[P1-2-05] Inhibitory effects of periodontal pathogen-derived butyrate on proliferation and metabolism differ between normal and OSSC cells
キーワード：酪酸、口腔扁平上皮癌、細胞代謝
Introduction: Butyrate, one of the major metabolites of periodontal pathogens, has been reported to have various effects on the survival, proliferation and progression of oral squamous cell carcinoma (OSCC) cells. In particular, butyrate has been reported to inhibit OSCC cell proliferation. However, the butyrate concentration in the oral cavity may fluctuate due to salivary clearance and bacterial metabolic activity. Under these circumstances, it is unclear how OSCC cells respond to butyrate with respect to proliferation and metabolic activity and how they differ from normal cells. Therefore, we aimed to investigate the effect of coexistence and pre-exposure of butyrate on proliferation and glucose metabolic activity, an essential cellular metabolic function, in normal and OSCC cells.
Materials and Methods: HaCaT (normal cell line) and HSC2, HSC3 (OSCC cell lines) were used. The effect of coexistence of butyrate (1-10 mM) on the proliferation of these cells was evaluated. In the next experiment, these cells were pre-exposed to 1-10 mM butyrate for 12-72 h in medium and then collected. Changes in glucose metabolic activity of these collected cells was analyzed with a pH-stat system, and the organic acids produced by these cells were analyzed by high performance liquid chromatography (HPLC). In addition, these cells pre-exposed to butyrate were sub-cultured in normal medium without butyrate to evaluate their growth rate.
Results and Conclusion: Co-existence with 5 mM and more butyrate remarkably inhibited proliferation of all cells, but the inhibition in OSCC cells was lower than in HaCaT cells. In addition, proliferation of HSC2 and HSC3 pre-exposed to butyrate recovered faster than HaCaT in normal medium without butyrate. Inhibition of glucose metabolic activity was observed in HaCaT and HSC3 cells coexisted with higher concentrations of butyrate, but not in HSC2. The ratio of lactate in total acid production tended to decrease in HSC3 cells. In conclusion, butyrate inhibited proliferation in both normal and OSCC cells, but OSCC cells recovered proliferative capacity more quickly than normal cells, which may assist selective growth of OSCC cells in tissue. In addition, the effect of butyrate on glucose metabolic activity differed obviously depending on cell types, even in OSCC cells. Although butyrate has been reported to inhibit OSCC cell proliferation, our results suggest that the effect of butyrate on OSCC cells may be rather less inhibitory than that on normal cells.
Conflict of Interest: None.
Materials and Methods: HaCaT (normal cell line) and HSC2, HSC3 (OSCC cell lines) were used. The effect of coexistence of butyrate (1-10 mM) on the proliferation of these cells was evaluated. In the next experiment, these cells were pre-exposed to 1-10 mM butyrate for 12-72 h in medium and then collected. Changes in glucose metabolic activity of these collected cells was analyzed with a pH-stat system, and the organic acids produced by these cells were analyzed by high performance liquid chromatography (HPLC). In addition, these cells pre-exposed to butyrate were sub-cultured in normal medium without butyrate to evaluate their growth rate.
Results and Conclusion: Co-existence with 5 mM and more butyrate remarkably inhibited proliferation of all cells, but the inhibition in OSCC cells was lower than in HaCaT cells. In addition, proliferation of HSC2 and HSC3 pre-exposed to butyrate recovered faster than HaCaT in normal medium without butyrate. Inhibition of glucose metabolic activity was observed in HaCaT and HSC3 cells coexisted with higher concentrations of butyrate, but not in HSC2. The ratio of lactate in total acid production tended to decrease in HSC3 cells. In conclusion, butyrate inhibited proliferation in both normal and OSCC cells, but OSCC cells recovered proliferative capacity more quickly than normal cells, which may assist selective growth of OSCC cells in tissue. In addition, the effect of butyrate on glucose metabolic activity differed obviously depending on cell types, even in OSCC cells. Although butyrate has been reported to inhibit OSCC cell proliferation, our results suggest that the effect of butyrate on OSCC cells may be rather less inhibitory than that on normal cells.
Conflict of Interest: None.