新型哌嗪取代硅酞菁对乳腺癌细胞具有抗癌作用。
Novel piperazine-substituted silicon phthalocyanines exert anti-cancer effects against breast cancer cells.
机构信息
Department of Medical Biology, Institute of Health Sciences, Karadeniz Technical University, Trabzon, Turkey.
Department of Chemistry, Faculty of Sciences, Karadeniz Technical University, Trabzon, Turkey.
出版信息
Photodiagnosis Photodyn Ther. 2022 Mar;37:102734. doi: 10.1016/j.pdpdt.2022.102734. Epub 2022 Jan 20.
BACKGROUND
Photodynamic therapy (PDT) is one of the effective methods that can be used in cancer treatment. In this study, we aimed to investigate the PDT-mediated anti-cancer effects of newly synthesized piperazine-substituted silicon phthalocyanine molecules on breast cancer cells.
METHODS
The compounds were analyzed by different spectroscopic techniques (FT-IR, UV-vis, H NMR, C NMR, MS) and the absorbance characteristics were determined. The cytotoxic effects of silicon phthalocyanines on MDA-MB-231 breast cancer cells and non-tumorigenic MCF-10A cells were evaluated using MTT assay. Detection of apoptotic populations was performed by Annexin V/7AAD assay. HDCFDA dye was used to analyze intracellular reactive oxygen species. The clonogenic activity and cellular motility were analyzed by colony formation assay and in vitro scratch assay, respectively. Caspase-3, PARP1, and cleaved-PARP1 protein levels were analyzed by western blot studies.
RESULTS
Piperazine-substituted silicon phthalocyanines caused high levels of cytotoxic effects and apoptotic cell population in MDA-MB-231 cells, while low levels of cytotoxic effects were observed in MCF-10A cells. Following PDT, intense ROS formation was detected in MDA-MB-231 cells. Colony-forming capacity and cellular motility of MDA-MB-231 cells were highly restricted following PDT, whereas these effects were observed at lower levels in MCF-10A cells. Silicon phthalocyanines caused different effects on cleaved-PARP1 expressions of MDA-MB-231 and MCF-10A cells.
CONCLUSION
These results suggest that piperazine-substituted silicon phthalocyanines can exert selective anti-cancer effects on breast cancer cells and activate cellular death through different molecular pathways. Hence, we believe that they may be used as effective photosensitizer agents in the future.
背景
光动力疗法（PDT）是癌症治疗中一种有效的方法。在这项研究中，我们旨在研究新合成的哌嗪取代硅酞菁分子对乳腺癌细胞的 PDT 介导的抗癌作用。
方法
通过不同的光谱技术（FT-IR、UV-vis、H NMR、C NMR、MS）对化合物进行分析，并确定其吸收特性。通过 MTT 测定法评估硅酞菁对 MDA-MB-231 乳腺癌细胞和非致瘤 MCF-10A 细胞的细胞毒性作用。通过 Annexin V/7AAD 测定法检测凋亡群体。使用 HDCFDA 染料分析细胞内活性氧。通过集落形成测定法和体外划痕测定法分别分析克隆形成活性和细胞迁移。通过 Western blot 研究分析 caspase-3、PARP1 和 cleaved-PARP1 蛋白水平。
结果
哌嗪取代的硅酞菁在 MDA-MB-231 细胞中引起高水平的细胞毒性作用和凋亡细胞群体，而在 MCF-10A 细胞中观察到低水平的细胞毒性作用。PDT 后，在 MDA-MB-231 细胞中检测到强烈的 ROS 形成。PDT 后，MDA-MB-231 细胞的集落形成能力和细胞迁移受到高度限制，而在 MCF-10A 细胞中观察到较低水平的这些效应。硅酞菁对 MDA-MB-231 和 MCF-10A 细胞的 cleaved-PARP1 表达产生不同的影响。
结论
这些结果表明，哌嗪取代的硅酞菁可以对乳腺癌细胞发挥选择性抗癌作用，并通过不同的分子途径激活细胞死亡。因此，我们相信它们将来可能被用作有效的光敏剂。
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