1,2,4-Trihydroxybenzene

1,2,4-Trihydroxybenzene (Hydroxyhydroquinone) is an ER stress inducer that targets proteins such as PKR-like ER kinase PERK to induce cytotoxicity. 1,2,4-Trihydroxybenzene selectively activates eIF2α phosphorylation, activates the PERK-eIF2α signaling pathway and induces stress granule formation. 1,2,4-Trihydroxybenzene subsequently exacerbates oxidative stress and causes DNA double-strand breaks, destroying organelles such as mitochondria and ER, and inducing cell death. 1,2,4-Trihydroxybenzene also has the potential to exhibit anti-tumor effect, increase blood pressure, and relieve spasm^[1][2][3][4]. In Vitro:1,2,4-Trihydroxybenzene (HHQ) (10-100 μM; 2-4 h) increases intracellular Ca²⁺ concentration, induces membrane potential hyperpolarization and activates Ca²⁺-dependent K⁺ channels in rat thymic lymphocyte experiments^[1].
1,2,4-Trihydroxybenzene (THB) (50-800 μM; 24 h) dose-dependently reduces the cell viability of human keratinocytes (HaCaT) and induces stress granule formation and eIF2α/PERK phosphorylation. Continued treatment with 1,2,4-Trihydroxybenzene (THB) (50-800 μM; 1 h, followed by 24 h recovery) leads to DNA damage and apoptosis^[2].
1,2,4-Trihydroxybenzene (20-40 μg/mL; 6-24 h) significantly inhibits the cell viability of HeLa [Chang liver] (human Chang liver cells), induces G2/M phase arrest, and non-apoptotic cell death, accompanied by mitochondrial structural destruction and increasing ROS levels^[3]. In Vivo:1,2,4-Trihydroxybenzene (1-10 mg/kg; intravenous injection; single dose) increases blood pressure and enhances catecholamine production in anesthetized dogs^[4].