Inositol hexaphosphate and paclitaxel: symbiotic treatment of oral cavity squamous cell carcinoma.
OBJECTIVE
Nuclear factor (NF)-kappaB is an early response gene that has been associated with head and neck squamous cell cancer (HNSCC) progression. NF-kappaB activation is induced by some chemotherapy agents, including paclitaxel. The activation of this gene can be correlated with apoptosis resistance. Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate. NF-kappaB levels were evaluated in oral cavity HNSCC lines after treatment with paclitaxel and IP6, alone and in combination. Resulting levels of cell death and apoptosis were assessed, and conclusions are drawn regarding a possible synergistic relationship between paclitaxel and IP6.


METHODS
NF-kappaB activation in cancer cells treated with paclitaxel and IP6, alone and in combination, was measured by transient transfection, and results were interpreted by luminometry. Cell proliferation of treated cells was measured by MTT assay. Cell viability and apoptosis of cancer cells treated with paclitaxel and IP6 combinations were quantitated by trypan blue staining and Caspase-Glo 3/7 assay, respectively.


RESULTS
IP6 was observed to significantly downregulate NF-kappaB activation in both NA and CA-9-22 oral cavity HNSCC cell lines. Paclitaxel treatments caused increased NF-kappaB activation in the same cell lines. IP6 was observed to mitigate paclitaxel-induced NF-kappaB activation in the CA-9-22 cell line. IP6, when combined with paclitaxel, reduces CA-9-22 cell proliferation, increases cell death, and increases apoptosis, when compared with treatment with paclitaxel alone.


CONCLUSIONS
IP6 reduces paclitaxel induced NF-kappaB activation and increases paclitaxel-mediated cell killing and apoptosis. As a well-tolerated and safe supplement, IP6 deserves further study in the treatment of oral cavity squamous cell carcinoma.
Janus
Seth C
SC
Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota 55455, USA. janu0003@umn.edu
Weurtz
Beverly
B
Ondrey
Frank G
FG
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D018450:Disease Progression; D004357:Drug Synergism; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage; D010833:Phytic Acid / Q000008:administration & dosage
D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D010833:Phytic Acid; D017239:Paclitaxel