Assessment of the PARP inhibitor talazoparib photosafety profile

• Published in: Biomedicine & pharmacotherapy Vol. 167; p. 115593
• Main Authors: Mateos-Pujante, Alejandro, Jiménez, M. Consuelo, Andreu, Inmaculada
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01-11-2023; Elsevier
• Subjects: Comet assay; Fluorescence microscopy; Photoproduct; Phototoxicity; Protein photooxidation; Reactive oxygen species; Phototoxicity; Reactive oxygen species; Photoproduct; Protein photooxidation; Comet assay; Fluorescence microscopy
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.115593

Talazoparib (TLZ) is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor employed for the treatment of breast cancer. This drug displays an absorption band in the UVA region, and therefore investigation of the possible phototoxic side-effects associated to its administration results of enormous relevance. In this context, we describe here a photochemical and photobiological study to ascertain the photosafety profile of TLZ. Concerning transient species, the singlet and triplet excited states of TLZ were detected by fluorescence (λmax em = 440 nm) and laser flash photolysis experiments (λmax abs = 400 nm), respectively. Remarkably, TLZ irradiation with UVA light in aqueous solution resulted in formation of a stable photooxidated product, TLZ-P, whose absorption band is extended until the visible region. From in vitro experiments, phototoxicity was revealed for the parent drug by neutral red uptake (NRU) assays, with a PIF value of ca 7; besides, TLZ induced formation of reactive oxygen species (ROS) and produced significant damage to both proteins and DNA. By contrast, the singlet and triplet excited states of TLZ-P were not detected, and no photodamage was observed in the NRU experiments. Overall, the results indicate that TLZ induces phototoxicity, whereas its photoproduct exhibits photosafety.
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•Upon UVA irradiation, talazoparib leads to a non-reactive photoproduct.•Neutral red uptake assay of talazoparib reveals that the drug is phototoxic.•Talazoparib induces protein photooxidation.•Reactive oxygen species within cells are detected by fluorescence microscopy.•Non-reversible photodamage to cellular DNA is confirmed by comet assay.