Hydroxy-corrole and its gallium(III) complex as new photosensitizer for photodynamic therapy against breast carcinoma

• Published in: European journal of medicinal chemistry Vol. 208; p. 112794
• Main Authors: Sun, Yan-Mei, Jiang, Xiao, Liu, Ze-Yu, Liu, Ling-Gui, Liao, Yu-Hui, Zeng, Lei, Ye, Yong, Liu, Hai-Yang
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 15.12.2020
• Subjects: Breast carcinoma; Corrole; Gallium(III) complex; Photodynamic therapy; Photosensitizer; Breast carcinoma; Photodynamic therapy; Corrole; Gallium(III) complex; Photosensitizer
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2020.112794

Three mono-hydroxy corroles 1–3 and their gallium(III) complexes Ga1-3 were synthesized, and their photodynamic antitumour activities towards breast cancer cells were investigated. All corroles showed excellent cytotoxicity against the MDA-MB-231 and 4T1 cell lines upon light irradiation at 625 nm. Ga3 exhibited excellent phototoxicity and selectivity against MDA-MB-231 cells, with an IC50 of 0.06 ± 0.03 μM and a selective index value of 1338.83 (relative to human normal Huvec cells). The performance of Ga3 was even better than that of the clinical photodynamic therapy drug m-THPC. A preliminary mechanistic investigation revealed that corrole 3 and Ga3 were mainly located in the cytoplasm. Upon irradiation, they could generate intracellular reactive oxygen to destroy the mitochondrial membrane potential and arrest the cell cycle at the sub-G1 phase. Flow cytometry revealed that corrole 3 and Ga3 induced cancer cell apoptosis after photodynamic treatment. Corrole 3 and Ga3 displayed negligible cytotoxicity in the dark. These results suggest that corrole 3 and Ga3 are promising candidates for use in the photodynamic therapy of breast cancer. Hydroxy-corrole and its gallium(III) complex induced breast cancer cells apoptosis with red light irradiation. [Display omitted] •The photophysical and photochemical properties of hydroxy-corroles were studied.•Corrole 3 and Ga3 exhibited excellent PDT efficacy against breast cancer cells.•Corrole 3 and Ga3 induced breast cancer cells apoptosis upon 625 nm LED irradiation.