Abstract

Zerumbone, a sesquiterpene compound occurring in tropical ginger Zingiber zerumbet Smith, was shown to attenuate the ⁶⁰Co γ-rays irradiation-induced cell damage and cell apoptosis in HEK 293 cells. The γ-H2AX focus formation and the protein expression levels, which were important markers of ionizing radiation-induced DNA double-strand breaks, were significantly inhibited too. To elucidate the mechanism via which Zerumbone exerts its cell protective activity, the effects of this compound on Keap1/Nrf2/ARE pathway, which are cellular sensors of chemical- and radiation-induced oxidative and electrophilic stress, were next assayed. The results showed that 5 to 20 μM of Zerumbone could increase Nrf2 protein levels, bring about a dose-dependent induction in ARE-dependent transcriptional activity and subsequently up-regulate the expression of phase II detoxifying enzymes of NQO1 and HO-1. When 1 μM of ATRA, an ARE response inhibitor, was co-administrated, the Zerumbone inductions in ARE-dependent transcriptional activity and HO-1 up-regulation were almost abolished. As a result, the protective effects of Zerumbone on irradiation-induced cell apoptosis and DNA damage were significantly attenuated. These results, taken together, suggested that Zerumbone could protect HEK 293 cells from irradiation-induced cell apoptosis and DNA damage via, at least partly, activating the Keap1/Nrf2/ARE pathway.

Key words: Zerumbone, DNA double-strand break, γ-H2AX, HEK 293 cell, HO-1, NQO1, antioxidant response element.