Oroxylin A inhibits UVB-induced non-melanoma skin cancer by regulating XPA degradation.
10.1016/S1875-5364(25)60893-4
- Author:
Renjie DOU
1
;
Jiarui SUN
2
,
3
;
Hang YANG
3
,
4
;
Yufen ZHENG
5
;
Kang YUAN
6
;
Lei QIANG
7
;
Run MA
8
;
Yunyao LIU
9
Author Information
1. State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: durester@outlook.com.
2. State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: sjiarui0401@
3. com.
4. The Third Department of Pharmacy, The First Affiliated Hospital of Henan Polytechnic University, Henan 454001, China. Electronic address: yanghanghpu@
5. Department of Basic Medicine and Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
6. School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
7. State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: lqiang@cpu.edu.cn.
8. Clinical Laboratory Department, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China. Electronic address: 467161115@qq.com.
9. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China. Electronic address: yunyaoliu@cpu.edu.cn.
- Publication Type:Journal Article
- Keywords:
GRP94;
MDM2;
Non-melanoma skin cancer;
Oroxylin A;
XPA
- MeSH:
Animals;
Ultraviolet Rays/adverse effects*;
Skin Neoplasms/prevention & control*;
Flavonoids/pharmacology*;
Mice;
Xeroderma Pigmentosum Group A Protein/genetics*;
Humans;
Proto-Oncogene Proteins c-mdm2/genetics*;
DNA Repair/drug effects*;
Scutellaria baicalensis/chemistry*;
Mice, Hairless;
Skin/radiation effects*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(6):742-753
- CountryChina
- Language:English
-
Abstract:
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.
