Betaine Effects on Morphology, Proliferation, and p53-induced Apoptosis of HeLa Cervical Carcinoma Cells in Vitro

Abstract

<br/><b>Objectives</b>: To investigate the effects of betaine on HeLa cell growth and apoptosis and molecular mechanisms.Materials and <br/><b>Methods</b>: Concentrations of 0.1, 1.0, 5.0, 20.0, 100.0 mg/ml of betaine were used to evaluate theanticancer efficacy for HeLa cells respectively, and MCF-10A was also detected as a normal diploid cell control.<br/><b>Results</b>: We found that proliferation of HeLa cells was inhibited significantly upon exposure to increasing betainelevels with the MTT test (p<0.05). The percentage of S phase cells in the low dose groups (< 5mg/ml) were distinctlyhigher than in high dose groups, and the rates of Sub-G1 phase were the opposite (p<0.01); A high concentrationof betaine (>5.0mg/ml) significantly promoted the apoptosis of HeLa cells (p<0.01). SOD activities of the lowdose groups were slightly higher than the control group (p<0.05) and there were obvious synchronicity andcorrelation among the expression of promoting apoptosis genes Bax, P53, Caspase 3 and apoptosis suppressiongene Bcl-2. In response to an apoptosis-inducing stimulus, p53 and cyclin D1 could be activated with blockageof the cell cycle at G1/S or S/G2 checkpoints. <br/><b>Conclusions</b>: Our data showed that betaine could promote HeLacells proliferation in vitro at low concentrations.In contrast, high concentrations could significantly inhibit cellgrowth and migration, and induce apoptosis of HeLa cells through caspase 3 signaling and further promotednecrosis. This might imply that betaine exhibits tumoricidal effects and acts as a biological response modifier incancer treatment by inducing apoptosis and cell cycle arrest in a dose and time-dependent manner.