Photo-Induced Cytotoxicity and Anti-Metastatic Activity of Ruthenium(II)-Polypyridyl Complexes Functionalized with Tyrosine or Tryptophan
The synergistic effect of oxygen, light, and photosensitizer (PS) has found applications in medicine for the treatment of cancer through photodynamic therapy (PDT). Induction of apoptosis to cancerous cells will prevent tumor metastasis that spreads cancer cells to the neighboring organs/tissues. Herein, we report the two apoptotic Ru(II)-polypyridyl complexes that are functionalized with pendent amino acid moieties tyrosine (1) and tryptophan (2), respectively. These two water soluble complexes were found to interact strongly (Ka1 = (1.18 ± 0.28)105 M-1 and Ka2 = (1.57 ± 0.77)105 M-1) with CT-DNA. Isothermal titration calorimetry (ITC) studies revealed that these complexes bind to CT-DNA through an entropically driven process. Both the complexes showed photo-induced cytotoxicity and exhibits apoptotic activity under photo-irradiation conditions. The comet assay indicated that these complexes can damage cellular DNA, which was attributed to the significant buildup of 1O2 level even on irradiation with low intensity light (10 J/cm2, λRange 450 - 480 nm). This photoinduced DNA damage and apoptosis in A549 cells were induced by reactive oxygen species (ROS) and occurred through up-regulation of apoptotic marker caspase-3. Control experiments under the dark condition revealed an insignificant cytotoxicity towards these cells for two photosensitive molecules.