Acid sphingomyelinase activity as an indicator of the cell stress in HPV-positive and HPV-negative head and neck squamous cell carcinoma

Med Oncol. 2018 Mar 21;35(4):58. doi: 10.1007/s12032-018-1117-4.

Abstract

Human papillomavirus (HPV) infection, especially HPV-16 and HPV-18, has been increasingly associated with head and neck squamous cell carcinoma. The treatment of HPV-positive squamous cell carcinoma has a better response to both radiotherapy and chemotherapy and presents a better prognosis for the patient. Defining the underlying mechanism of the difference might help in developing future treatment options and could be an important factor in personal therapy planning. Endogenously secreted acid sphingomyelinase (ASMase) levels in the cellular stress caused by irradiation and cisplatin were investigated. MTT assay was performed to evaluate the viability of the treated cells. Keratinocytes were used to evaluate the effects of radiation on normal tissues. Irradiation caused a dose-dependent increase in ASMase activity in both SCC9 HPV-negative, and UDSCC2 HPV-positive cells. ASMase activity in UDSCC2 cells was significantly higher than that in SCC9 cells. UDSCC cells were more sensitive to cisplatin treatment than SCC cells, and the dose-response in the activity was observed in long-time treatments when high doses of cisplatin were used. The results of the current study have clearly showed that HPV positivity should be considered as one of the determinative factors which should be considered when tumor treatments are planned. However, further studies are needed to determine the differences in cellular responses and pathways among HPV-negative and HPV-positive cells.

Keywords: Acid sphingomyelinase; Cell stress; HPV; Squamous cell carcinoma.

MeSH terms

  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / virology*
  • Cell Line, Tumor
  • Cell Shape / drug effects
  • Cisplatin / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Activation / radiation effects
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / enzymology*
  • Head and Neck Neoplasms / radiotherapy
  • Head and Neck Neoplasms / virology*
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / enzymology
  • Keratinocytes / pathology
  • Keratinocytes / radiation effects
  • Papillomavirus Infections / enzymology*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Sphingomyelin Phosphodiesterase / metabolism*
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Sphingomyelin Phosphodiesterase
  • Cisplatin