Abstract
Ginkgo biloba L. has been used in traditional Chinese medicine (TCM) for thousands of years. However, the anti-cancer properties of ginkgolic acids (GAS) isolated from G. biloba 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 IC50 values ranging from 14.91 to 23.81 μg·mL−1. 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 G. biloba might represent promising Hsp90 inhibitors for the development of anti-nasopharyngeal carcinoma agents.
Highlights
In North Africa, Southeast Asia, and Southern China, nasopharyngeal carcinoma (NPC) has become the most frequent head and neck malignancy threatening human health [1,2]
We investigated whether their anti-cancer properties could be associated with the inhibition of cell proliferation, the suppression of migration and invasion, and the induction of apoptosis in CNE-2Z cells, as well as the inhibition of Heat shock protein 90 (Hsp90) chaperon function
hematoxylin and eosin (H&E) staining results showed that ginkgolic acids (GAS) did not damage organs such as the liver and kidney (Figure 2F). These results indicated that GAS might potentially be used as anti-tumor agents with low toxicity in vivo
Summary
In North Africa, Southeast Asia, and Southern China, nasopharyngeal carcinoma (NPC) has become the most frequent head and neck malignancy threatening human health [1,2]. Most patients with local NPC respond well to radiotherapy/ chemotherapy, with an improved 5 year survival rate (approximately 80%), distant metastasis and local recurrence are still primarily responsible for treatment failure and death associated with NPC [3,4]. For these reasons, novel therapeutic drugs and approaches with improved outcomes for advanced NPC are needed. Previous research has shown that Hsp inhibitors exhibit significant anti-tumor properties in NPC, such as the inhibition of cell growth, induction of apoptosis, and suppression of invasion and metastasis [6,13,14,15]. We launched a screening program for Hsp inhibitors from traditional Chinese medicine (TCM), and identified ginkgolic acids (GAS) from n-hexane extracts of the seed coat of Ginkgo biloba L
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