biostudies-literaturePan XKey Technology Research and Development Program of ShandongNatural Science Foundation of Shandong ProvinceNational Natural Science Foundation of China8179-8186https://www.ebi.ac.uk/biostudies/studies/S-EPMC6836941biostudies-literatureUnknown10(35)Reductive stress, the opposite of oxidative stress, represents a disorder in the redox balance state which is harmful to biological systems. For decades, the role of oxidative stress in tumor therapy has been the focus of attention, while the effects of reductive stress have been rarely studied. Here, we report the anti-cancer effects of reductive stress induced by three natural antioxidants (resveratrol, curcumin and celastrol). Considering the fact that the solid tumor microenvironment suffers from hypoxia, we performed cell experiments under hypoxic conditions. In order to observe the reductive stress, we first developed an ultrasensitive fluorescent probe (TCF-MQ) for specifically imaging NAD(P)H which is a marker of reductive stress. TCF-MQ responded to NAD(P)H rapidly and exhibited hChemical scienceMonitoring NAD(P)H by an ultrasensitive fluorescent probe to reveal reductive stress induced by natural antioxidants in HepG2 cells under hypoxia.PMC6836941ZR2014JL055217750919175311121535004215750812018YFJH0502Pan XCheng TXu KZang LTang BZheng AZhao YGe AfalseMonitoring NAD(P)H by an ultrasensitive fluorescent probe to reveal reductive stress induced by natural antioxidants in HepG2 cells under hypoxia.Reductive stress, the opposite of oxidative stress, represents a disorder in the redox balance state which is harmful to biological systems. For decades, the role of oxidative stress in tumor therapy has been the focus of attention, while the effects of reductive stress have been rarely studied. Here, we report the anti-cancer effects of reductive stress induced by three natural antioxidants (resveratrol, curcumin and celastrol). Considering the fact that the solid tumor microenvironment suffers from hypoxia, we performed cell experiments under hypoxic conditions. In order to observe the reductive stress, we first developed an ultrasensitive fluorescent probe (TCF-MQ) for specifically imaging NAD(P)H which is a marker of reductive stress. TCF-MQ responded to NAD(P)H rapidly and exhibited h2019-01-01T00:00:00Z2019 Sep2025-05-29T21:29:02.592Z2025-05-29T21:29:02.592ZS-EPMC68369413185788410.1039/c9sc02020a