Gingerenone A Induces Antiproliferation and Senescence of Breast Cancer Cells

Ginger is a popular spice and consists of several bioactive antioxidant compounds. Gingerenone A (Gin A), a novel compound isolated from Zingiber officinale, is rarely investigated for its anti-breast-cancer properties. Some ginger extracts have been reported to initiate senescence, an Anticancer strategy. However, the Anticancer effects of Gin A on breast Cancer cells remain unclear. The present study aims to assess the modulating impact of Gin A acting on proliferation and senescence to breast Cancer cells. Gin A diminished the cellular ATP content and decreased the cell viability of the MTS assay in several breast Cancer cell lines. It also showed a delayed G2/M response to breast Cancer cells (MCF7 and MDA-MB-231). N-acetylcysteine (NAC), an oxidative stress inhibitor, can revert these responses of antiproliferation and G2/M delay. The oxidative stress and senescence responses of Gin A were further validated by increasing Reactive Oxygen Species, mitochondrial superoxide, and β-galactosidase activity, which were reverted by NAC. Gin A also upregulated senescence-associated gene expressions. In addition to oxidative stress, Gin A also induced DNA damage responses by increasing γH2AX level and foci and generating 8-hydroxyl-2'-deoxyguanosine in breast Cancer cells, which were reverted by NAC. Therefore, Gin A promotes antiproliferation and senescence of breast Cancer cells induced by oxidative stress.