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

Guo, Yu; Xu, Li; Ding, Zhijie; Liao, Ya-Ping; Wang, Haiping; Lan, Zhihui; Guan, Weijun; Liu, Changqing

doi:10.7314/apjcp.2015.16.8.3195

Cited by 19 publications

(17 citation statements)

References 21 publications

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“…The G 2 /M checkpoint allows the cell to repair DNA damage before entering mitosis and is the most conspicuous target for many anticancer drugs that would cause cell death through the induction of apoptosis [54]. In this study, 4% betaine treatment induced cell cycle arrest in G 2 /M phase, preventing a further proliferation of cancer cells, as similarly observed in HeLa cells [35], in correlation with the observed decrease of cell viability seen in the MTT assay. 11% of the cell distribution found in the sub-G 1 phase represents the population of cells in apoptosis or necrosis with fragmented nuclear DNA [55].…”

Section: Discussionsupporting

confidence: 53%

“…When betaine was combined with C-PC, this number decreased to 6.71%. In conclusion, it would appear that 4% betaine induced cell cycle arrest in G 2 /M phase and prevented further proliferation of cancer cells, as similarly observed in HeLa cells [35]. 80 μ g·L −1 of C-PC only slightly influenced the cell cycle by increasing G 1 [36] and decreasing S phase cells.…”

Section: Resultsmentioning

confidence: 52%

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Study of the Effects of Betaine and/or C-Phycocyanin on the Growth of Lung Cancer A549 CellsIn VitroandIn Vivo

Bingula

Dupuis

Pichon

et al. 2016

Journal of Oncology

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We investigated the effects of betaine, C-phycocyanin (C-PC), and their combined use on the growth of A549 lung cancer both in vitro and in vivo. When cells were coincubated with betaine and C-PC, an up to 60% decrease in viability was observed which is significant compared to betaine (50%) or C-PC treatment alone (no decrease). Combined treatment reduced the stimulation of NF-κB expression by TNF-α and increased the amount of the proapoptotic p38 MAPK. Interestingly, combined treatment induced a cell cycle arrest in G2/M phase for ~60% of cells. In vivo studies were performed in pathogen-free male nude rats injected with A549 cells in their right flank. Their daily food was supplemented with either betaine, C-PC, both, or neither. Compared to the control group, tumour weights and volumes were significantly reduced in either betaine- or C-PC-treated groups and no additional decrease was obtained with the combined treatment. This data indicates that C-PC and betaine alone may efficiently inhibit tumour growth in rats. The synergistic activity of betaine and C-PC on A549 cells growth observed in vitro remains to be further confirmed in vivo. The reason behind the nature of their interaction is yet to be sought.

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Section: Discussionsupporting

confidence: 53%

Section: Resultsmentioning

confidence: 52%

Study of the Effects of Betaine and/or C-Phycocyanin on the Growth of Lung Cancer A549 CellsIn VitroandIn Vivo

Bingula

Dupuis

Pichon

et al. 2016

Journal of Oncology

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“…Figure 7C shows representative Western blot from the extracts of HCT-116 cells stimulated with IL-4 and exposed to AS1517499, where a reduction up to 60% of STAT6 phosphorylation was detected. Additionally, it has been reported in cervical cancer that Trimethylglycine is able to increase the levels of P53 protein [42], thus, in order to determine whether a similar effect occurred in our system, we performed immunofluorescence assays on HCT-116 cells and detected a high expression of P53 in cells exposed to Trimethylglycine in comparison to the control and IL-4 stimulated cells ( Figure 7D). Together these findings confirm that Trimethylglycine is able to inhibit STAT6 phosphorylation and favor P53 expression.…”

Section: Trimethylglycine Decreases Stat6 Phosphorylation In Human Epmentioning

confidence: 53%

“…However, at present, we cannot rule out that an increase in ERK1/2 phosphorylation by Trimethylglycine treatment could be a compensatory or alternative mechanism to escape cell death induced by adjuvant therapy with 5-FU. We showed in our in vitro model of human colon cancer cells that exposure to Trimethylglycine partially inhibits STAT6 phosphorylation that leads to high expression of P53 protein, which may be an additional marker of apoptosis induced by Trimethylglycine [42].…”

Section: Discussionmentioning

confidence: 70%

Use of STAT6 Phosphorylation Inhibitor and Trimethylglycine as New Adjuvant Therapies for 5-Fluorouracil in Colitis-Associated Tumorigenesis

Mendoza

Sánchez-Barrera

Callejas

et al. 2020

IJMS

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Colorectal cancer (CRC) is one of the most widespread and deadly types of neoplasia around the world, where the inflammatory microenvironment has critical importance in the process of tumor growth, metastasis, and drug resistance. Despite its limited effectiveness, 5-fluorouracil (5-FU) is the main drug utilized for CRC treatment. The combination of 5-FU with other agents modestly increases its effectiveness in patients. Here, we evaluated the anti-inflammatory Trimethylglycine and the Signal transducer and activator of transcription (STAT6) inhibitor AS1517499, as possible adjuvants to 5-FU in already established cancers, using a model of colitis-associated colon cancer (CAC). We found that these adjuvant therapies induced a remarkable reduction of tumor growth when administrated together with 5-FU, correlating with a reduction in STAT6-phosphorylation. This reduction upgraded the effect of 5-FU by increasing both levels of apoptosis and markers of cell adhesion such as E-cadherin, whereas decreased epithelial–mesenchymal transition markers were associated with aggressive phenotypes and drug resistance, such as β-catenin nuclear translocation and Zinc finger protein SNAI1 (SNAI1). Additionally, Il-10, Tgf-β, and Il-17a, critical pro-tumorigenic cytokines, were downmodulated in the colon by these adjuvant therapies. In vitro assays on human colon cancer cells showed that Trimethylglycine also reduced STAT6-phosphorylation. Our study is relatively unique in focusing on the effects of the combined administration of AS1517499 and Trimethylglycine together with 5-FU on already established CAC which synergizes to markedly reduce the colon tumor load. Together, these data point to STAT6 as a valuable target for adjuvant therapy in colon cancer.

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“…Although some scientific studies indicated that betaine has protective effects on liver and cervical carcinoma cells, its effects on prostate cancer have not been investigated sufficiently. Several in vitro and in vivo studies confirmed that betaine has a number of anticancer effects, such as inhibition of carcinogen activation, cancer cell proliferation, angiogenesis, and metastasis (Guo et al 2015). In addition to the positive effects on metabolic diseases, there are also human studies reporting that betaine is also associated with various cancer, including breast, lung, liver, colorectal, and nasopharyngeal (Ying et al 2013;Zeng et al 2014;Xu et al 2009;Zhou et al 2017).…”

Section: Discussionmentioning

confidence: 97%

Betaine suppresses cell proliferation by increasing oxidative stress–mediated apoptosis and inflammation in DU-145 human prostate cancer cell line

Kar

Hacıoğlu

Kaçar

et al. 2019

Cell Stress and Chaperones

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Prostate cancer is the main cause of cancer-related mortality in men around the world and an important health problem. DU-145 human prostate cancer cells provide an opportunity to investigate prostate cancer. Betaine has a number of anticancer effects, such as inactivation of carcinogens, inhibition of cancer cell proliferation, angiogenesis, and metastasis. However, there is no study investigating the effects of betaine on DU-145 cells. The aim of this study was to evaluate the effects of different concentrations of betaine on the oxidative stress, apoptosis, and inflammation on DU-145 cells. Firstly, we proved the cytotoxic activity of betaine (0 to 150 mg/ml) on DU-145 cells by using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and defined the optimal concentration of betaine. Then, by employing the doses found in MTT, the levels of antioxidant (GSH, SOD, CAT, and TAS) and oxidant (MDA and TOS) molecules, pro-inflammatory cytokines (TNF-a and IL-6), apoptotic proteins (CYCS and CASP3), and DNA fragmentation were measured. Morphological changes and apoptosis were evaluated using H&E technique, Bax and Bcl-2 immunohistochemistry. Results suggested that betaine caused oxidative stress, inflammation, inhibition of cell growth, apoptosis, and morphological alterations in DU-145 cells dose-dependently. Furthermore, treatments with increasing betaine concentrations decreased the antioxidant levels in cells. We actually revealed that betaine, known as an antioxidant, may prevent cell proliferation by acting as an oxidant in certain doses. In conclusion, betaine may act as a biological response modifier in prostate cancer treatment in a dose-dependent manner.

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

Cited by 19 publications

References 21 publications

Study of the Effects of Betaine and/or C-Phycocyanin on the Growth of Lung Cancer A549 CellsIn VitroandIn Vivo

Study of the Effects of Betaine and/or C-Phycocyanin on the Growth of Lung Cancer A549 CellsIn VitroandIn Vivo

Use of STAT6 Phosphorylation Inhibitor and Trimethylglycine as New Adjuvant Therapies for 5-Fluorouracil in Colitis-Associated Tumorigenesis

Betaine suppresses cell proliferation by increasing oxidative stress–mediated apoptosis and inflammation in DU-145 human prostate cancer cell line

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