S100A8 Induces Cyclophosphamide-Induced Alopecia via NCF2/NOX2-Mediated Ferroptosis

February 2025 in “ Free Radical Biology and Medicine ”

Wenping Xu, Yujie Li, Sheng Wan, Beilei Zhang, Dongfan Wei, Hongyan Zhang, Xiangshu Jin, Bo Xie, Cuiping Guan, Xiuzu Song

S100A8 cyclophosphamide alopecia ferroptosis outer root sheath keratinocytes NCF2 NOX2 hair follicle paquinimod oxidative stress chemotherapy-induced alopecia CYP ORSKs CIA PAQ

Studysummary In a mouse model of chemotherapy-induced alopecia, this study found that inhibiting the protein S100A8 with paquinimod alleviated hair loss and reduced oxidative stress and ferroptosis, suggesting a potential therapeutic strategy for managing this side effect in chemotherapy patients. Our plain-language summary of this paper — not a Tressless recommendation.

This study investigates the role of S100A8 in chemotherapy-induced alopecia (CIA) through ferroptosis, a form of cell death, in a cyclophosphamide (CYP)-induced mouse model. Elevated levels of S100A8 were found to promote ferroptosis in outer root sheath keratinocytes (ORSKs) via the NCF2/NOX2 signaling pathway, contributing to hair follicle damage. The use of paquinimod (PAQ), an S100A8 inhibitor, reduced alopecia and markers of oxidative stress and ferroptosis. These findings suggest that targeting the S100A8–NCF2/NOX2 axis could be a promising therapeutic strategy for mitigating CIA, offering new insights into the molecular mechanisms of hair loss during chemotherapy.

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