Background:
Cancer persists as one of the world’s most pressing maladies. Notable points about
chemotherapy are
drug side effects which are almost universally encountered. Emerging knowledge focusing on mechanisms of toxicity due to
chemotherapy has led to characterization of novel methods, including the exploitation of natural compounds, in combination
therapies.
Flavonoids are natural polyphenolic compounds that play protective roles against
tumor cell development. The focus of this study was apoptotic effects of two
flavonoids,
eupatorin and
salvigenin, in combination with
doxorubicin on a cellular model of
colon cancer. Method: Upon establishing a non-effective dose of
doxorubicin, and effective doses of
eupatorin (100μM) and
salvigenin (150μM) via MTT, morphological features of apoptosis were distinguished using
DAPI staining and cell cycle blockage in the sub-G1 phase. Apoptosis was determined by
annexin/ PI and western blotting. ROS levels and
MMP were measured to show any role of mitochondria in apoptosis. Results: Co-administration of
flavonoids with
doxorubicin induced apoptosis via the mitochondrial pathway as mitochondrial membrane potential and ROS production were changed.
Annexin/PI analysis demonstrated that apoptosis frequency was increased with the combination treatments in
colon cancer cells. Finally, the combination of these
flavonoids with
doxorubicin increased the Bax/Bcl-2 ratio,
caspase-3 expression and PARP cleavage. Conclusion: Combination of
flavonoids with
doxorubicin induces apoptosis and enhances effect on
cancer cells which might allow amelioration of side effects by dose lowering.