| Summary: | Long term use of doxorubicin cause severe side effect such as toxic for
normal cells and cancer resistance. it is most desirable to have more effective new
drug by finding co-chemotherapy drugs. Co-chemotherapy is a cancer therapy
strategy, combine natural agent with chemotherapy drugs. This strategy can
reduce the side effect and toxicity of chemotherapy drugs. Brazilein, a compound
obtained in a large amount from the dried heartwood of secang (Caesalpinia
sappan L.), which has long been used in traditional medicine in Indonesia, has
some pharmacological activities especially in cancer. Study was designed to
isolate the brazilein compound from the dried heartwood of secang, determine the
cytotoxicity effect of brazilein and it`s combination with chemotherapy drug
(doxorubicin) using breast cancer (MCF-7 resistant) cell line as a model, and to
evaluate the molecular mechanism brazilein in Pgp, IKK and HER-2 by in silico
study using molecular docking
The methanolic extract of secang was purified by Liquid Liquid Extraction
(LLE) using hexane and ethylacetate. Brazilein was isolated from ethylacetat
fraction by a silica gel column,eluting with chloroform, ethylacetate and
methanol. Brazilein was characterized by IR, LC-MS (ESI), 1H, 13C NMR and
2D-NMR. In cytotoxic assay, resistant MCF-7 cells were cultured in the presence
of brazilein at various concentration for 24 h and the percentage of cell viability
was evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-di phenyl tetrazolium bromide) /
MTT assay. Interaction between the drug with the target proteins was performed
using molecular docking.
The infrared, mass spectra, 1H-NMR, 13-NMR and 2D-NMR signal
confirm that isolate is brazilein. The MTT assay result shows a dose-dependent
inhibition of cell proliferation with IC50 of 37 μM. Brazilein increases the
cytotoxic activity of doxorubicin in MCF-7 cells. This effect is confirmed by
docking in Pgp, IKK and HER-2, demonstrated interactions of compound to
protein with high affinity. It means that brazilein performed a potent cochemotherapy
agent. Futher study must be established to evaluate the molecular
mechanism of brazilein in vitro.
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