Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis

Liu,Dawei; Zhao,Lei

doi:10.3892/etm.2022.11630

Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis

Authors:
- Dawei Liu
- Lei Zhao
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Affiliations: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shanxi 710032, P.R. China, Department of Nephropathy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shanxi 710032, P.R. China
Published online on: September 28, 2022 https://doi.org/10.3892/etm.2022.11630
Article Number: 694

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Abstract

Doxorubicin (Dox)‑induced myocardiopathy is a massive obstacle in administering chemotherapeutic drugs in cancer patients. In the present study, the effects of thymoquinone (TQ) on Dox‑induced cardiotoxicity were investigated in vitro. H9c2 cardiomyocytes were pre‑treated with TQ followed by Dox, and cell viability and cell death were subsequently measured. Flow cytometry was conducted to evaluate the apoptosis of H9c2 cells. Autophagy was assessed by immunofluorescence LC3 staining. Western blot analysis was performed to determine autophagy‑, apoptosis‑ and LKB1/AMPK‑related proteins. Dox‑induced H9c2 cell death and apoptosis were decreased after pretreatment with TQ in vitro. The number of autophagosomes and autophagic markers was further increased by TQ in the Dox‑treated H9c2 cells, which mediated LKB1/AMPK activation and the deactivation of mTOR. Suppression of autophagosomes abolished the TQ‑induced antiapoptotic effect. In conclusion, TQ reduces Dox‑induced apoptosis of cardiomyocytes by upregulating autophagy through activation of the LKB1/AMPK pathways. These novel results highlight the therapeutic potential of TQ to prevent Dox cardiotoxicity.

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