The Role of mTOR in Doxorubicin-Altered Cardiac Metabolism: A Promising Therapeutic Target of Natural Compounds

Cardiovasc Toxicol. 2024 Feb;24(2):146-157. doi: 10.1007/s12012-023-09820-7. Epub 2023 Dec 18.

Abstract

Doxorubicin (DOX) is commonly used for the treatment of various types of cancer, however can cause serious side effects, including cardiotoxicity. The mechanisms involved in DOX-induced cardiac damage are complex and not yet fully understood. One mechanism is the disruption of cardiac metabolism, which can impair cardiac function. The mammalian target of rapamycin (mTOR) is a key regulator of cardiac energy metabolism, and dysregulation of mTOR signaling has been implicated in DOX-induced cardiac dysfunction. Natural compounds (NCs) have been shown to improve cardiac function in vivo and in vitro models of DOX-induced cardiotoxicity. This review article explores the protective effects of NCs against DOX-induced cardiac injury, with a focus on their regulation of mTOR signaling pathways. Generally, the modulation of mTOR signaling by NCs represents a promising strategy for decreasing the cardiotoxic effects of DOX.

Keywords: Autophagy; Cardiotoxicity; Doxorubicin; mTORC1; mTORC2.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Autophagy
  • Cardiotoxicity* / metabolism
  • Doxorubicin / toxicity
  • Humans
  • Myocytes, Cardiac
  • Oxidative Stress
  • Sirolimus*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Sirolimus
  • Doxorubicin
  • TOR Serine-Threonine Kinases