Allyl isothiocyanate confers resistance against low-pH stress conditions to RGM1 gastric normal epithelial cells

In this study, we attempted to elucidate the effects of ally isothiocyanates (AITC) on stress resistance. RGM1 cells, derived from the normal gastric mucosa of rats, were pretreated with AITC (0-30 μM) 24 hr or 48 hr prior to posttreatment with AITC (0 or 20 μM), or both. While approximately 90% of the vehicle-pretreated cells died by a posttreatment with AITC, pretreatments with AITC (10-30 μM), especially 24 hr prior and double pretreatments, exhibited striking cytoprotective effects. AITC, as a xenobiotic, increased the amounts of reactive oxygen species and insoluble proteins. On the other hand, double pretreatments with AITC markedly upregulated the mRNA expression levels of anti-oxidative, detoxification, and molecular chaperone genes for homeostasis. Interestingly, pretreatments with AITC (10 and 15 μM) significantly mitigated low-pH, but not high-pH, stress conditions, which may involve the activation of phosphoinositide 3-kinase and Na⁺/H⁺ exchanger. Taken together, we show here that multiple exposures to AITC can confer a stress resistance phenotype, including adaptation to acidic pH, by upregulating the expressions of self-defensive enzymes. Therefore, this study implies the importance of continuous ingestion of phytochemicals for efficiently increasing the stress resistance capacity against harmful chemicals.