Homocysteine as an applied ER stress inducer in cancer: Dose-effects and side-effects analysis in HeLa cells

Endoplasmic reticulum (ER) stress induction is a promising approach in anti-cancer technologies, and homocysteine may serve as an effective agent. Its usage, however, may only be possible following thorough testing for signaling side-effects.In three independent experiments, HeLa cells were treated with two concentrations of homocysteine (1 mM and 3 mM) or vehicle for 24 h to assess the expression of XBP1 transcript variants and functioning of the NFE2L2/AP-1 and NFκB pathways.Homocysteine showed dose-dependent effectiveness in inducing ER stress and depleting total cellular thiols. The substance increased SESN2 expression when applied in the higher concentration. FTH1 expression differed between the two treatment groups. Surprisingly, no significant NFκB-associated effects were observed.Concluding on the results of the study, homocysteine can be used to effectively induce and manipulate ER stress and deplete cellular thiols. These effects are not necessarily accompanied by adverse effects in NFκB signaling.