Analysis of cell-cycle kinetics and sulfur amino acid metabolism in methionine-dependent tumor cell lines; the effect of homocysteine supplementation

Pavillard, Valérie; Drbal, Abedalnaser A.A.; Swaine, David J.; Phillips, Roger M.; Double, John A.; Nicolaou, Anna

doi:10.1016/j.bcp.2004.01.006

Cited by 22 publications

(21 citation statements)

References 22 publications

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“…Reversible cell-cycle block by methionine restriction has been reported in some cancer cell lines (Pavillard et al, 2004). Here, we showed that growth arrest by methionine restriction is reversible in IIICF/c cells, and that APB-positive cells are able to re-enter the cell cycle.…”

Section: Discussionsupporting

confidence: 65%

Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference

et al. 2007

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Telomerase-negative cancer cells can maintain their telomeres by a recombination-mediated alternative lengthening of telomeres (ALT) process. We reported previously that sequestration of MRE11/RAD50/NBS1 complexes represses ALT-mediated telomere length maintenance, and suppresses formation of ALT-associated promyelocytic leukemia (PML) bodies (APBs). APBs are PML bodies containing telomeric DNA and telomere-binding proteins, and are observed only in a small fraction of cells within asynchronously dividing ALT-positive cell populations. Here, we report that methionine restriction caused a reversible arrest in G 0 /G 1 phase of the cell cycle and reversible induction of APB formation in most cells within an ALT-positive population. We combined methionine restriction with RNA interference to test whether the following proteins are required for APB formation: PML body-associated proteins, PML and Sp100; telomereassociated proteins, TRF1, TRF2, TIN2 and RAP1; and DNA repair proteins, MRE11, RAD50, NBS1 and 53BP1. APB formation was not decreased by depletion of Sp100 (as reported previously) or of 53BP1, although 53BP1 partially colocalizes with APBs. Depletion of the other proteins suppressed APB formation. Because of the close linkage between ALT-mediated telomere maintenance and ability to form APBs, the eight proteins identified by this screen as being required for APB formation are also likely to be required for the ALT mechanism.

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Section: Discussionsupporting

confidence: 65%

Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference

et al. 2007

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“…Alt ho ugh, met hi o ni ne-de pendency was shown for the PC3 pros ta te can cer cell li ne, its MTHFR C677T ge noty pe was not analy zed be fo re hand, as well as its as so ci a ti on with that speci fic phe noty pe. 22 In te res tingly, we fo und that the PC3, LNCaP and He La can cer cell li nes whe re he te rozy go us; and the DU145 pros ta te ade no car ci noma cell li ne was ho mozy go us for the MTHFR C677T ge ne poly morp hisms. We the re fo re sug gest that the poly morp hic T al le le is as so ci a ted with redu ced risk of de ve lo ping pros ta te can cer, des pi te stu di es that do not sup port this vi ew.…”

Section: Discussionmentioning

confidence: 91%

“…Li mi ted supply of met hi o ni ne can ca u se a cell cycle ar rest at S and G2-M pha se in met hi o ni ne-de pen dent tu mor cells, and by this way sen si ti zes them to cell cyclespe ci fic che mot he ra pe u tic agents. 22,23 Sin ce the C677T poly morp hism dec re a ses the enz yma tic acti vity of MTHFR by 30%, it is ex pec ted to le ad to car ci no ge ne sis by af fec ting both DNA meth yla ti on and DNA synthe sis. Ac cor ding to our re sults on the MTHFR C677T poly morp hism, the ho mozy go te (T/T) ge noty pe ra ti o was hig her in the study gro up; whe re as, the he te rozy go te (C/T) ge noty pe ra ti o was hig her in the con trol gro up.…”

Section: Discussionmentioning

confidence: 99%

Effects of the Catechol-O-Methyltransferase Val108/158Met and Methylenetetrahydrofolate Reductase C677T Gene Polymorphisms on Prostate Cancer Susceptibility

Kosova¹,

Özel²,

Kaymaz³

et al. 2011

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T OOb b j je ec c t ti i v ve e: : Pros ta te can cer is a mul ti fac to ri al in he ri ted di se a se af fec ting one in six men in in dus tri al co un tri es. A number of mu ta ti ons in key pro te ins of the cell cycle mac hi nery or sig nal trans duc ti on path ways ha ve already be en as so ci a ted with pros ta te can cer; but re cently, a number of poly morp hisms in pro te ins that func ti on in less po pu lar cel lu lar path ways have been in ves ti ga ted as pos sib le risk fac tors. In this study, we eva lu a ted the ef fects of two ge ne poly morp hisms in enz ymes func ti o ning in dis tinct me ta bo lic path ways on pros ta te can cer sus cep ti bi lity. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : Al le le and ge noty pe as so ci a ti ons of the COMT Val108/158Met and MTHFR C677T ge ne poly morphisms we re stu di ed in a to tal of 112 Tur kish pros ta te can cer pa ti ents who constituted our study group while 145 he althy ma les cons ti tu ted our con trol gro up. Ge no mic DNA was iso la ted from the pe rip he ral blo od le u kocy tes of the sub jects and analy zed by two dif fe rent re al-ti me polymerase chain reaction as says. R Re e s su ul lt ts s: : The fre qu ency of the he te rozy go us COMT G/A and the ho mozy go us MTHFR T/T ge noty pes we re hig her in the study gro up compared to the con trol gro up (47.3% ver sus 34.5%; and 14.3% ver sus 7.6%, res pec ti vely). Pros ta te can cer sub jects with the he te rozy go us MTHFR C/T ge noty pe had hig her prostate specific antigen va lu es. Ne vert he less, no sta tis ti cally sig ni fi cant as soci a ti on was found between the se poly morp hisms alo ne or in com bi na ti on and the risk of de ve lo ping pros ta te can cer. C Co on nc c l lu u s si i o on n: : We sug gest that func ti o nal ge ne poly morp hisms in me ta bo lic pro te ins pre dis po se sub jects to in cre a sed risk of de ve lo ping can cer; but, not as strong as mu ta ti ons in pro toon co ge nes or tu mor-sup pres sor ge nes.K Ke ey y W Wo or rd ds s: : Pros ta tic ne op lasms; pros ta tic ne op lasms; ca tec hol O-methy ltrans fe ra se; meth yle ne tet rahy dro fo la te re duc ta se (NADPH2) Ö ÖZ ZE ET T A Am ma aç ç: : Pros tat kan se ri en düs tri leş miş ül ke ler de her al tı er kek ten bi ri ni et ki le yen mul ti fak tö -ri yel ka lıt sal bir has ta lık tır. Ha li ha zır da hüc re dön gü sü çar kı nın ve ya sin yal ak tar ma yo lak la rı nın anah tar pro te in le rin de ki pek çok mu tas yon pros tat kan se ri ile iliş ki len di ril miş tir; fa kat, son za manlar da da ha az po pü ler hüc re sel yo lak lar da iş lev ya pan pro te in ler de ki pek çok po li mor fizm de ola sı risk fak tör le ri ola rak araş tı rıl mak ta dır. Bu ça lış ma da, pros tat kan se ri ne yat kın lık ya ra ta bi le cek fark lı meta bo lik yo lak lar da yer alan en zim ler de ki iki gen po li mor fiz mi nin et ki le ri ni de ğer len dir dik. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : Ça lış ma gru bu mu zu oluş tu ran top lam 112 Türk...

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“…Homocysteine, an amino acid intermediate in the conversion of methionine to cysteine, has been recognized as a new emerging risk factor for CVD (3). Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in homocysteine metabolism (4), catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for methylation of homocysteine to methionine (5). The MTH-FR gene is located at the end of the short arm of chromosome 1 (1p36.3) (6).…”

Section: Sonuçmentioning

confidence: 99%

Statin and MTHFR C677T Polymorphism in Patients with Cardiovascular Diseases

İzmirli¹,

Bacaksız²,

Alptekin³

et al. 2014

Bezmialem Science

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Objective: Cardiovascular disease (CVD) is the leading cause of death worldwide. The methylenetetrahydrofolate reductase (MTHFR) gene, located on the short (p) arm of chromosome 1 at position 36.3 (1p36.3), might be a possible risk factor for the pharmacogenetics in CVD. A common polymorphism in MTHFR (C677T, Ala→Val) decreases this enzyme activity and increases the homocysteine concentrations, predisposing one to heart disease. Alternatively, statins, cholesterol-reducing agents, are also used to reduce the homocysteine blood concentrations; the aim of the present study was to evaluate how the genotype frequencies of the MTHFR C677T polymorphism, namely rs1801133, change in the cardiovascular system in patients treated with statin. Methods:In this study, the genotype distribution of the MTHFR C677T polymorphism in CVD patients treated with statin (hydrophilic and lipophilic) (n=290) and healthy controls (n=151) was assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results:In this study, a statistically significant difference in genotype frequencies for the MTHFR C677T polymorphism was found between CVD patients treated with statin and controls (p=0.037). Yöntemler: Bu çalışmada, lipofilik ve hidrofilik statinler ile tedavi edilen kardiyovasküler sistem hastalarında (n=290) ve sağlıklı kontrollerde (n=151) MTHFR C677T polimorfizmindeki genotip dağılımları incelenmiştir. Genotipleme, Polimeraz zincir reaksiyonu (PCR) ve restriksiyon parça uzunluk polimorfizm (RFLP) yöntemi ile yapılmıştır. Bulgular: Bu çalışmada, MTHFR C677T polimorfizminin genotip dağılımında statin tedavisi gören kardiyovasküler sistem hastaları ile kontrol grubu arasında istatistiksel olarak anlamlı bir fark gözlenmiştir (p=0,037). ConclusionSonuç: Türk popülasyonunda statin ile tedavi edilen kardiyovasküler sistem hastaları ile MTHFR C677T polimorfizmi arasında istatistiksel olarak anlamlı bir ilişki ilk kez gösterilmiştir.

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Analysis of cell-cycle kinetics and sulfur amino acid metabolism in methionine-dependent tumor cell lines; the effect of homocysteine supplementation

Cited by 22 publications

References 22 publications

Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference

Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference

Effects of the Catechol-O-Methyltransferase Val108/158Met and Methylenetetrahydrofolate Reductase C677T Gene Polymorphisms on Prostate Cancer Susceptibility

Statin and MTHFR C677T Polymorphism in Patients with Cardiovascular Diseases

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