ROS-mediated activation of AMPK plays a critical role in sulforaphane-induced apoptosis and mitotic arrest in AGS human gastric cancer cells

Rok, strany: 2018, 129 - 140

In this study, we investigated the role of AMP-activated protein kinase (AMPK) and the importance of reactive oxygen species (ROS) in apoptosis induction associated with cell cycle arrest induced by sulforaphane in AGS human gastric cancer cells. Our results demonstrated that sulforaphane inhibited proliferation of AGS cells by promoting apoptosis and accumulating the cellular portion of the G2/M phase via the buildup of cyclin B1 and cyclin-dependent kinase p21 (WAF1/CIP1). Moreover, the phosphorylation of histone H3 was markedly increased following treatment with sulforaphane, indicating that sulforaphane stimulated mitotic arrest. Sulforaphane concurrently induced phosphorylation of AMPK; however, compound C, an AMPK inhibitor, significantly blocked sulforaphane-induced apoptosis, suggesting that sulforaphane induces apoptosis of AGS cells through the AMPK-dependent pathway. Sulforaphane also activated the mitochondrial apoptotic signaling pathway with a decrease in mitochondrial membrane potential and the nuclear translocation of cytochrome c. Furthermore, sulforaphane provoked the generation of intracellular ROS; especially when ROS production was blocked by antioxidant N-acetylcysteine, both AMPK activation and growth inhibition by sulforaphane were completely abolished. Collectively, these findings suggest that sulforaphane inhibited growth of AGS cells, which was mediated by a complex interplay between cellular mechanisms governing redox homeostasis, apoptosis, and cell cycle arrest through an ROS/AMPK-dependent pathway.

ISO 690:

Choi, Y. 2018. ROS-mediated activation of AMPK plays a critical role in sulforaphane-induced apoptosis and mitotic arrest in AGS human gastric cancer cells. In General Physiology and Biophysics, vol. 37, no.2, pp. 129-140. 0231-5882.

APA:

Choi, Y. (2018). ROS-mediated activation of AMPK plays a critical role in sulforaphane-induced apoptosis and mitotic arrest in AGS human gastric cancer cells. General Physiology and Biophysics, 37(2), 129-140. 0231-5882.