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Effects of Methylation Inhibition on Cell Prolieration and Metastasis of Human Breast Cancer Cells

机译:甲基化抑制对人乳腺癌细胞细胞增殖和转移的影响

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Breast cancer is the second most fatal cancer in women. Adenosine has been shownto induce apoptosis through various mechanisms including adenosine receptor activation,adenosine monophosphate (AMP) conversion, AMP-activated protein kinase activation, orconversion to S-adenosylhomocysteine, which is an inhibitor of S-adenosylmethionine-dependent methyltransferases. Since the pathways involved in the anticancer activity ofadenosine analogues are not still clearly understood, I examined the relationship between me-thyltransferase inhibition and the anticancer, antimetastatic effect of adenosine dialdehyde(AdOx) which is known for AdoHcy hydrolase inhibitor, which result in methylation inhibi-tion, using non-invasive and invasive human breast cancer cells (HBCs MCF-7 and MDA-MB231, respectively). Morphological changes and condensed chromatin were observed in HBCstreated with AdOx. Cytotoxicity was increased and DNA synthesis and cell counts were de-creased by AdOx in HBCs, but the cytotoxicity was higher in MCF-7 than in MDA-MB 231. InMDA-MB 231, AdOx lowered the expression of G1/S regulators and the tumor suppressorp21WAF1/Cip 1 . In MCF-7, apoptotic molecules and tumor suppressor p21WAF1/Cip 1 expres-sion were induced by AdOx. Colony dispersion and cell migration was inhibited by AdOx andthe activities of matrix metalloproteinase-2 /-9, which are key enzymes for cancer invasion andmigration, were decreased by AdOx. But, the mRNA levels of MMP-2 and MMP-9 were notaffected in accordance with the changes in enzymatic activity. Mammary-specific serine prote-ase inhibitor was increased by AdOx in both cell lines. These results suggest that methyltrans-ferase inhibition by AdOx may decrease cell viability and influence cell cycle distribution andmigratory potential, providing evidence of methylation inhibition as a potential target for anti-cancer and antimetastatic effects in HBCs.
机译:乳腺癌是女性中最致命的癌症。已经显示腺苷通过各种机制诱导细胞凋亡,包括腺苷受体活化,腺苷一磷酸盐(AMP)转化,amp-活化的蛋白激酶活化,and转化为S-腺瘤肌细胞,这是依赖于S-腺苷依赖性甲基转移酶的抑制剂。由于仍然清楚地清楚地清楚地清楚地清楚地清楚地涉及抗癌活性的途径,因此我研究了Me-甲基转移酶抑制与抗癌的关系,腺苷样品酶抑制剂已知的腺苷二丁基(Adox)的抗常用作用,这导致甲基化抑制剂 - 使用非侵入性和侵入性人乳腺癌细胞(分别为HBCS MCF-7和MDA-MB231)。用Adox在Hbcstreat中观察到形态学变化和浓缩染色质。细胞毒性增加,DNA的合成和细胞计数通过ADOX在高负担国家去折痕,但细胞毒性在MCF-7高于在MDA-MB 231的I NMDA-MB 231,ADOX降低G1的表达/ S调节器和所述肿瘤抑制作用P21WAF1 / CIP 1。在MCF-7中,Adox诱导凋亡分子和肿瘤抑制剂P21WAF1 / CIP 1表现出1 expres-sion。 Adox抑制了菌落分散和细胞迁移,并且基质金属蛋白酶-2 / -9的活性是癌症侵袭和迁移的关键酶。但是,根据酶活性的变化,MMP-2和MMP-9的mRNA水平不影响。在两种细胞系中,Adox增加了乳腺特异性丝氨酸蛋白酶抑制剂。这些结果表明,Adox的甲基转移抑制可能降低细胞活力并影响细胞周期分布和潜力潜力,提供甲基化抑制作为抗癌和HBC中抗抗常用作用的靶标的证据。

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