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

Abstract

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.

• Authors: Jiguang Ma, Wanxing Duan, Suxia Han, Jianjun Lei, Qinhong Xu, Xin Chen, Zhengdong Jiang, Ligang Nan, Jiahui Li, Ke Chen, Liang Han, Zheng Wang, Xuqi Li, Erxi Wu, Xiongwei Huo
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 25 Pg. 20993-1003 (Aug 28 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25895130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Salicylates
• ginkgolic acid
• Fatty Acid Synthases
• AMP-Activated Protein Kinases
• Acetyl-CoA Carboxylase

Topics

• AMP-Activated Protein Kinases (metabolism)
• Acetyl-CoA Carboxylase (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, physiology)
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasm Invasiveness
• Neoplasms (pathology)
• Pancreatic Neoplasms (drug therapy, metabolism)
• RNA Interference
• Salicylates (chemistry)
• Signal Transduction