Shikonin induces apoptosis in stomach carcinoma cells through regulation of P53 and NF-E2-related factor 2 (NRF2)

Shikonin, a naphthoquinone derivative found in the Lithospermum erythrorhizon, has known to inhibit various cancer cells proliferation. However its precise anti-cancer mechanisms of inducing cell death in stomach cancer. In this study, we investigated whether shikonin can induce to inhibit cell proliferation on human stomach carcinoma. Our results showed that shikonin was induced cell cycle arrest at the G2/M phase. Also, shikonin have induced activation of p53 which associated with oxidative stress. If the oxidative stress provokes DNA damage, cells respond to oxidative environment by activating the transcription of various antioxidant genes. NF-E2-related factor 2 (Nrf2) is doing pivotal role in against oxidative stress in cells. In case of this study, shikonin was increased activation of p53 but was decreased activation of Nrf2. Considering that p53 induced apoptosis requires an accumulation of reactive oxygen species, this negative control on the Nrf2 transactivation appears to be aimed to prevent the cytoprotection.