Neferine modulates IGF‐1R/Nrf2 signaling in doxorubicin treated H9c2 cardiomyoblasts. Issue 2 (5th October 2017)

• Record Type: Journal Article
• Authors: Bharathi Priya, Lohanathan; Baskaran, Rathinasamy; Huang, Chih‐Yang; Vijaya Padma, Viswanadha
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 2(2018)
• Page Start: 1441
• Page End: 1452
• Publication Date: 2017-10-05
• Subjects: doxorubicin -- IGF‐1R -- mitochondrial superoxide -- neferine -- Nrf2; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26305
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Doxorubicin (DOX) induced cardiotoxicity is a major problem during chemotherapy of cancers. DOX‐mediated suppression of type 1 IGF receptor (IGF‐1R) signaling leads to cardiac dysfunction. Neferine, a bisbezylisoquinoline alkaloid from the seed embryos of Nelumbo nucifera Gaertn possesses a distinct range of pharmacological properties. Herewith, the present study attempts to elucidate the protective role of neferine against DOX induced toxicity in H9c2 rat cardiomyoblast cell line model. DOX‐treated H9c2 cells significantly increased mitochondrial superoxide generation, depleted cellular antioxidant status, suppressed the activation of IGF‐1R signaling via PI3K/Akt/mTOR and induced autophagy by the activation of ULK1, Beclin1, Atg7, and LC3B. Neferine pre‐treatment activated IGF‐1R signaling, improved cellular antioxidant pool, increased the expression of down‐stream targets of IGF‐1R, such as PI3K/Akt/mTOR, inhibited mitochondrial superoxide generation and autophagy significantly with the induction of Nrf2 translocation and expressions of HO1 and SOD1. Our study suggests the use of neferine for amelioration of DOX‐mediated cardiotoxicity. Abstract : Doxorubicin induced cardiotoxicity is a major problem during chemotherapy of cancers. Neferine treatment activated IGF‐1R signaling, improved cellular antioxidant pool, increased the expression of down‐stream targets of IGF‐1R, PI3K/Akt/mTOR, inhibited mitochondrial superoxide generation and autophagy significantly with the induction of Nrf2 translocation and expressions of HO‐1 and SOD1.