Evaluation of photodynamic therapy effects of novel zinc (II) phthalocyanine through a possible interaction with toll-like receptor signaling pathway

In this work, 3-({6-[3-(dimethylamino)phenoxy]hexyl}oxy)phthalonitrile (2) and the target zinc (II) phthalocyanine (3) and its ammonium derivative (3a) are synthesized, and the phototoxic effects of 3a were examined using different methods on A549 lung cancer cells. Then, the toll-like receptor (TLR) signaling pathway was examined to determine the cell death mechanism in the A549 cancer cells. The results showed that 3a did not have noticeable cytotoxic actions on A549 cells at used concentrations. However, the compound markedly reduced the cell viability when irradiated by the red light for 5 and 15 min (LumaCare/LC-122A/LC2020-09-784, Prob: LUM L [700 nm CL] [15 mW cm(-2)]). Additionally, Annexin V/PI staining suggested that the cells were induced apoptosis in the presence of 3a (1 mu M) when irradiated with red light for 15 min. Furthermore, the expression of TLR2, TLR4, and caspase-3 significantly increased and phospho-nuclear factor kappa B/total nuclear factor kappa B decreased compared with that of control group (p < 0.05). These results provide strong evidence that 3a is able to induce A549 cell death in a dose and a red-light irradiation time-dependent manner via apoptosis. Therefore, 3a might be an effective photodynamic therapy candidate for lung cancer treatment.

Automated summary

In this study, compound 3a was synthesized and tested on A549 lung cancer cells. The results showed that 3a significantly reduced cell viability and induced apoptosis when irradiated with red light. The Toll-like receptor signaling pathway and related protein expression were also observed to change. This suggests that 3a can induce A549 cell death in a dose and red-light irradiation time-dependent manner and may be an effective candidate for photodynamic therapy in lung cancer treatment.