Ginnalin A from Kujin tea (Acer tataricum subsp. ginnala) exhibits colorectal cancer chemoprevention effect via activation of Nrf2/HO-1 signaling pathway
Abstract
Ginnalin A (also known as acertannin), is one of the most important phenolic compounds of several beverage Acer plants. In this study, it is the first time to report that ginnalin A is an activator of the Nrf2 signaling pathway in human colon cancer cells. Ginnalin A, isolated from the leaves of Acer tataricum subsp. ginnala, exhibited promising preventive activity against colon cancer cells (HCT116, SW480 and SW620) with IC50 values of 24.8 μM, 22.0 μM, 39.7 μM, respectively. In addition, it significantly reduced the colony forming of these cells. Flow cytometry analysis indicated that ginnalin A suppressed cancer proliferation via induction of cell cycle arrest at the S-phase. Real time PCR analysis demonstrated that ginnalin A can upregulate the mRNA expression levels of Nrf2-related antioxidant genes Nrf2, HO-1 and NQO1. Western blotting analysis revealed that ginnalin A promoted the Nrf2 nuclear translocation and upregulated the protein Nrf2, HO-1 and NQO1. Moreover, upregulation of p62 and inhibition of Keap1 were also found by Western blotting analysis. Therefore, the activation of Nrf2 signaling pathway was probably induced through upregulation of p62 and inhibition of Keap1.