POTENTIAL OF COMPOUNDS 1,2-epoxy-3 [3- (3,4-dimetoksifenil) -4H-1-benzopyran-4on) propane AS ANTICANCER Studies in vitro Activity of Molecular Breast Cancer Cells T47D and MCF-7 as well as in vivo Molecular Activities animal Model induced-Dimetilbenz 7.12 (a) Anthracene

ABSTRACT: Cancer is one of the non-communicable diseases that became the main health problem in the world. The low success in cancer treatment is encourages researchers in the world competing for new anticancer through organic synthesize compounds as well as the explore active compounds from natural ingredients that have been empirically used by people to treat cancer. Synthetic isoflavone derivate compounds from feed stock of clove oil (eugenol) are widely available in Indonesia. Isoflavone derivate compounds with genistein and daidzein were successfully synthesized. The compounds is 1,2-Epoksi-3[3-3’4’-dimetoksifenil)-4H-1 benzopiran-4-on]propana. Although isoflavon derivate are successfully synthesized, but 1,2-Epoksi-3[3-3’4’-dimetoksifenil)-4H-1 benzopiran-4-on]propana compounds have not been studied about cytotoxic activity and molecular mechanism. Therefore the study of cytotoxic activity and molecular mechanism as anticancer activity for the compounds should be conducted. This compounds is active compound, which has the low IC50 than and is similar to doxorubicin and tamoxifen. Further, studies is to investigate the ability of the 1,2-Epoksi-3[3-3’4’-dimetoksifenil)-4H-1 benzopiran-4-on]propana compounds inhibit proliferation, stimulates the apoptotic of MCF-7 and T47D cell lines and inhibits the expression of COX-2 and VEGF in MCF-7 cell line and T47D cell line. In line with in vitro, the in vivo studies is to investigate the ability of the 1,2-Epoksi-3[3-3’4’-dimetoksifenil)-4H-1 benzopiran-4-on]propana compounds in inhibition the formation and growth of nodules on the breast of Spraque Dawley rat (SD) induced by DMBA and fixes the nodules histopathological overview formed on the breast of Spraque Dawley rat (SD) induced by DMBA. The barrier of the formation and growth of nodules and the normal histopathological overview of Spraque Dawley rat (SD) induced by DMBA and 1,2-Epoksi-3[3-3’4’-dimetoksifenil)-4H-1 benzopiran-4-on]propana compound is expected that it correlated with proliferation and angiogenesis occurence in the SD rat breast. So that this research also studies the ability of 1,2-Epoksi-3[3-3’4’-dimetoksifenil)-4H-1 benzopiran-4-on]propana compounds in inhibit the proliferation of cancer cells and angiogenesis on nodules formation on the breast of Spraque Dawley rats (SD) induced by DMBA. This experimental research with randomized post-test only control group design. In this study, 40 SD rats were divided into 8 groups. Group 1 is the control group, group 2 is the corn oil group, group 3 DMBA groups, groups 4, 5 and 6 are the treatment group of 1,2-Epoksi-3[3-3’4’-dimetoksifenil)-4H-1 benzopiran-4-on]propana compounds dosage of 1 mg / kg BW; 2 mg / kg and 4 mg / kg, respectively. While the group 7 and group 8 are doxorubicin and tamoxifen groups, respectively. The cell expressing Bcl-2, p53, COX-2, PCNA, VEGF protein and body weight of rats were analyzed using one way ANOVA. Observation the formation and growth of nodules and nodule duplicates were analyzed using survival /cox-regression.. Observations descriptive level of damage by hematoxylin eosin staining of breast tissue were analyzed using the Kruskal Wallis analysis. Rat breast cancer cells that express the PCNA and VEGF protein was analyzed using one way ANOVA. The research results showed the lower of PCNA, Bcl2, COX-2 and VEGF expression percentage and the higher p53 expression percentage in MCF-7 and T47D cell lines induces 1,2-Epoksi-3[3-3’4’-dimetoksifenil)-4H-1-benzopiran-4-on]propana compound In vivo study indicate that the giving of 1,2-Epoksi-3[3-3’4’-dimetoksifenil)-4H-1-benzopiran-4-on]propana compound is able to lower the percentage of breast nodule formation on DMBA induced rat. On rat groups getting with 1,2-Epoksi-3[3-3’4’-dimetoksifenil)-4H-1-benzopiran-4-on]propana compound exposure, the observed histological structure of breast rats was same with the normal group It was concluded. The potential synthetic isoflavone derivative compound is 1,2-Epoksi-3[3-(3,4-dimetoksifenil)-4H-1-benzopiran-4-on)propane compound which has in vitro moleculare anticancer mechanism on T47D and MCF-7 cell lines through inhibition of proliferation, induction of apoptosis, and the reduction of COX-2 and VEGF expression. The potential synthesis isoflavone derivative compound is 1,2-Epoksi-3[3-(3,4-dimetoksifenil)-4H1-benzopiran-4on]propana compound has in vivo anticancer activity through inhibition of nodul and enlargement of nodul as well as reparation of the histopathological breast of Spraque Dawley (SD) rats induced by DMBA. The 1,2-Epoksi-3[3-(3,4-dimetoksifenil)-4H-1-benzopiran-4-on)propana compound has in vivo moleculare anticancer mechanism through inhibition of cell proliferation and angiogenesis on the breast of Spraque Dawley rats (SD) induced by DMBA