Tumor Biology

, Volume 37, Issue 9, pp 12301–12313 | Cite as

Enhanced antitumor activity and attenuated cardiotoxicity of Epirubicin combined with Paeonol against breast cancer

Original Article
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Abstract

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.

Keywords

Epirubicin Breast cancer Paeonol Antitumor Cardiotoxicity 
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Notes

Acknowledgments

This work was supported by Shandong Provincial Natural Science Foundation (No. ZR2014HQ036).

Compliance with ethical standards

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Jing Wu
    • 1
    • 2
  • Xia Xue
    • 1
  • Bin Zhang
    • 1
  • Hongmei Cao
    • 3
  • Feng Kong
    • 4
  • Wen Jiang
    • 4
  • Juan Li
    • 1
  • Deqing Sun
    • 1
  • Ruichen Guo
    • 5
  1. 1.Department of PharmacyThe Second Hospital of Shandong UniversityJinanChina
  2. 2.Department of Pharmacology, School of MedicineShandong UniversityJinanChina
  3. 3.Department of PharmacyPeople’s Hospital of ZhangqiuJinanChina
  4. 4.Central LaboratoryThe Second Hospital of Shandong UniversityJinanChina
  5. 5.Institute of Clinical PharmacologyQi Lu Hospital of Shandong UniversityJinanChina

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