Epirubicin is widely used for the
therapy of various breast
cancers. However, it has serious adverse side effects, particularly
cardiotoxicity, which can cause irreversible damage in patients.
Paeonol, an active component from
Moutan Cortex, enhances antitumor activity of
antineoplastics and reduces toxicities induced by chemotherapeutics. In this study, we investigated the anticancer activity of
Paeonol in combination with
Epirubicin against
breast cancer and the alleviated effect of
Paeonol on
cardiotoxicity induced by
Epirubicin. The apoptosis results and the coefficient of drug interaction values suggested significantly synergistic in combination of
Paeonol and
Epirubicin to 4T1 and MCF-7 cells. We further examined antitumor activities of
Paeonol or/and
Epirubicin in vivo in BALB/c mice and found that co-treatment of
Paeonol and
Epirubicin had a synergistic inhibitory effect on
tumor growth and enhanced apoptosis in
tumors in vivo compared with
Epirubicin alone. Increased apoptosis was associated with the activation of apoptosis-related
proteins including PARP, Bax,
caspase 3, and inhibition of p38/JNK/ERK MAPKs. Moreover,
Paeonol exhibited a mitigative effect on
Epirubicin-induced
cardiotoxicity through suppressing
NF-kB pathway. In conclusion,
Paeonol (a) enhanced the antitumor activity of
Epirubicin in a synergistic manner against
breast cancer cells via inhibiting p38/JNK/ERK MAPKs and (b) alleviated
Epirubicin-induced
cardiotoxicity by suppressing
NF-kB pathway. These findings suggest that combination of
Paeonol and
Epirubicin is potentially applicable for
breast cancer treatment.