Piroctone olamine disrupts mitochondrial dynamics in glioma cells through the PI3K/AKT pathway / 南方医科大学学报

OBJECTIVE@#To investigate the growth-inhibitory and pro-apoptotic effects of piroctone olamine (PO) on glioma cells and explore the underlying mechanism.@*METHODS@#Human glioma cell lines U251 and U373 were treated with PO and the changes in cell proliferation were detected using CCK-8 assay and EdU assay. Clone formation assay and flow cytometry were used to examine the changes in clone formation ability and apoptosis of the treated cells. Mitochondrial membrane potential of the cells and morphological changes of the mitochondria were detected using JC-1 staining and a fluorescence probe, respectively. The expressions of mitochondrial fission protein DRP1 and the fusion protein OPA1 were determined with Western blotting. Transcriptome sequencing and differential gene enrichment analysis was performed, and the expression levels of PI3K, AKT and p-AKT in the treated cells were verified using Western blotting.@*RESULTS@#CCK-8 assay showed that PO significantly inhibited the proliferation of U251 and U373 cells in a time- and dose-dependent manner (P < 0.001). EdU test showed that the proliferative activity of PO-treated cells was significantly decreased, and the number of cell colonies also decreased significantly (P < 0.01). PO treatment significantly increased apoptotic rates (P < 0.01), decreased mitochondrial membrane potential and caused obvious changes in mitochondrial morphology of the cells. Pathway enrichment analysis showed that the down-regulated genes were significantly enriched in the PI3K/AKT pathway, which was verified by Western blotting showing significantly down-regulated expression levels of PI3K, AKT and p-AKT in PO-treated cells (P < 0.05).@*CONCLUSION@#PO interferes with mitochondrial fusion and fission function through the PI3K/AKT pathway, thereby inhibiting the proliferation and increasing apoptosis of glioma cells.

Efficacy and Safety of Cream Containing Climbazole/Piroctone Olamine for Facial Seborrheic Dermatitis: A Single-Center, Open-Label Split-Face Clinical Study

BACKGROUND: Seborrheic dermatitis (SD) is a multifactorial disease; Malassezia species play an important role in its pathogenesis. OBJECTIVE: We aimed to determine whether a cream containing climbazole/piroctone olamine (C/P cream), antifungal agents with expected efficacy against Malassezia species, could improve SD symptoms. METHODS: We instructed 24 patients with mild-to-moderate SD to apply the C/P cream and emollient cream on the right and left sides of the face, respectively, every morning and evening for 4 weeks. The casual sebum level (measured with Sebumeter®; Courage & Khazaka Electronic GmbH, Germany) and the extent of erythema (measured with Mexameter®; Courage & Khazaka Electronic GmbH) on the face were measured at baseline and after 4 weeks. The minimal inhibitory concentration (MIC) was determined to demonstrate the antifungal activity of the C/P cream. RESULTS: The casual sebum level and erythema were measured at week 4, and the median values demonstrated a quantitative improvement on the C/P cream-treated right side of the face compared to the emollient cream-treated left side. For the C/P cream, the MICs were 0.625, 5, 0.625, and 2.5 mg/ml for Malassezia restricta, M. globosa, M. sympodialis, and M. slooffiae, respectively. CONCLUSION: Based on the reduced casual sebum level and extent of erythema, the antifungal activity of C/P cream against Malassezia species seems useful for the treatment of mild to moderate SD.