Department of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang 524023, PR China.
School of Materials Science and Energy Engineering, Foshan University, Foshan 528000, PR China.
Bioorg Med Chem. 2019 Jun 15;27(12):2598-2608. doi: 10.1016/j.bmc.2019.03.051. Epub 2019 Mar 27.
Water-soluble porphyrins are considered promising drug candidates for photodynamic therapy (PDT). This study investigated the PDT activity of a new water-soluble, anionic porphyrin (1-Zn), which possesses four negative charges. The photodynamic anticancer activity of 1-Zn was investigated by the MTT assay, with mTHPC as a positive control. The cellular distribution was determined by fluorescence microscopy. Holographic and phase contrast images were recorded after 1-Zn treatment with a HoloMonitor™ M3 instrument. The inhibition of A549 cell growth achieved by inducing apoptosis was investigated by flow cytometry and fluorescence microscopy. DNA damage was investigated by the comet assay. The expression of apoptosis-related proteins was also measured by western blot assays. 1-Zn had better phototoxicity against A549 cells than HeLa and HepG2 cancer cells. Interestingly, 1-Zn was clearly located almost entirely in the cell cytoplasmic region/organelles. The late apoptotic population was less than 1.0% at baseline in the untreated and only light-treated cells and increased to 40.5% after 1-Zn treatment and irradiation (P < 0.05). 1-Zn triggered significant ROS generation after irradiation, causing ΔΨm disruption (P < 0.01) and DNA damage. 1-Zn induced A549 cell apoptosis via the mitochondrial apoptosis pathway. In addition, 1-Zn bound in the groove of DNA via an outside binding mode by pi-pi stacking and hydrogen bonding. 1-Zn exhibits good photonuclease activity and might serve as a potential photosensitizer (PS) for lung cancer cells.
水溶性卟啉被认为是光动力疗法 (PDT) 的有前途的药物候选物。本研究研究了一种新的水溶性、阴离子卟啉 (1-Zn) 的 PDT 活性，该卟啉具有四个负电荷。通过 MTT 测定法研究了 1-Zn 的光动力抗癌活性，并以 mTHPC 作为阳性对照。通过荧光显微镜确定细胞分布。使用 HoloMonitor™ M3 仪器在 1-Zn 处理后记录全息和相差图像。通过流式细胞术和荧光显微镜研究通过诱导细胞凋亡抑制 A549 细胞生长。通过彗星试验研究 DNA 损伤。还通过 Western blot 测定法测量了凋亡相关蛋白的表达。1-Zn 对 A549 细胞的光毒性优于 HeLa 和 HepG2 癌细胞。有趣的是，1-Zn 几乎完全位于细胞质区域/细胞器中。在未处理和仅光照处理的细胞中，基线时晚期凋亡细胞群小于 1.0%，而在用 1-Zn 处理和照射后增加到 40.5%（P<0.05）。1-Zn 在照射后引发明显的 ROS 生成，导致 ΔΨm 破坏（P<0.01）和 DNA 损伤。1-Zn 通过线粒体凋亡途径诱导 A549 细胞凋亡。此外，1-Zn 通过 π-π 堆积和氢键以外部结合模式结合到 DNA 的沟槽中。1-Zn 表现出良好的光解酶活性，可能作为肺癌细胞的潜在光敏剂 (PS)。
