Anti-Cancer Properties of Ginkgolic Acids in Human Nasopharyngeal Carcinoma CNE-2Z Cells via Inhibition of Heat Shock Protein 90

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 21; p. 6575
• Main Authors: Li, Hong-Mei, Ma, Hui, Sun, Xiaolong, Li, Bohan, Cao, Chengjiang, Dai, Yiqun, Zhu, Meilin, Wu, Cheng-Zhu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.10.2021; MDPI
• Subjects: Adenosine triphosphatase; AKT protein; Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Bcl-2 protein; Cancer therapies; Cell growth; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Chinese medicine; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; ErbB-2 protein; Female; Gelatinase A; Gelatinase B; Ginkgo biloba - chemistry; ginkgolic acids; Heat shock proteins; Hepatotoxicity; Herbal medicine; Hsp90; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Humans; Hydrogen bonds; Hydrophobicity; Inhibitors; invasion; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; migration; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - drug therapy; Nasopharyngeal Carcinoma - metabolism; Nasopharyngeal Carcinoma - pathology; Nasopharyngeal Neoplasms - drug therapy; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Raf protein; Salicylates - chemistry; Salicylates - isolation & purification; Salicylates - pharmacology; Throat cancer; Tumor cell lines; Tumor Cells, Cultured; Tumors; Xenografts; China; Hsp90; migration; apoptosis; ginkgolic acids; nasopharyngeal carcinoma; invasion
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26216575

L. has been used in traditional Chinese medicine (TCM) for thousands of years. However, the anti-cancer properties of ginkgolic acids (GAS) isolated from have not been investigated in human nasopharyngeal carcinoma cells. In this study, GAS exhibited an inhibitory effect on the ATPase activity of heat shock protein 90 (Hsp90) and anti-proliferative activities against four human cancer cell lines, with IC values ranging from 14.91 to 23.81 μg·mL . In vivo experiments confirmed that GAS inhibited tumor growth in CNE-2Z cell-xenografted nude mice with low hepatotoxicity. We further demonstrated that GAS suppressed migration and invasion and induced the apoptosis of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (MMP-2, MMP-9, Her-2, c-Raf, Akt, and Bcl-2). Together, GAS are new Hsp90 inhibitors by binding to Hsp90 (hydrogen bond and hydrophobic interaction). Thus, GAS from might represent promising Hsp90 inhibitors for the development of anti-nasopharyngeal carcinoma agents.