BRAZILEIN INCREASES THE SENSITIVITY OF DOXORUBICIN ON MCF-7 RESISTANT DOXORUBICIN (MCF-7/DOX) CELLS THROUGH INHIBITION OF HER-2 ACTIVATION
Keywords:
Brazilein, Doxorubicin, Cytotoxic, HER-2 (3PP0), MCF-7DOX (Resistant MCF-7 Cells to Doxorubicin)Abstract
Objective: Brazilein is a compound obtained in a large amount from the dried heartwood of Secang (Caesalpinia sappan L.). Brazilein has strong cytotoxic effect in several cancer cell lines. This study was designed to evaluate the cytotoxic effect of combination brazilein with a chemotherapy agent, doxorubicin on MCF-7/DOX breast cancer cell lines and evaluate the molecular mechanism of brazilein by in silico using molecular docking to HER-2.
Methods: In the cytotoxicity assay, MCF-7/DOX cells were cultured in the presence of brazilein and doxorubicin for 24 hours and cell viability was evaluated by using MTT assay. Interactions between brazilein and the target protein, HER-2 (3PP0) was evaluated and calculated in silico by molecular docking using PLANTS.
Results: Brazilein increased doxorubicin's cytotoxic activity on MCF-7/DOX cells. Both of single treatment with different concentration brazilein 12.5 and 25 mM or doxorubicin 0.8 and 1 mM gave cell viability percentage above 80%, but combination of them led to decrease the cell viability percentage significantly. The score docking of brazilein was -77.73 kcal/mol and lapatinib value -71.34 kcal/mol.
Conclusion: Interaction between brazilein and HER-2 (3PP0) as protein target in breast cancer higher affinity than lapatinib as HER-2 drug. Brazilein performed as a potent co-chemotherapy agent for breast cancer treatment.
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References
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