Ginkgolic acid suppresses the development of pancreatic cancer by inhibiting pathways driving lipogenesis

• Published in: Oncotarget Vol. 6; no. 25; pp. 20993 - 21003
• Main Authors: Ma, Jiguang, Duan, Wanxing, Han, Suxia, Lei, Jianjun, Xu, Qinhong, Chen, Xin, Jiang, Zhengdong, Nan, Ligang, Li, Jiahui, Chen, Ke, Han, Liang, Wang, Zheng, Li, Xuqi, Wu, Erxi, Huo, Xiongwei
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 28.08.2015
• Subjects: Acetyl-CoA Carboxylase - metabolism; AMP-Activated Protein Kinases - metabolism; Animals; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Fatty Acid Synthases - metabolism; Ginkgo biloba - chemistry; Hep G2 Cells; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Lipogenesis - drug effects; Lipogenesis - physiology; Male; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; Neoplasms - pathology; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Research Paper; RNA Interference; Salicylates - chemistry; Signal Transduction; cancer metabolism; ginkgolic acid (GA); pancreatic cancer; lipogenesis; AMP-activated protein kinase (AMPK)
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.3663

Ginkgolic acid (GA) is a botanical drug extracted from the seed coat of Ginkgo biloba L. with a wide range of bioactive properties, including anti-tumor effect. However, whether GA has antitumor effect on pancreatic cancer cells and the underlying mechanisms have yet to be investigated. In this study, we show that GA suppressed the viability of cancer cells but has little toxicity on normal cells, e.g, HUVEC cells. Furthermore, treatment of GA resulted in impaired colony formation, migration, and invasion ability and increased apoptosis of cancer cells. In addition, GA inhibited the de novo lipogenesis of cancer cells through inducing activation of AMP-activated protein kinase (AMPK) signaling and downregulated the expression of key enzymes (e.g. acetyl-CoA carboxylase [ACC], fatty acid synthase [FASN]) involved in lipogenesis. Moreover, the in vivo experiment showed that GA reduced the expression of the key enzymes involved in lipogenesis and restrained the tumor growth. Taken together, our results suggest that GA may serve as a new candidate against tumor growth of pancreatic cancer partially through targeting pathway driving lipogenesis.