Co-treatment of Brazilein Enhances Cytotoxicity of Doxorubicin on WiDr Colorectal Cancer Cells Through Cell Cycle Arrest

BACKGROUND: The presence of adverse
side effects limits the use of doxorubicin
(Dox) despite its cost-effectiveness compared
to other chemotherapeutic agents. Brazilein (Be), the
major compound of Caesalpinia sappan, performs cochemotherapeutic
potency in several cancer cell lines. This
study evaluates the chemosensitizing effects of Be to Dox
on colon cancer cell line, WiDr.
METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyl-2H-tetrazolium bromide (MTT) assay was
conducted to evaluate the cytotoxic effect of Be and its
combination with Dox. The synergistic effect of Be and
Dox was examined by using the Combination index (CI)
parameter. Cell cycle and apoptosis profiles were done
using flow cytometry with propidium iodide (PI)/RNase
and Annexin V staining, respectively.
RESULTS: The combination of Dox and Be at half of
IC50 on WiDr cells showed a synergistic effect with a
combination index of 0.4. Analysis of the cell cycle revealed
that the combination caused cell cycle termination at the S
and G2/M phase. This finding corresponded with the data
that single treatment of Dox and Be induced cell cycle
arrest at the different phases, namely S and G2/M phase,
respectively. However, the combination treatment for 24
hours did not induce apoptosis. This combination should be
further clarified as there was a possibility that many cells
may underwent permanently arrest that halts to proceed
apoptosis.
CONCLUSION: Our findings suggested that Be synergizes
with Dox to suppress the growth of WiDr cells via cell
cycle arrest, hence, Be is potential to be developed as a cochemotherapeutic
agent. Our findings suggested that Be
synergizes with Dox to suppress the growth of WiDr cells
via cell cycle arrest, hence, Be is potential to be developed
as a co-chemotherapeutic agent.