EFFECT OF ISOFLAVONE DERIVATE 1,2-EPOKSI-3- [3-(3.4-DIMETOKSIFENIL)-4H-1-BENZOPIRAN-4-ON] PROPANE ON P53 EXPRESSION FROM BREAST CANCER MODEL OF SPRAQUE DAWLEY RAT INDUCED BY DMBA 

ABSTRACT: Background : Cancer is the main cause of worldwide death on the last 5 years. In Indonesia, breast cancer has the highest mortality rate among other cancer types. Mutation on p53 gene being one of cancer development's key factor. Among anticancer substances that to be developed from natural compound, Isoflavone being the most potential candidate. 1,2-Epoksi-3[3-(3'4'-dimetoksifenil)-4H-1-Benzopiran-4-on]propane (EPI), one of Isoflavon derivate substance, is assumed to have an anticancer effect. Objectives : To understand the effect of EPI substance on mutant p53 expression from breast cancer model in the aspect of Sprague Dawley rat induced by DMBA. Methods : Subjects used in this research are 35 female Sprague Dawley rat aged Ã��Ã�±3 months with weight of Ã��Ã�±40 gram and randomly distributed into 7 different groups. Control group was the group that fed only. Oil group was given with corn oil as DMBA solver. DMBA group that was given 2x20 mg/kgBW of DMBA for 5 weeks, was a cancer positive group. EPI 1 mg group was cancer model rat that given isoflavone 1 mg/kgBW for 15 weeks. EPI 2 mg group was a group of cancer model given 2 mg/kgBW of isoflavone for 15 weeks. EPI 4 mg group was a group of cancer model given 4 mg/kgBW of Isoflavone substance for 15 weeks. Doxorubicin group was a group of cancer model given with 0,6 mg/kgBW of Doxorubicin as conventional anticancer drug for 15 weeks. At the end of the 16th week, rats were decapitated and its nodule were removed then were prepared to be histological sample stained by mutant p53 IHC. Results : DMBA caused the increase of p53 expression compared to control group(p<0,05). Doxorubicin as anticancer drug decreased the mutant p53 expression (p<0,05). The isoflavone substances at all doses caused depletion of mutant p53 expression if compared to DMBA group's (p<0,05). The isoflavone substance administration at 3 different doses was not significaly different to decrease the mutant p53 expression compared to doxorubicin group(p>0,05). Conclusion : Administration of Isoflavone substance at 1 mg/kgBW, 2 mg/kgBW, and 4 mg/kgBW dose decreased the p53 expression and shown a non significance different anticancer activities with doxorubicin that known as conventional anticancer drug.