Dou Renjie, Sun Jiarui, Yang Hang, Zheng Yufen, Yuan Kang, Qiang Lei, Ma Run, Liu Yunyao. Oroxylin A inhibits UVB-induced non-melanoma skin cancer by regulating XPA degradation[J]. Chinese Journal of Natural Medicines. DOI: 10.1016/S1875-5364(24)60660-6
Citation: Dou Renjie, Sun Jiarui, Yang Hang, Zheng Yufen, Yuan Kang, Qiang Lei, Ma Run, Liu Yunyao. Oroxylin A inhibits UVB-induced non-melanoma skin cancer by regulating XPA degradation[J]. Chinese Journal of Natural Medicines. DOI: 10.1016/S1875-5364(24)60660-6

Oroxylin A inhibits UVB-induced non-melanoma skin cancer by regulating XPA degradation

  • Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA’s interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
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