铁螯合剂ATA和DFO对MCF-7乳腺癌细胞及磷酸酶PTP1B和SHP2的抑制活性
Inhibitory Activity of Iron Chelators ATA and DFO on MCF-7 Breast Cancer Cells and Phosphatases PTP1B and SHP2.
作者信息
Kuban-Jankowska Alicja, Sahu Kamlesh K, Gorska-Ponikowska Magdalena, Tuszynski Jack A, Wozniak Michal
机构信息
Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
出版信息
Anticancer Res. 2017 Sep;37(9):4799-4806. doi: 10.21873/anticanres.11886.
BACKGROUND
Rapidly-dividing cancer cells have higher requirement for iron compared to non-transformed cells, making iron chelating a potential anticancer strategy. In the present study we compared the anticancer activity of uncommon iron chelator aurintricarboxylic acid (ATA) with the known deferoxamine (DFO).
MATERIALS AND METHODS
We investigated the impact of ATA and DFO on the viability and proliferation of MCF-7 cancer cells. Moreover we performed enzymatic activity assays and computational analysis of the ATA and DFO effects on pro-oncogenic phosphatases PTP1B and SHP2.
RESULTS
ATA and DFO decrease the viability and proliferation of breast cancer cells, but only ATA considerably reduces the activity of PTP1B and SHP2 phosphatases. Our studies indicated that ATA strongly inactivates and binds in the PTP1B and SHP2 active site, interacting with arginine residue essential for enzyme activity.
CONCLUSION
We confirmed that iron chelating can be considered as a potential strategy for the adjunctive treatment of breast cancer.
背景
与未转化的细胞相比，快速分裂的癌细胞对铁的需求更高，这使得铁螯合成为一种潜在的抗癌策略。在本研究中，我们比较了不常见的铁螯合剂金精三羧酸（ATA）与已知的去铁胺（DFO）的抗癌活性。
材料与方法
我们研究了ATA和DFO对MCF-7癌细胞活力和增殖的影响。此外，我们还对ATA和DFO对促癌磷酸酶PTP1B和SHP2的作用进行了酶活性测定和计算分析。
结果
ATA和DFO均可降低乳腺癌细胞的活力和增殖，但只有ATA能显著降低PTP1B和SHP2磷酸酶的活性。我们的研究表明，ATA能强烈地使PTP1B和SHP2失活并结合在其活性位点，与酶活性所必需的精氨酸残基相互作用。
结论
我们证实铁螯合可被视为乳腺癌辅助治疗的一种潜在策略。
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