Inhibition of Migration and Invasion of Hepatocarcinoma HepG2 Cells by Dietary Saponins via Targeting HIF-1α

Title:Inhibition of Migration and Invasion of Hepatocarcinoma HepG2 Cells by Dietary Saponins via Targeting HIF-1α

Volume: 18 Issue: 7

Author(s): Cheng Luo*, Di Wu, Meiling Chen, Wenhua Miao, Changfeng Xue, Yanhui Sun, Dequan Liu, Chong Xie, Yaqin Wang, Christopher Frenz and Shanggui Deng*

Affiliation:

• School of Food and Pharmacy, Zhejiang Ocean University, 1 Ocean University S. Rd., Lincheng New District, Zhoushan 316022, Zhejiang,China

• School of Food and Pharmacy, Zhejiang Ocean University, 1 Ocean University S. Rd., Lincheng New District, Zhoushan 316022, Zhejiang,China

Keywords: HepG2 cells, hypoxia, normaxia, RT-PCR, saponins, migration, invasion, HIF-1α.

Abstract: Abstract: Background: Different saponins from herbs have been used as tonic or functional foods, and for treatment of various diseases including cancers. Although clinical data has supported the function of these saponins, their underlying molecular mechanisms have not been well defined.

Methods: With the simulated hypoxia created by 8 hours of Cu++ exposure and following 24 hour incubation with different concentration of saponins in HepG2 cells for MTT assay, migration and invasion assays, and for RT-PCR, and with each group of cells for immunofluorescence observation by confocal microscopy.

Results：ZC-4 had the highest rate of inhibition of cell proliferation by MTT assay, and the highest inhibition of migration rate by in vitro scratch assay, while ZC-3 had the highest inhibition of invasion ratio by transwell assay. Under the same simulated hypoxia, the molecular mechanism of saponin function was conducted by measuring the gene expression of Hypoxia Inducible Factor (HIF)-1α through RT-PCR, in which ZC-3 showed a potent inhibition of gene HIF-1α. For the protein expression by immunofluorescence staining with confocal microscopy, HIF-1α was also inhibited by saponins, with the most potent one being ZC-4 after eight hours’ relatively hypoxia incubation.

Conclusion: Saponins ZC-4 and ZC-3 have the potential to reduce HepG2 cell proliferation, migration and invasion caused by hypoxia through effectively inhibiting the gene and protein expression of HIF-1α directly and as antioxidant indirectly

Cite this article as:

Luo Cheng *, Wu Di , Chen Meiling, Miao Wenhua, Xue Changfeng , Sun Yanhui, Liu Dequan, Xie Chong , Wang Yaqin , Frenz Christopher and Deng Shanggui *, Inhibition of Migration and Invasion of Hepatocarcinoma HepG2 Cells by Dietary Saponins via Targeting HIF-1α, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (7) . https://dx.doi.org/10.2174/1871520618666180110141827