Department of Chemistry, Faculty of Exact Sciences, and the, Institute for Nanotechnology and advanced materials (BINA), Bar-Ilan University, 5290002, Ramat-Gan, Israel.
ChemistryOpen. 2021 Apr;10(4):486-492. doi: 10.1002/open.202100044.
The Cu(II)-diacetyl-bis (N4-methylthiosemicarbazone) complex (ATSM-Cu(II)) has been suggested as a promising positron emission tomography (PET) agent for hypoxia imaging. Several in-vivo studies have shown its potential to detect hypoxic tumors. However, its uptake mechanism and its specificity to various cancer cell lines have been less studied. Herein, we tested ATSM-Cu(II) toxicity, uptake, and reduction, using four different cell types: (1) mouse breast cancer cells (DA-3), (2) human embryonic kidney cells (HEK-293), (3) breast cancer cells (MCF-7), and (4) cervical cancer cells (Hela) under normoxic and hypoxic conditions. We showed that ATSM-Cu(II) is toxic to breast cancer cells under normoxic and hypoxic conditions; however, it is not toxic to normal HEK-293 non-cancer cells. We showed that the Cu(I) content in breast cancer cell after treatment with ATSM-Cu(II) under hypoxic conditions is higher than in normal cells, despite that the uptake of ATSM-Cu(II) is a bit higher in normal cells than in breast cancer cells. This study suggests that the redox potential of ATSM-Cu(II) is higher in breast cancer cells than in normal cells; thus, its toxicity to cancer cells is increased.
Cu(II)-二乙酰基双（N4-甲基硫代半缩酮）配合物（ATSM-Cu(II)）被认为是一种很有前途的用于缺氧成像的正电子发射断层扫描（PET）试剂。几项体内研究表明，它具有检测缺氧肿瘤的潜力。然而，其摄取机制及其对各种癌细胞系的特异性研究较少。在此，我们使用四种不同的细胞类型（1）小鼠乳腺癌细胞（DA-3），（2）人胚肾细胞（HEK-293），（3）乳腺癌细胞（MCF-7）和（4）宫颈癌细胞（Hela）在常氧和缺氧条件下，测试了 ATSM-Cu(II)的毒性、摄取和还原。结果表明，ATSM-Cu(II)在常氧和缺氧条件下对乳腺癌细胞均有毒性；然而，它对正常的非癌细胞 HEK-293 没有毒性。我们发现，在缺氧条件下用 ATSM-Cu(II)处理后，乳腺癌细胞中的 Cu(I)含量高于正常细胞，尽管正常细胞对 ATSM-Cu(II)的摄取比乳腺癌细胞略高。这项研究表明，ATSM-Cu(II)在乳腺癌细胞中的氧化还原电位高于正常细胞，因此其对癌细胞的毒性增加。
