Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice

Vinodkumar B. Pillai, Abhinav Kanwal, Yong Hu Fang, Willard W. Sharp, Sadhana Samant, Jack Arbiser, Mahesh P. Gupta

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Doxorubicin is the chemotherapeutic drug of choice for a wide variety of cancers, and cardiotoxicity is one of the major side effects of doxorubicin treatment. One of the main cellular targets of doxorubicin in the heart is mitochondria. Mitochondrial sirtuin, SIRT3 has been shown to protect against doxorubicin-induced cardiotoxicity. We have recently identified honokiol (HKL) as an activator of SIRT3, which protects the heart from developing pressure overload hypertrophy. Here, we show that HKLmediated activation of SIRT3 also protects the heart from doxorubicin-induced cardiac damage without compromising the tumor killing potential of doxorubicin. Doxorubicin-induced cardiotoxicity is associated with increased ROS production and consequent fragmentation of mitochondria and cell death. HKL-mediated activation of SIRT3 prevented Doxorubicin induced ROS production, mitochondrial damage and cell death in rat neonatal cardiomyocytes. HKL also promoted mitochondrial fusion. We also show that treatment with HKL blocked doxorubicin-induced cardiac toxicity in mice. This was associated with reduced mitochondrial DNA damage and improved mitochondrial function. Furthermore, treatments of mice, bearing prostrate tumor-xenografts, with HKL and doxorubicin showed inhibition of tumor growth with significantly reduced cardiac toxicity. Our results suggest that HKL-mediated activation of SIRT3 protects the heart from doxorubicin-induced cardiotoxicity and represents a potentially novel adjunct for chemotherapy treatments.

Original languageEnglish
Pages (from-to)34082-34098
Number of pages17
JournalOncotarget
Volume8
Issue number21
DOIs
Publication statusPublished - 01-01-2017

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Sirtuin 3
Heart Mitochondria
Cardiomyopathies
Doxorubicin
Neoplasms
honokiol
Cell Death
Mitochondrial Dynamics
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Pillai, Vinodkumar B. ; Kanwal, Abhinav ; Fang, Yong Hu ; Sharp, Willard W. ; Samant, Sadhana ; Arbiser, Jack ; Gupta, Mahesh P. / Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice. In: Oncotarget. 2017 ; Vol. 8, No. 21. pp. 34082-34098.
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Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice. / Pillai, Vinodkumar B.; Kanwal, Abhinav; Fang, Yong Hu; Sharp, Willard W.; Samant, Sadhana; Arbiser, Jack; Gupta, Mahesh P.

In: Oncotarget, Vol. 8, No. 21, 01.01.2017, p. 34082-34098.

Research output: Contribution to journalArticle

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