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Various concentrations of hesperetin induce different types of programmed cell death in human breast cancerous and normal cell lines in a ROS-dependent manner.

Abstract
The polyphenolic component of citrus fruits, hesperetin (Hst), is a metabolite of hesperidin. In this study, we examined the effect of varying doses and exposure times of hesperetin on MCF-7 and MDA-MB-231 cancer cells, as well as MCF-10A normal cells. By using MTT assay, real-time PCR, western blot, and flow cytometry, we determined the effects of Hst on cell viability, ROS levels, and markers of cell death. Furthermore, molecular docking was used to identify Hst targets that might be involved in ROS-dependent cell death. According to the results, different concentrations of Hst induced different modes of cell death at specific ROS levels. Paraptosis occurred in all cell lines at concentration ranges of IC35 to IC60, and apoptosis occurred at concentrations greater than IC65. In addition, MDA-MB-231 cells were subjected to senescence at sub-toxic doses when treated for a long period of time. When Hst levels were higher, N-acetylcysteine (NAC)'s effect on neutralizing ROS was more pronounced. According to the docking results, Hst may interact with several proteins involved in the regulation of ROS. As an example, the interaction of CCS (Copper chaperone for superoxide dismutase) with Hst might interfere with its chaperone function in folding SOD-1 (superoxide dismutase enzyme), contributing to an increase in cytoplasmic ROS levels. Finally, depending on the ROS level, Hst induces various modes of cell death.
AuthorsMohammad Rasoul Samandari-Bahraseman, Babak Khorsand, Sara Zareei, Massoud Amanlou, Hanieh Rostamabadi
JournalChemico-biological interactions (Chem Biol Interact) Vol. 382 Pg. 110642 (Sep 01 2023) ISSN: 1872-7786 [Electronic] Ireland
PMID37487865 (Publication Type: Journal Article)
CopyrightCopyright © 2023 Elsevier B.V. All rights reserved.
Chemical References
  • hesperetin
  • Hesperidin
  • Reactive Oxygen Species
  • Superoxide Dismutase
Topics
  • Humans
  • Female
  • Hesperidin (pharmacology)
  • Reactive Oxygen Species (metabolism)
  • Molecular Docking Simulation
  • Apoptosis
  • Cell Line, Tumor
  • Superoxide Dismutase (metabolism)
  • Breast Neoplasms

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