vitamin-k-semiquinone-radical and Nasopharyngeal-Neoplasms

Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Taiwan. To improve the treatment of NPC, we have extensively searched for effective combination chemotherapies. Our previous studies indicated that vitamin K3 (VK3) inhibits the growth of NPC CG1 cells in vitro. In this study, we further studied the binary/ternary combined effects of VK3 with other anticancer drugs against NPC cells. The antitumor effects of different VK3 combinations against CG1 cells were determined by using MTT assay, and the combined effects were evaluated by a taibologram, a modified isobolographic method being developed in our laboratory for the analyses of binary/ternary combinations of anticancer agents. Binary combinations of VK3 with doxorubicin (DOX), vinblastine (VBL), or 5-fluorouracil (5-FU) result in synergistic effects. For three-drug combinations, a remarkable synergy was found in the combination of VK3, VBL, and 5-FU. These in vitro results will provide useful information not only for further mechanistic studies and but also for future clinical trials of VK3-based cancer chemotherapy of NPC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cell Survival; Doxorubicin; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Fluorouracil; Humans; Male; Middle Aged; Nasopharyngeal Neoplasms; Tumor Cells, Cultured; Vinblastine; Vitamin K

Vitamin K3 is known to inhibit the growth of various rodent and human tumor cells. However, the molecular mechanism of its action is still elusive. We have found that vitamin K3 induces cell cycle arrest and apoptotic cell death in nasopharyngeal carcinoma (NPC) cells, as evaluated by flow cytometry and DNA gel electrophoresis. Involvement of c-fos and c-myc proto-oncogenes and expression of their proto-oncoproteins in VK3-induced cell cycle arrest and apoptosis were also investigated. Northern blot analysis of NPC cells treated with 50 microM VK3 showed that c-fos was transiently induced for 60 min after treatment, while c-myc was persistently induced for 1-9 h after drug treatment. Western blot analysis also showed that c-Fos was induced at 4-6 h and at 1-4 h after treatment with 50 microM and 200 microM VK3 respectively, while c-Myc was induced at 1-6 h and at 4-6 h, respectively, after such treatments. These results suggest that the expression of c-fos and c-myc may play an important role in the signaling mechanism of VK3-induced growth arrest and apoptotic cell death.

Topics: Actins; Apoptosis; Carcinoma; Cell Cycle; DNA, Neoplasm; Genes, fos; Genes, myc; Humans; Nasopharyngeal Neoplasms; Tumor Cells, Cultured; Vitamin K