Methyl-Donors Can Induce Apoptosis and Attenuate Both the Akt and the Erk1/2 Mediated Proliferation Pathways in Breast and Lung Cancer Cell Lines

Abstract

Dietary methyl-donors play important roles in physiological processes catalyzed by B vitamins as coenzymes, and are used for complementary support in oncotherapy. Our hypothesis was that methyl-donors can not only assist in tolerating cancer treatment but may also directly interfere with tumor growth and proliferation. Therefore, we investigated the proposed cancer inhibitory effects of methyl-donors (in a mixture of L-methionine, choline chloride, folic acid, and vitamin B12) on MCF7 and T47D breast cancer as well as A549 and H1650 lung cancer cell lines. Indeed, methyl-donor treatment significantly reduced the proliferation in all cell lines, possibly through the downregulation of MAPK/ERK and AKT signaling. These were accompanied by the upregulation of the pro-apoptotic Bak and Bax, both in MCF7 and H1650 cells, at reduced anti-apoptotic Mcl-1 and Bcl-2 levels in MCF7 and H1650 cells, respectively. The treatment-induced downregulation of p-p53(Thr55) was likely to contribute to protecting the nuclear localization and apoptosis inducing functions of p53. The presented features are known to improve the sensitivity of cancer therapy. Therefore, these data support the hypothesis, i.e., that methyl-donors may promote apoptotic signaling by protecting p53 functions through downregulating both the MAPK/ERK and the AKT pathways both in breast and lung adenocarcinoma cell lines. Our results can emphasize the importance and benefits of the appropriate dietary supports in cancer treatments. However, further studies are required to confirm these effects without any adverse outcome in clinical settings.

Methyl Donors Reduce Cell Proliferation by Diminishing Erk-Signaling and NFkB Levels, While Increasing E-Cadherin Expression in Panc-1 Cell Line

“…Previously, we described that methyl donors are able to induce apoptosis and attenuate proliferation pathways in breast and lung cancer cell lines [ 33 ]. In our present study, we aimed to explore if similar changes could be detectable in Panc-1 cancer cells.…”

“…We found significantly increased subG1 fraction in cell cycle analysis, which indicates apoptotic cells; therefore, we investigated the intrinsic apoptotic pathway based on our previous study [ 33 ]. We found significantly increased pro-apoptotic Bak, Puma and Caspase-9 protein levels after methyl-donor treatment, but not in the case of the cleaved Caspase-3 level.…”

“…Previously, we explored the effect of methyl donors on cell cycle and apoptosis in breast and lung cancer cell lines [ 33 ]. In our present study, we aimed to investigate these effects on a Panc-1 adenocarcinoma cell line as well.…”

"B Vitamin Intake and the Risk of Colorectal Cancer Development: A Systematic Review and Meta-Analysis of Observational Studies"

“…Therefore, there is an expectation and necessity to measure and evaluate the effects of these vitamins, compounds and products [6,7,10,38]. Several studies suggested that dietary methyl-donors and related vitamins can contribute to cancer prevention [8,[39][40][41].…”

“…Dietary intake of methyl donors (such as folate, choline, betaine, methionine and vitamin B2, B6 and B12) could have important role in cancer prevention by reducing the risk of cancer and could contribute to the success of cancer therapies and to reach better quality of life (QoL) of the patients [6][7][8]. Dietary methyl donors are food components, which provide methyl groups for the one-carbon metabolism, which consists of two main metabolic cycles: the folate cycle and the methionine cycle [9].…”