dc.description.abstract | Less optimized therapeutic effects constrain the use of doxorubicin as the main agent of chemotherapy for metastatic breast cancer, resistance
and side effects. Therefore we need a combination of more than one
chemopreventive agent which has different molecular targets to solve that
problem. The aims of this study is to prove the inhibitory effect of
ethanolic extract of rhizome of Curcuma xanthorrhiza (ECx), fruit of Brucea
javanica (EBj), leave of Ficus septica (EFs) and doxorubicin (Dox) alone and
its combination on migration and invasion of a highly metastatic 4T1
breast cancer cell line. Cytotoxic activity of single and combination
treatment was evaluated by MTT assay, followed by an experiment of
apoptosis induction by using flow cytometry. The inhibitory effect on
migration was observed by the scratch wound-healing assay. Furthermore,
the observation of the activity of matrix metalloproteinase-9 (MMP-9) was
analyzed by gelatin zymography. The results showed that ECx, EBj, EFs,
and Dox has cytotoxic activity on 4T1 cells with the value of IC50
respectively 49.7±1.53 g/mL, 59.9±1.79 g/mL, 15.2±2.12 g/mL and
1.2±0.23 M. Furthermore, the combination of ECx-EBj-Dox and ECx-EBjEFs
revealed a synergistic effect on 4T1 cells and decrease cell viability
through the induction of apoptosis and necrosis. Based on wound healing
assay, 24 hours incubation of this combination inhibited 4T1 cells
migration compared to single treatment. Gelatin zymography analysis
showed that this combination also inhibited the activity of MMP-9 greater
than a single use. Curcuma xanthorrhiza, Brucea javanica, and Ficus septica
may have potential to be developed as a combination with or without
doxorubicin for metastatic breast cancer treatment. | en_US |