The photoactivatable Ru (II) complex 1 [Ru(bipy)2(dpphen)]Cl2 (where bipy = 2,2′-bipyridine and dpphen = 2,9-diphenyl-1,10-phenanthroline) has been shown to possess promising anticancer activity against triple negative adenocarcinoma MDA-MB-231 cells. The present study aims to elucidate the plausible mechanism of action of the photoactivatable complex 1 against MDA-MB-231 cells. Upon photoactivation, complex 1 exhibited time-dependent cytotoxic activity with a phototoxicity index (PI) of >100 after 72 h. A significant increase in cell rounding and detachment, loss of membrane integrity, ROS accumulation and DNA damage was observed. Flow cytometry and a fluorescent apoptosis/necrosis assay showed an induction of cell apoptosis. Western blot analysis revealed the induction of intrinsic and extrinsic pathways and inhibition of the MAPK and PI3K pathways. The photoproduct of complex 1 showed similar effects on key apoptotic protein expression confirming that it is behind the observed cell death. In conclusion, the present study revealed that complex 1 is a potent multi-mechanistic photoactivatable chemotherapeutic drug that may serve as a potential lead molecule for targeted cancer chemotherapy.

已证明可光活化的Ru（II）配合物1 [Ru（bipy）2（dpphen）] Cl2（其中bipy = 2,2'-联吡啶，dpphen = 2,9-二苯基-1,10-菲咯啉）具有广阔的前景抗三阴性腺癌MDA-MB-231细胞的抗癌活性。本研究旨在阐明光活化复合物1对抗MDA-MB-231细胞的合理作用机理。光活化后，复合物1表现出随时间变化的细胞毒性活性，72小时后光毒性指数（PI）> 100。观察到细胞圆形和脱离，膜完整性丧失，ROS积累和DNA损伤显着增加。流式细胞仪和荧光细胞凋亡/坏死分析表明诱导细胞凋亡。蛋白质印迹分析揭示了内在和外在途径的诱导以及对MAPK和PI3K途径的抑制。配合物1的光产物对关键的凋亡蛋白表达显示出相似的作用，从而证实其在观察到的细胞死亡之后。总之，本研究表明，复杂1 是一种有效的多机制光激活化学疗法药物，可作为靶向癌症化疗的潜在先导分子。