The manganese(III) porphyrin MnTnHex-2-PyP(5+) modulates intracellular ROS and breast cancer cell migration: Impact on doxorubicin-treated cells.

The manganese(III) porphyrin MnTnHex-2-PyP(5+) modulates intracellular ROS and breast cancer cell migration: Impact on doxorubicin-treated cells.
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锰(III)卟啉MNTNHEX-2-PYP(5+)调节细胞内ROS和乳腺癌细胞迁移:对阿霉素治疗的细胞的影响。

DOI:
10.1016/j.redox.2018.10.016
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发表时间:
2019-01
期刊:
影响因子:
11.4
通讯作者:
Fernandes AS
Fernandes AS
中科院分区:
生物学1区
文献类型:
--
作者:
Flórido A;Saraiva N;Cerqueira S;Almeida N;Parsons M;Batinic-Haberle I;Miranda JP;Costa JG;Carrara G;Castro M;Oliveira NG;Fernandes AS

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锰(III)卟啉(MNP)是超氧化物歧化酶(SOD)模拟物,在与化疗和放疗方案组合的癌症治疗中具有已证明的有益效果。尽管正在进行临床试验,但对MNP对转移的影响知之甚少,因此了解MNP如何影响这一过程至关重要。在本工作中,在乳腺癌细胞(MCF-7和MDA-MB-231)中单独或与多柔比星(dox)组合评估了MnP MnTnHex-2-PyP 5+在转移相关过程中的影响。用非细胞毒性浓度的MnP和Dox共处理细胞改变了细胞内ROS,增加了H2 O2。虽然单独的MnP没有改变细胞迁移,但共同暴露导致集体细胞迁移和趋化性降低。此外,MNP减少了Dox诱导的MDA-MB-231细胞随机迁移的增加。用MnP或dox处理降低了MDA-MB-231细胞的蛋白水解侵袭,尽管在与两种化合物共暴露后效果更明显。此外,为了探索所观察到的效应的细胞机制,还研究了细胞粘附、扩散、粘着斑和NF-κB活化。尽管根据分析的终点观察到不同的作用,但总体而言,在dox处理的细胞中由MnP诱导的改变与治疗上有利的结果一致。MnPs是SOD模拟物,在癌症中具有潜在的治疗应用。评估了MNP对乳腺癌转移相关过程的影响。用MnP+dox处理减少集体细胞迁移、趋化和侵袭。MNP还减少了阿霉素诱导的MDA-MB-231细胞随机迁移的增加。MNP与dox的组合显示了治疗有利的效果。
Manganese(III) porphyrins (MnPs) are superoxide dismutase (SOD) mimics with demonstrated beneficial effects in cancer treatment in combination with chemo- and radiotherapy regimens. Despite the ongoing clinical trials, little is known about the effect of MnPs on metastasis, being therefore essential to understand how MnPs affect this process. In the present work, the impact of the MnP MnTnHex-2-PyP5+ in metastasis-related processes was assessed in breast cancer cells (MCF-7 and MDA-MB-231), alone or in combination with doxorubicin (dox). The co-treatment of cells with non-cytotoxic concentrations of MnP and dox altered intracellular ROS, increasing H2O2. While MnP alone did not modify cell migration, the co-exposure led to a reduction in collective cell migration and chemotaxis. In addition, the MnP reduced the dox-induced increase in random migration of MDA-MB-231 cells. Treatment with either MnP or dox decreased the proteolytic invasion of MDA-MB-231 cells, although the effect was more pronounced upon co-exposure with both compounds. Moreover, to explore the cellular mechanisms underlying the observed effects, cell adhesion, spreading, focal adhesions, and NF-κB activation were also studied. Although differential effects were observed according to the endpoints analysed, overall, the alterations induced by MnP in dox-treated cells were consistent with a therapeutically favorable outcome. MnPs are SOD mimics with potential therapeutic applications in cancer. The impact of an MnP on breast cancer metastasis-related processes was assessed. Treatment with MnP+dox decreased collective cell migration, chemotaxis and invasion. MnP also reduced the dox-induced increase in random migration of MDA-MB-231 cells. Combination of MnP with dox revealed therapeutically favorable effects.
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