Effect of 1.2-epoxy-3[3-3[3.4-dimetoxyiphenil]-4h-1-benzopiran-4-on] Propane (epi) on Sirtuin-1 and Nuclear Factor-kB Expression of DMBA induced Mammary Tumors in sprague dawley rats

Abstract: The main factors contribute in breast cancer development is the combination of exogenous and endogenous factors. Endogenous factors include both SIRT1 and NF-κB. Exogenous factor used in this research is DMBA. 1,2-epoxy-3[3-3[3,4-dimetoxy-phenil]-4h-1-benzophiran-4-on] propane (EPI) is a derivative of isoflavone generate from clove leaf oil.
Objectives: To examine the effect of EPI on SIRT1 and NF-κB expression in DMBA-induced Sprague Dawley rats, and to examine the correlation of SIRT1.
Methods: This experimental study with post-test only group design used 35 Sprague Dawley female rats with 2 weeks old. Those rats were divided into 7 groups (5 rats/group), namely normal control (1st group), corn oil group (2nd group), DMBA group (3rd group), EPI treated groups with 1 mg/kgBW, 2 mg/kgBW, and 4 mg/kgBW, respectively (4th, 5th, and 6th groups), and doxorubicin group (7th group). EPI and doxorubicin were given from 1st until 15th week, while DMBA were administered from 3rd until 9th week. At the end of week 15th, all rats were terminated and all of breast organs of each rats were taken to be prepared as paraffin block samples. Examination of SIRT1 and NF-κB expression was performed using light microscope at 400x magnification, after immunohistochemistry (IHC) staining. Expression of SIRT1 and NF-κB were analyzed using IHC-profiler plug-in in ImageJ software.
Results: Both SIRT1 and NF-κB expression in SD rat groups were given EPI has lower than DMBA group (p=0,000), and found there was no significant differences with Doxorubicin group. Furthermore, we found that there is a positive correlation between both SIRT1 and NF-κB expression (p=0,001; r=0,773) in EPI-treated SD that were induced by DMBA
Conclusions: EPI was able to prevent an increasing of SIRT1 and NF-κB expression in SD model breast cancer that induced with DMBA. There is a positive correlation between SIRT1 and NF-κB expression in EPI-treated SD rats that were induced by DMBA.
Keywords: Isoflavone, SIRT1 expression, NF-κB expression, breast cancer, EPI, DMBA, Sprague Dawley rats
Author: Ayyub Harly Nurung, Sri Herwiyanti, Dewi Kartikawati Paramita
Journal Code: jpkedokterangg160186