Abstract
The aim of the present in vitro study was to compare the effects of synthetic and plant-derived mTOR regulators on healthy human ovarian cells. We compared the effect of two synthetic mammalian mTOR blockers MC2141 and MC2183 with that of natural/plant-derived mTOR blocker rapamycin and mTOR activator resveratrol on cultured human ovarian granulosa cells. We evaluated the accumulation of markers for the mTOR system (sirtuin 1; SIRT 1), proliferation (PCNA), and apoptosis (caspase 3) along with the expression of the transcription factor p53 by quantitative immunocytochemistry. It was observed that MC2183 but not MC2141 or rapamycin reduced SIRT 1 accumulation. MC2141, MC2183, and rapamycin inhibited the accumulation of PCNA, caspase 3, and p53. On the contrary, resveratrol promoted the accumulation of SIRT-1, PCNA, caspase 3, and p53. We have demonstrated the involvement of the mTOR system in the regulation of healthy human ovarian cell proliferation and apoptosis for the first time and indicated that the action of mTOR regulators on ovarian cell apoptosis can be mediated by p53. We have further shown that mTOR regulators can affect ovarian functions without any changes in SIRT-1 accumulation and that the stimulatory effects of resveratrol on analyzed ovarian cell functions are opposite to the inhibitory effects of rapamycin and synthetic mTOR blockers.