Effects of interferon alpha 2b combined with vitamin K2 on liver carcinogenesis in mice

VERA, MC; LUCCI, A; LORENZETTI, MF; COMANZO, CG; HEIT-BARBINI, FJ; ALVAREZ, ML; QUIROGA, AD; CARRILLO, MC

Congreso; Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); 2021

Vitamin K2, which is present in dairy products, and it has been recommended as a micronutrient supplement in humans, holdsstrong anticancer properties. Interferon (IFN)-α-2b administered during development of hepatic preneoplasia decreased bothnumber and volume percentage of altered hepatic foci by increasing apoptosis within the foci. Objective: to evaluate whetherthe therapy of IFN-α-2b with vitamin K2 has a synergistic inhibitory action on DEN-induced hepatocarcinogenesis in mice.Methods and Results: 14-day-old mice were injected intraperitoneally (ip) with 25 mg/kg DEN (control group with tumor, CT).After 10 months mice were divided in groups: CT; IFN: CT mice treated with IFN-α-2b 6.5x105 U/kg ip 5 times/week/3 weeks; VK2:CT mice that received vitamin K2 5 mg/kg ip 5 times/week/3 weeks; and IFN+VK2: CT mice which received both drugs. Animalswere euthanized after treatments and livers were excised. We previously found that CT mice treated with IFN-α-2b had fewertumors/liver and a trend to be smaller in size (compared to CT livers). Also, immunoblotting analysis showed increaseproapoptotic Bax protein in IFN group respect to the CT group. In this study, cytochrome c levels (immunoblotting) increased inIFN group compared to CT animals (+125%*); the other groups did not show any differences respect to CT. The antiapoptoticprotein Bcl-2 showed an increase expression in VK2 and IFN+VK2 groups (+64%* and +75%*, respectively). Finally, we found thatlevels of antiapoptotic protein Bcl-XL were increased in IFN+VK2 group (+142%*) (*p<0.05 vs CT, n=5). Conclusion: Our findingsindicate that IFN-α-2b contributes to reducing liver tumor development in mice treated with DEN. Interestingly, vitamin K2 seemsto block the positive proapoptotic effect of IFN-α-2b. This is in agreement with our in vitro studies in SK-HEP-1 cells as well aswith our studies performed in in the early stages of liver cancer development in ra