplatin. Western blot analysis of the expression of Bcl-2 family members in these cells showed a suppression of the expression of the anti-apoptotic protein Mcl-1 under treatment with 7β-hydroxychlesterol. Conclusion: These data clearly demonstrate that 7β-hydroxychlesterol has activity against HNSCC cells.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 991 (Synergistic therapies).