Reversal of Drug-induced Gingival Overgrowth by UV-mediated Apoptosis

Objectives: Gingival Overgrowth (GO) is an undesirable result of certain classes of drugs including, immunosuppressant, Cyclosporine A (CsA). The histopathology of GO shows, (i)hyperplasia of the gingival epithelium, or (ii)expansion of the connective tissue with increased collagen production, or (iii)a combination of both. Factors such as age, gender, oral hygiene status, duration and dosage of therapy also influence onset and severity of GO. One of the mechanisms behind uncontrolled cell proliferation in drug-induced GO is inhibition of apoptotic pathways, with a consequent effect on normal cell turnover. The objective of our study was to determine if UV photo-treatment would activate apoptosis in drug-induced GO, thereby potentially reversing the condition. Our study validates a limited use of photo-therapy as a viable, non-surgical option for patients with certain forms of GO.
Methods: Human gingival epithelial progenitor cells (HGF-1) were exposed to either 200ng/ml or 400ng/ml CsA and allowed to overproliferate for 3, 6, and 9 days, followed by 254nm UV radiation for 2, 5 or 10 minutes (N=6). Naïve (no CsA or UV), negative (UV, no CsA) and positive controls (CsA, no UV) were designated. Prior to UV treatment, growth media was replaced with 1M PBS to prevent absorption of UV radiation by serum proteins, and cells were incubated in growth media for 24 hours post-UV before processing for TUNEL assay, Western blot, cell proliferation assays or immunofluorescence.
Results: As expected, our data showed a temporal increase in proliferation of HGF-1 cells under the influence of CsA. Interestingly, the 200ng/ml dose was more effective in causing overproliferation. 10min UV treatment resulted in significant reduction in cell numbers, as evidenced by counts and proliferation assays. TUNEL assay and Western blot analyses confirmed apoptosis following UV treatment.
Conclusions: Therefore, UV phototherapy could be an effective, non-invasive approach to manage some forms of drug-induced GO.