IADR Abstract Archives

Old Drug as a New Therapy for Salivary Gland Tumor

Background: Salivary gland cancers are a highly diverse group of tumors associated with significant morbidity under current diagnosis and treatment. Metformin is one of the most commonly prescribed drugs for Type II diabetes. Accumulating epidemiological reports indicate that the anti-neoplastic effects of metformin are mediated by directly inhibiting cancer cell growth in many types of cancers. It is yet not known if metformin inhibits the growth of salivary gland tumors.

Objective: We tested the inhibitory effects of metformin on a human parotid gland tumor cells (HSY cell line) and explored the epigenetic signature associated with salivary gland tumor malignancy.

Method: The effect of metformin on HSY cell proliferation was determined by crystal violet staining and cell number counting. Immunocytochemistry was performed on HSY cells to determine the levels of MYC and pSTAT. RNA was extracted from primary salivary gland tumors, normal tissues and cells. Gene expression levels were determined by realtime PCR using the human Epigenetic Chromatin Modification Enzymes PCR Array or specific primers for genes of interest.

Results: Metformin reduced HSY cell proliferation ~20% after 72h. The expression of MYC oncogene and epigenetic-modifier genes increased in human salivary gland tumors compare to normal tissue. Administration of metformin reduced MYC oncogene expression was associated with reduction in phosphorylation of STAT3 and several K (lysine) acetyltransferases, which are over-expressed in primary salivary tumors.

Conclusions: Suppression of MYC oncogene, pSTAT3 and acetyltransferases suggests that metformin inhibits salivary gland tumor cell growth by inhibiting proliferation, apoptosis and reversing epigenetic enzyme expression to normal levels. Identification of the epigenetic alterations associated with salivary gland tumors could provide a biomarker signature to be used as a diagnostic for early stage tumor initiation. Further investigation will be necessary to support this hypothesis.

IADR/AADR/CADR General Session
2013 IADR/AADR/CADR General Session (Seattle, Washington)
Seattle, Washington
2013
107
Salivary Research
  • Matsumura, Satoko  ( New York University College of Dentistry, New York, NY, USA )
  • Kurago, Zoya  ( New York University, New York, NY, USA )
  • Myssiorek, David  ( New York University, New York, NY, USA )
  • Malamud, Daniel  ( New York University College of Dentistry, New York, NY, USA )
  • Li, Xin  ( New York University College of Dentistry, New York, NY, USA )
    • Oral Session
    Saliva in Health and Disease [CLINICIAN TRACK]
    03/20/2013