Osaki Tomohiro, Sakata Isao, Uto Yoshihiro, Azuma Kazuo, Murahata Yusuke, Tsuka Takeshi, Itoh Norihiko, Imagawa Tomohiro, Okamoto Yoshiharu
Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori, Japan
Porphyrin Laboratory, Okayama, Japan.
Anticancer Res. 2017 Apr;37(4):1723-1728. doi: 10.21873/anticanres.11504.
The lipophilic photosensitizer, TONS 501, is a novel porphyrin-derived methyl ester that was developed for photodynamic antimicrobial chemotherapy. This study developed a hydrophilic and anionic porphyrin salt of this compound (TONS 501-Na) for use in photodynamic therapy (PDT). This chlorin derivative is synthesized from the protoporphyrin IX dimethyl ester.
We investigated the in vitro cytotoxic effects of TONS 501-Na-mediated PDT on EMT6 mouse breast cancer cells. EMT6 cells were incubated with 0-100 μg/ml TONS 501-Na for 24 h prior to replacing the culture medium and exposing the cells to 6 mW/cm diode laser irradiation at 0-13 J/cm to induce PDT. Morphological changes and cell viability were evaluated 24 h after PDT. The percentages of apoptotic cells were evaluated 4 h and 24 h after PDT.
The concentrations of TONS 501-Na that killed 50% of EMT6 cells after exposure to light doses of 0, 0.4, 3, 6, or 13 J/cm were 84.6, 33.2, 18, 8.2, and 2.2 μg/ml, respectively. Tumor cells exposed to PDT showed chromatin condensation and fragmentation. The percentages of apoptotic cells increased in a TONS 501-Na concentration-dependent manner in the PDT group, and were significantly higher than those in the control group or in cells treated with TONS 501-Na or laser irradiation alone.
TONS 501-Na-mediated PDT induced mouse breast cancer cell death in a concentration-dependent manner. Future studies should evaluate the in vivo pharmacokinetics, tissue distribution, and photodynamic effects of TONS 501-Na.
亲脂性光敏剂TONS 501是一种新型卟啉衍生的甲酯，用于光动力抗菌化疗。本研究开发了该化合物的一种亲水性阴离子卟啉盐（TONS 501-Na）用于光动力疗法（PDT）。这种二氢卟吩衍生物由原卟啉IX二甲酯合成。
我们研究了TONS 501-Na介导的PDT对EMT6小鼠乳腺癌细胞的体外细胞毒性作用。在更换培养基并将细胞暴露于0-13 J/cm²的6 mW/cm²二极管激光照射以诱导PDT之前，将EMT6细胞与0-100 μg/ml的TONS 501-Na孵育24小时。在PDT后24小时评估形态变化和细胞活力。在PDT后4小时和24小时评估凋亡细胞的百分比。
在暴露于0、0.4、3、6或13 J/cm²光剂量后杀死50%EMT6细胞的TONS 501-Na浓度分别为84.6、33.2、18、8.2和2.2 μg/ml。暴露于PDT的肿瘤细胞显示染色质浓缩和碎片化。在PDT组中，凋亡细胞的百分比以TONS 501-Na浓度依赖性方式增加，并且显著高于对照组或仅用TONS 501-Na或激光照射处理的细胞。
TONS 501-Na介导的PDT以浓度依赖性方式诱导小鼠乳腺癌细胞死亡。未来的研究应评估TONS 501-Na的体内药代动力学、组织分布和光动力效应。
