Archives of oral biology · 2026
Azoxystrobin induces mitochondrial apoptosis by inhibiting cytochrome b Qo site of mitochondrial complex Ⅲ in oral leukoplakia cells and a mouse model.
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Li Lingyu, Lu Yunping, Shen Yajun, Wang Wenchao, Yang Jing, Wang Min, Miao Congcong, Zhang Min, Tang Xiaofei
Аннотация
OBJECTIVE: Oral leukoplakia (OLK) is an oral potentially malignant disorder with the potential to transform into oral squamous cell carcinoma. Our previous study demonstrated that azoxystrobin (AZOX), a natural product, reduced malignant transformation in a mouse model. Building on these findings, the present study aims to investigate the molecular mechanisms underlying AZOX-induced mitochondrial apoptosis in OLK.
DESIGN: In vitro, mitochondrial complex III activity and adenosine triphosphate generation were assessed using a microplate reader. Mitochondrial reactive oxygen species levels were detected by flow cytometry and fluorescence microscopy, whereas mitochondrial membrane potential was evaluated using JC-1 staining. The apoptosis rate was quantified by flow cytometry. In tongue OLK tissues obtained from the animal model, the expression of mitochondrial apoptosis-related markers was examined by immunohistochemistry. In dysplastic oral keratinocyte cells, the expression of mitochondrial apoptosis-related markers was investigated by quantitative real-time polymerase chain reaction and western blot. In addition, the binding of AZOX to cytochrome b (Cyt b) was verified using cellular thermal shift assay.
RESULTS: AZOX induced mitochondrial dysfunction and modulated the expression of mitochondrial apoptosis-related markers in both in vivo and in vitro models. Mechanistically, AZOX triggered mitochondrial apoptosis by inhibiting the Qo site of Cyt b in mitochondrial complex III. Direct binding of AZOX to Cyt b was further confirmed.
CONCLUSION: AZOX induces mitochondrial dysfunction and apoptosis by targeting the Cyt b Qo site of mitochondrial complex III in OLK, thereby providing a mechanistic basis for its potential therapeutic application.
DESIGN: In vitro, mitochondrial complex III activity and adenosine triphosphate generation were assessed using a microplate reader. Mitochondrial reactive oxygen species levels were detected by flow cytometry and fluorescence microscopy, whereas mitochondrial membrane potential was evaluated using JC-1 staining. The apoptosis rate was quantified by flow cytometry. In tongue OLK tissues obtained from the animal model, the expression of mitochondrial apoptosis-related markers was examined by immunohistochemistry. In dysplastic oral keratinocyte cells, the expression of mitochondrial apoptosis-related markers was investigated by quantitative real-time polymerase chain reaction and western blot. In addition, the binding of AZOX to cytochrome b (Cyt b) was verified using cellular thermal shift assay.
RESULTS: AZOX induced mitochondrial dysfunction and modulated the expression of mitochondrial apoptosis-related markers in both in vivo and in vitro models. Mechanistically, AZOX triggered mitochondrial apoptosis by inhibiting the Qo site of Cyt b in mitochondrial complex III. Direct binding of AZOX to Cyt b was further confirmed.
CONCLUSION: AZOX induces mitochondrial dysfunction and apoptosis by targeting the Cyt b Qo site of mitochondrial complex III in OLK, thereby providing a mechanistic basis for its potential therapeutic application.