인간 폐암세포 A549에서 Nrf2 및 Nrf2에 의해 조절되는 단백질에 대한 Ginsenoside Rg3의 효과

Abstract

The Nrf2 signaling plays an important role in regulating cellular defense system. Under normal cellular conditions, Nrf2 can be described as an anti-tumor molecule inducing antioxidative and cytoprotective genes which protect cells from electrophile and oxidative damage. However, in cancerous cells, Nrf2 takes on a pro-tumoral identity as the same cytoprotective genes can enhance resistance of cancer cells to chemotherapeutic drugs. We investigated whether Rg3 could inhibit Nrf2-mediated defense systems in A549 human lung cancer cells with constitutively overexpressed Nrf2. Rg3 decreased cell viability in a dose-dependent manner. Rg3 inhibited the expression of Nrf2 and its downstream proteins, HO-1, NQO-1, Ճ-GCS and MRP-1 in a time- and dose-dependent manner in A549 cells. In both cytoplasmic and nuclear fractions, Rg3 decreased Nrf2 and pNrf2 levels. In immunocytochemical analysis, Nrf2 showed a significantly decreased level in nucleus of A549 cells treated with Rg3 for 4 h. Furthermore, the combined treatment with Rg3 and cisplatin enhanced cytotoxicity in A549 cells compared with cisplatin or Rg3-treated cells. Taken together, Rg3 reduces Nrf2 nuclear level by inhibiting its expression and translocation into nucleus. This effect may be closely associated with the cytotoxicity of Rg3 and the increased cytotoxicity of cisplatin in Rg3-treated A549 cells.