Uji Aktivitas Antikanker Payudara dan Kardioprotektif dari Ekstrak Etilasetat Daun Poguntano (Picria fel-terrae Lour.) dan Buah Andaliman (Zanthoxylum acanthopodium Dc.) yang Diinduksi Doksorubisin secara In-Vivo

Abstract

The use of doxorubicin (DOX) is effective as an antineoplastic in the treatment of breast cancer but it has side effects especially cardiotoxic irreversible. The cthyl acetate extract of leaves poguntano (EDP) and ethyl acetate extract of andaliman fruit (EEABA) have anti breast cancer activity through inhibition of cell cycle and apoptosis of the cells T47D and MCF-7 in vitro. The purposes of this studies were to determine the anti breast cancer and cardioprotective activities of EEADP and EEABA induced by doxorubicin in-vivo as well as antioxidant activity assay of EEADP and EEABA.

The extracts were made by maceration graded using solvents based on the level of polarity, starting from n-hexane and cthyl acetate and conducted the phytochemical screening and then characterization of crude simplex and extracts. The anticancer activity of EEADP and EEABA were tested to female mice. The doses given were 125 mg/kg bw and 250 mg/kg bw. Animals induced with BaP 2 times a weck for 4 weeks. Giving EEADP and EEABA were conducted from 1st week until the last observation (11 week). Then IHC examination of Ki-67 and caspase-3 and then scores of Ki-67 and caspase-3 expression were calculated. Cardioprotective activity were tested to female rats induced doxorubicin HCI dosing of 20 mg/kg on 8 and 9th days. EEABA and EEADP with dose of 300 mg/kg were given from 19 day until the 9th days. Measured levels of cTnT and CK-MB and cardiac histological examination. Antioxidant activity test of EEABA EEADP were done by using DPPH method. Concentration of each extract was 25 ppm, 50 ppm, 100 ppm, 200 ppm. Uptake of DPPH solution was measured using a visible spectrophotometer.

The results of Ki-67 score expression by EEADP and EEABA with dose of 125 mg/kg bw were 35.180 and 28.505; whereas caspase-3 score expression were 14.791 and 35.611. The Ki-67 score expression by EEADP and EEABA with dose of 250 mg/ kg bw were 30.349 and 17.428, where as caspase-3 score expression were 33,88 and 85,574. The higher dose of each extracts, the more inhibits Ki-67 expression and the higher increases caspase-3 expression. EEABA is more active as anticancer than EEADP. cTaT levels of EEADP + DOX and EEABA + DOX were 1.45 and 0.26 ; while CK-MB levels of EEADP + DOX and EEABA + DOX were 230 and 138. Histopathological analysis of rat's heart tissue of EEADP + DOX showed bleeding, fragmentation, and less of miositolisis; while EEABA + DOX group showed less of miositolisis and there were no some piknosis, bleeding, and fragmentations. The higher dose of cach extracts, the lower ¢TnT and CK-MB levels and the higher protective effect toward heart damage. EEABA is more active as cardioprotective than EEADP. In antioxidant activity, IC50 of EEADP were 115.038 ppm and IC5o of EEABA were 135.376 ppm.