Glutathione (gsh)

Piperlongumine (Selleck Chemicals, China) was dissolved in tween-80/water (10/90, v/v) at a final concentration of 0.5 mg/ml, and was administered to mice (5 mg/kg/d) daily via intraperitoneal injection according to corresponding therapeutic schedules. Glutathione (Selleck Chemicals, China) was dissolved in normal saline at a final concentration of 40 mg/ml, and was administered to mice (400 mg/kg/d) daily via intraperitoneal injection corresponding therapeutic schedules. Mannose (AbMole, China) was dissolved in 200 ml sterile water (20% (w/v)), which each mouse received a total amount of 40 g via normal drinking per week [13 (link)], supplemented with one dose of 40 mg by oral gavage three times per week. For αPD1 immunotherapy, αPD1 (clone RMP1-14, Bio X Cell) or its isotype control was administered to mice via intraperitoneal injection with a first dose of 400 µg/mouse and other doses of 200 µg/mouse every other day according to corresponding schedules (6 doses in total). Control animals received equivalent doses of isotype murine IgG according to the same dosing schedule.

Benzo[a]pyrene, benzo[k]fluoranthene, bosutinib, 1,2-dithiole-3-thione, flufenamic acid, MG132, PP2, Ro-31–8220 and hydrogen peroxide were purchased from Sigma-Aldrich (Taufkirchen, Germany), BPIQII, SR11302 and T-5224 from Cayman Chemicals (Ann Arbor, MI), and CH223191, cobimetinib and glutathione from Selleckchem (Houston, TX). Marimastat was purchased from Santa Cruz Biotechnology (Dallas, TX) and PD153035 from Absource Diagnostics (Munich, Germany). 3,3′,4,4′,5-Pentachlorobiphenyl (PCB126) and 2,3′,4,4′,5-pentachlorobiphenyl (PCB118) were bought from LGC Standards (Wesel, Germany) and 2,3,7,8-tetrachlorodibenzo-p-dioxin from Amchro (Hattersheim am Main, Germany). Prostaglandin D₂, AREG, TGFα and EGF were purchased from PeproTech (Rocky Hill, NY). hydrogen peroxide, glutathione and the three EGFR ligands were dissolved or diluted in water, the other compounds in DMSO. Treatment time and applied concentrations of the chemicals and human recombinant proteins is indicated in the figure legends.