The chemopreventive and clinically used agent curcumin sensitizes HPV (-) but not HPV (+) HNSCC to ionizing radiation, in vitro and in a mouse orthotopic model
- PMID: 22441776
- PMCID: PMC4727515
- DOI: 10.4161/cbt.19772
The chemopreventive and clinically used agent curcumin sensitizes HPV (-) but not HPV (+) HNSCC to ionizing radiation, in vitro and in a mouse orthotopic model
Abstract
Radiation therapy (RT) plays a critical role in the local-regional control of head and neck squamous cell carcinoma (HNSCC). However, the efficacy of RT in treating HNSCC is limited by severe normal tissue toxicity, predominantly mucositis. One pharmacological approach for increasing the clinical response to RT is the use of radiation response modifiers that preferentially sensitize tumor cells. Previously we demonstrated that curcumin, a natural plant polyphenol, increased the radiation sensitivity of HNSCC cells and that the observed sensitization was dependent on curcumin-mediated inhibition of thioredoxin reductase 1 (TxnRd1) a key cytosolic regulator of redox-dependent signaling. Here, we examined curcumin-induced radiation sensitization in HNSCC cell lines with differing HPV status and expressing different levels of TxnRd1, in vitro. The intrinsic radiation resistance of the HPV (-) cell lines was significantly higher than the HPV (+) cell lines used in our study. Notably, all of the HPV (-) cell lines expressed high levels of TxnRd1 and exhibited higher intrinsic resistance to RT. While curcumin was effective at increasing the radiation response of the resistant HPV (-) cell lines it had no effect on the HPV (+) cells. Based on these findings we employed an orthotopic, HPV (-) HNSCC tumor model in athymic nude mice to examine the effect of combining curcumin with fractionated RT, in vivo. The combination of curcumin feeding and fractionated RT had a significant effect on tumor doubling time and overall animal survival. We therefore propose that curcumin and RT should be considered as a first line treatment of HPV (-) HNSCC.
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References
-
- Hunter KD, Parkinson EK, Harrison PR. . Profiling early head and neck cancer. Nat Rev Cancer 2005; 5:127 - 35; http://dx.doi.org/10.1038/nrc1549; PMID: 15685196 - DOI - PubMed
-
- Leemans CR, Braakhuis BJM, Brakenhoff RH. . The molecular biology of head and neck cancer. Nat Rev Cancer 2011; 11:9 - 22; http://dx.doi.org/10.1038/nrc2982; PMID: 21160525 - DOI - PubMed
-
- Marur S, D’Souza G, Westra WH, Forastiere AA. . HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 2010; 11:781 - 9; http://dx.doi.org/10.1016/S1470-2045(10)70017-6; PMID: 20451455 - DOI - PMC - PubMed
-
- Gillison ML. . Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol 2004; 31:744 - 54; http://dx.doi.org/10.1053/j.seminoncol.2004.09.011; PMID: 15599852 - DOI - PubMed
-
- Hobbs CGL, Sterne JAC, Bailey M, Heyderman RS, Birchall MA, Thomas SJ. . Human papillomavirus and head and neck cancer: a systematic review and meta-analysis. Clin Otolaryngol 2006; 31:259 - 66; http://dx.doi.org/10.1111/j.1749-4486.2006.01246.x; PMID: 16911640 - DOI - PubMed
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