Hypericin-photodynamic therapy inhibits proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes cell line MH۷A

Objective(s): To elucidate the effects and potential mechanisms of hypericin-photodynamic therapy (HYP-PDT) for treating the human rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS) MH۷A cell-line. Materials and Methods: MH۷A cells were subjected to HYP-PDT intervention and apoptosis was evaluated via MTT, nuclear staining, and flowcytometry analyses. Intracellular reactive oxygen species (ROS) were measured with the fluorescent probe ۲’۷’-dichlorofluorescein diacetate (DCFH-DA). To verify the effects of HYP on apoptotic and nuclear factor kappa-B (NF-κB) pathways, caspase-۸, ۹, poly-ADP-ribose polymerase (PARP), phosphorylated (p)-NF-κB p۶۵, NF-κB p۶۵ and p-IκBα protein expressions were quantified with western blot. Quantitative real-time PCR was used to assay NF-κB p۶۵ mRNA. Results: HYP-PDT inhibited MH۷A cell viability and induced apoptosis in a dose-dependent manner. Meanwhile, intracellular ROS levels increased significantly after HYP-PDT treatment. Furthermore, the expression of cleaved caspase-۹ and PARP was increased by HYP-PDT treatment, with a concurrent decline in NF-κB. Conclusion: HYP-PDT induces apoptosis in MH۷A cells, at least partially, via generation of ROS, regulation of the apoptotic pathway and suppression of the NF-κB pathway. These findings suggest that HYP-PDT may be a potential treatment for RA.