S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylation Status of <i>c-myc </i>and H-ras in Human Gastric Cancer and Colon Cancer

Luo, Jin; Li, Yanni; Wang, Fei; Zhang, Weiming; Geng, Xin

doi:10.7150/ijbs.6.784

Cited by 103 publications

(78 citation statements)

References 42 publications

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“…Since use of SAM in a therapeutic setting has not yet been proven when SAM is combined with several anticancer drugs, we examined whether the use of SAM is a regulatory mechanism for the direct modulation of the anticancer effect of DNA-damaging drugs. It has been reported that SAM has inhibitory effects on some carcinoma cells, as well as the proliferation and migration of HUVEC cells at high concentrations (10,26). In our analysis, however, SAM did not exhibit distinct effects on cell growth in A549 lung cancer cells at concentrations ranging up to 40 µg/ml.…”

Section: Discussioncontrasting

confidence: 45%

S-adenosyl methionine specifically protects the anticancer effect of 5-FU via DNMTs expression in human A549 lung cancer cells

Ham

Lee

Kim

2012

Molecular and Clinical Oncology

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Abstract. Cellular methylation is associated with stabilization of the chromatin structure. S-adenosyl methionine (SAM), a metabolite of methionine metabolism, is the methyl donor of essential cellular methyltransferase reactions. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyl tetrazolium bromide (MTT) assay, we found that combination treatment of SAM and 5-fluorouracil (5-FU) specifically protected the anticancer effect of 5-FU, whereas the combination of SAM and cisplatin had no effect. This result was confirmed by FACS analysis. The combination treatment of SAM and 5-FU significantly decreased the dead cell population, while the G1 cell population was slightly increased, suggesting that protection of SAM is not associated with the cell cycle arrest of DNA-damaging drugs. We also analyzed which cellular methylation-related proteins were involved in the protective effect. Results showed the expression of DNA methyltransferases (DNMTs) was decreased with 5-FU alone but was increased with the combination treatment of SAM and 5-FU, suggesting that SAM protects the anticancer effect of 5-FU by regulating the expression of DNMTs. Taken together, the results indicated that SAM specifically modulates the anticancer effect of the DNA damage agent 5-FU and this may be modulated by aberrant DNA methylation.

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Section: Discussioncontrasting

confidence: 45%

S-adenosyl methionine specifically protects the anticancer effect of 5-FU via DNMTs expression in human A549 lung cancer cells

Ham

Lee

Kim

2012

Molecular and Clinical Oncology

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“…Due to the suppression of PA biosynthetic genes, there will be a rise in SAM concentration. Inhibition of the growth of human gastric cancer and colon cancer by SAM treatment has been reported [49]. It was stated that a global DNA hypomethylation might activate oncogene transcription and SAM serves as a methyl donor in biological transmethylation events.…”

Section: Discussionmentioning

confidence: 98%

Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line

et al. 2015

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The diamine putrescine and polyamines, spermidine (triamine) and spermine (tetraamine) are small organic polycations that play an indispensable role in key cellular processes such as the regulation of growth, differentiation, and macromolecular functions. Elevated levels of polyamines (PAs) have been shown to be one of the major factors involved in carcinogenesis. In this study, specific silencing of the expression of three genes of PA biosynthesis pathway, ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC), and spermidine synthase (SPDSYN) was achieved using RNA interference in MCF 7 breast cancer cell line. For optimizing the effective small interfering nucleic acid (siNA), three variants of ODC siNA [siRNA, locked nucleic acid (LNA)-modified siRNA, and siHybrid (RNA and DNA hybrid)] were used and a dose- and time-dependent study was conducted. The PA biosynthetic genes were targeted individually and in combination. RNAi-mediated reduction in the expression of PA biosynthesis genes resulted in distorted cell morphology, reduced cancer cell viability, and migration characteristic. The most promising results were observed with the combined treatment of siSPDSYN and siODC with 83 % cell growth inhibition. On analyzing the messenger RNA (mRNA) expression profile of the cell cycle and apoptosis-related genes, it was observed that RNAi against PA biosynthetic genes downregulated the expression of CDK8, CCNE2, CCNH, CCNT1, CCNT2, CCNF, PCNA, CCND1, and CDK2, and upregulated the expression of E2F4, BAX, FAS, TP53, CDKN1A, BAK1, CDKN1B, ATM, GRANB, and ATR genes when compared with control-transfected cells. These results suggest that the targeting polyamine biosynthesis through RNAi approach could be a promising strategy for breast cancer therapy and might be extended for therapy of other cancers.

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“…For example, an intermediate metabolite of the Kreb's cycle, fumarate acid, displays antioxidant properties by increasing the expression of Nrf2, a transcription factor that induces the expression of antioxidant enzymes [21]. Kynurenines or the methylthioadenosine precursor S-Adenosyl-Methionine are other examples, both able to modulate cell proliferation and survival in different pathological situations [22][23][24]. In this study we provide in vitro and in vivo evidence that methylthioadenosine promotes remyelination and protects against demyelination in two different model of demyelination.…”

Section: Discussionmentioning

confidence: 99%

Methylthioadenosine promotes remyelination by inducing oligodendrocyte differentiation

Moreno

Vila

Fernández-Díez

et al. 2017

Mult Scler Demyelinating Disord

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Background: Methylthioadenosine is a metabolite of the polyamine pathway that modulates methyltransferase activity, thereby influencing DNA and protein methylation. Since methylthioadenosine produces neuroprotection in models of inflammation, ischemia and epilepsy, we set out to evaluate the role of methylthioadenosine in promoting remyelination, a process that will protect axons in demyelinating diseases and that will aid functional recovery.

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S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylation Status of c-myc and H-ras in Human Gastric Cancer and Colon Cancer

Cited by 103 publications

References 42 publications

S-adenosyl methionine specifically protects the anticancer effect of 5-FU via DNMTs expression in human A549 lung cancer cells

S-adenosyl methionine specifically protects the anticancer effect of 5-FU via DNMTs expression in human A549 lung cancer cells

Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line

Methylthioadenosine promotes remyelination by inducing oligodendrocyte differentiation

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