Abstract
To investigate the effects of betaine on HeLa cell growth and apoptosis and molecular mechanisms. Concentrations of 0.1, 1.0, 5.0, 20.0, 100.0 mg/ml of betaine were used to evaluate the anticancer efficacy for HeLa cells respectively, and MCF-10A was also detected as a normal diploid cell control. We found that proliferation of HeLa cells was inhibited significantly upon exposure to increasing betaine levels with the MTT test (p<0.05). The percentage of S phase cells in the low dose groups (< 5mg/ml) were distinctly higher than in high dose groups, and the rates of Sub-G1 phase were the opposite (p<0.01); A high concentration of betaine (>5.0mg/ml) significantly promoted the apoptosis of HeLa cells (p<0.01). SOD activities of the low dose groups were slightly higher than the control group (p<0.05) and there were obvious synchronicity and correlation among the expression of promoting apoptosis genes Bax, P53, Caspase 3 and apoptosis suppression gene Bcl-2. In response to an apoptosis-inducing stimulus, p53 and cyclin D1 could be activated with blockage of the cell cycle at G1/S or S/G2 checkpoints. Our data showed that betaine could promote HeLa cells proliferation in vitro at low concentrations.In contrast, high concentrations could significantly inhibit cell growth and migration, and induce apoptosis of HeLa cells through caspase 3 signaling and further promoted necrosis. This might imply that betaine exhibits tumoricidal effects and acts as a biological response modifier in cancer treatment by inducing apoptosis and cell cycle arrest in a dose and time-dependent manner.
Highlights
Cervical cancer is the third most common malignancies and the fourth leading cause of cancer-related mortality in women worldwide, accounting for 9% (529,800) of the total new cases and 8% (275,100) of the total cancer deaths among females in 2008 (Jemal et al, 2011)
Effect of Betaine on Cells apoptosis of Human cervical cancer (HeLa) cells There were no significant difference about rates of apoptosis between low-dose groups and negative control at 24-96h (p>0.05), while high-dose groups significantly induced the apoptosis of HeLa cells with increasing concentrations of betaine (p
Betaine showed similar effect for normal diploid MCF-10A cells, apoptosis rate increased rapidly with the increasing of incubation time at 5.0mg/ml. These results indicated that high dose betaine significantly inhibited growth and promoted apoptosis with increasing betaine concentration was due to the cytotoxic action
Summary
Cervical cancer is the third most common malignancies and the fourth leading cause of cancer-related mortality in women worldwide, accounting for 9% (529,800) of the total new cases and 8% (275,100) of the total cancer deaths among females in 2008 (Jemal et al, 2011). Numerous phytonutrients derived from edible plants are the foremost prospective agents reported to interfere with different stages of carcinogenesis and could reduce 7-31% of all cancers worldwide (Surh, 2003; Tan et al, 2011). Since 1999, the treatment of cervical cancer has involved comprehensive treatment that combines surgery and radiotherapy with chemotherapy (Hamed et al, 2012; Lai et al, 2013; Okazawa et al, 2013). Much of our understanding about fundamental cell physiology and cancer biology is due to HeLa cell research. Two Nobel prizes have been awarded for research involving HeLa cells, namely the link between human papilloma virus and cervical cancer (Landry et al, 2013). During the last 10 years, HeLa has been used as a model system to discover genes involved in mitosis/cytokinesis (Neumann et al, 2010), to investigate microarray-based gene expression profiling (Hnilicova et al, 2011), and for a combined deep proteome and transcriptome analysis (Nagaraj et al, 2011)
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