Suppression by L-methionine of cell cycle progression in LNCaP and MCF-7 cells but not benign cells.

Suppression by L-methionine of cell cycle progression in LNCaP and MCF-7 cells but not benign cells.
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DOI:
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发表时间:
2010-06
影响因子:
2
通讯作者:
Maximo A. Benavides;K. Hagen;W. Fang;Pan Du;Simon M. Lin;M. Moyer;Wancai Yang;K. Bland;W. Grizzle;M. Bosland
Maximo A. Benavides;K. Hagen;W. Fang;Pan Du;Simon M. Lin;M. Moyer;Wancai Yang;K. Bland;W. Grizzle;M. Bosland
中科院分区:
医学4区
文献类型:
--
作者:
Maximo A. Benavides;K. Hagen;W. Fang;Pan Du;Simon M. Lin;M. Moyer;Wancai Yang;K. Bland;W. Grizzle;M. Bosland

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背景/目的蛋氨酸抑制乳腺癌和前列腺癌细胞的增殖。本研究旨在探讨蛋氨酸对肿瘤细胞周期的影响及其对肿瘤细胞的选择性。材料和方法使用MCF-7(乳腺)、LNCaP(前列腺)和LS-174(结肠)癌细胞(野生型p53)、DU-145(前列腺)和SW480(结肠)癌细胞(突变p53),以及永生化的非致瘤性MCF-10A(乳腺)、BPH-1(前列腺)和NCM-460(结肠)上皮细胞。流式细胞术检测细胞周期效应,微阵列分析和QRT-PCR检测细胞周期相关基因表达。结果在LNCaP、DU145和MCF-7细胞中,5 mg/ml的l -蛋氨酸作用72小时(非凋亡)阻滞细胞周期,但在未转化的细胞和LS-174细胞中没有阻滞细胞周期。LNCaP和MCF-7细胞在G(1)时阻滞,而DU-145细胞在s(1)时阻滞。蛋氨酸上调CDKIs,下调CDKs。结论l -蛋氨酸可选择性抑制乳腺癌和前列腺癌细胞的增殖,但对非致瘤性细胞无抑制作用,可能具有治疗作用。P53的状态似乎决定了蛋氨酸起作用的细胞周期阶段。
BACKGROUND/AIM Methionine inhibits proliferation of breast and prostate cancer cells. This study aimed to determine cell cycle effects of methionine and selectivity for cancer cells. MATERIALS AND METHODS MCF-7 (breast), LNCaP (prostate), and LS-174 (colon) cancer cells (wild-type p53), DU-145 (prostate) and SW480 (colon) cancer cells (mutated p53), and immortalized, non-tumorigenic MCF-10A (breast), BPH-1 (prostate), and NCM-460 (colon) epithelial cells were used. Cell cycle effects were assessed by flow cytometry and cell cycle-related gene expression by microarray analysis and QRT-PCR. RESULTS L-Methionine at 5 mg/ml for 72 hours (non-apoptotic) arrested cell cycle in LNCaP, DU145, and MCF-7 cells, but not in untransformed cells, nor in LS-174 cells. LNCaP and MCF-7 cells were arrested at G(1), but DU-145 at S. Methionine up-regulated CDKIs and down-regulated CDKs. CONCLUSION L-Methionine selectively inhibits proliferation of breast and prostate cancer cells, but not non-tumorigenic cells, and may thus have therapeutic benefits. p53 status appeared to determine the cell cycle stage at which methionine acts.