Melatonin Antagonizes Nickel-Induced Aerobic Glycolysis by Blocking ROS-Mediated HIF-1αmiR210ISCU Axis Activation

Abstract EN

Nickel and its compounds, which are well-documented carcinogens, induce the Warburg effect in normal cells by stabilizing hypoxia-inducible factor 1α (HIF-1α).

Melatonin has shown diverse anticancer properties for its reactive oxygen species- (ROS-) scavenging ability.

Our aim was to explore how melatonin antagonized a nickel-induced increment in aerobic glycolysis.

In the current work, a normal human bronchial epithelium cell line (BEAS-2B) was exposed to a series of nonlethal doses of NiCl2, with or without 1 mM melatonin.

Melatonin attenuated nickel-enhanced aerobic glycolysis.

The inhibition effects on aerobic glycolysis were attributed to the capability of melatonin to suppress the regulatory axis comprising HIF-1α, microRNA210 (miR210), and iron-sulfur cluster assembly scaffold protein (ISCU1/2).

N-Acetylcysteine (NAC) manifested similar effects as melatonin in scavenging ROS, maintaining prolyl-hydroxylase activity, and mitigating HIF-1α transcriptional activity in nickel-exposed cells.

Our results indicated that ROS generation contributed to nickel-caused HIF-1α stabilization and downstream signal activation.

Melatonin could antagonize HIF-1α-controlled aerobic glycolysis through ROS scavenging.