Vitamin D Protects Pancreatic Cancer (PC) Cells from Death and DNA Damage Induced by Oxidative Stress

In addition to its well-recognized roles in immunomodulation and calcium phosphate homeostasis, growing evidence shows that Vitamin D (Vit. D) presents a wide range of other properties, including antioxidant and anticancer effects. However, the action of Vit. D is not fully recognized in pancreatic cancer (PC) cells exposed to oxidative stress. Therefore, the aim of the present study was to investigate whether vitamin D₃ (Vit. D₃) protects PC cells from death induced by oxidative stress. PC cells are suggested to be resistant to oxidative stress since they demonstrate overexpression of superoxide dismutase (SOD) 1-3. The study measured PC cell viability, DNA damage level, the mRNA and protein expression of antioxidant enzymes, reactive oxygen species (ROS) level and activity of antioxidant enzymes after exposure to H₂O₂, Vit. D₃ and their combinations. N-Acetyl-L-Cysteine (NAC), a well-known direct ROS scavenger, was used as a positive control. Vit. D₃ exposure alone had no effect on PC cell viability, ROS level and DNA damage. Its impact on the mRNA and protein expression of antioxidant enzymes was also scarce. However, Vit. D₃ protected PC cells against H₂O₂-induced death, similarly to NAC. It also diminished the increase in ROS and DNA damage caused by H₂O₂. In addition, Vit. D₃ enhanced the mRNA expression of catalase (CAT), SOD 1-3 and glutathione peroxidase (Gpx)3, but did not affect their protein levels in PC cells exposed to oxidative stress. Interestingly, Vit. D₃ increased CAT activity after 24 h in 1.2B4 cells and elevated the activity of both CAT and Gpx after 2 h in PANC-1 cells, which could contribute to the observed reduction of H₂O₂-induced ROS level. To conclude, our findings show that antioxidant properties of Vit. D₃ may protect PC cells from oxidative stress-induced death. Therefore, further studies are needed to understand the action of Vit. D₃ in PC cells.