Bcl-2 modulation in p53 signaling pathway by flavonoids: A potential strategy towards the treatment of cancer

Noor Rahman, Haroon Khan, Asad Zia, Asifullah Khan, Sajad Fakhri, Michael Aschner, Karim Gul, Luciano Saso

Research output: Contribution to journalReview articlepeer-review

Abstract

Cancer is a major cause of death, affecting human life in both developed and developing countries. Numerous antitumor agents exist but their toxicity and low efficacy limits their utility. Furthermore, the complex pathophysiological mechanisms of cancer, serious side effects and poor prognosis restrict the administration of available cancer therapies. Thus, developing novel therapeutic agents are required towards a simultaneous targeting of major dysregulated signaling mediators in cancer etiology, while possessing lower side effects. In this line, the plant kingdom is introduced as a rich source of active phytochemicals. The secondary metabolites produced by plants could potentially regulate several dysregulated pathways in cancer. Among the secondary metabolites, flavonoids are hopeful phytochemicals with established biological activities and minimal side effects. Flavonoids inhibit B-cell lymphoma 2 (Bcl-2) via the p53 signaling pathway, which is a significant apoptotic target in many cancer types, hence suppressing a major dysregulated pathway in cancer. To date, there have been no studies reported which extensively highlight the role of flavonoids and especially the different classes of flavonoids in the modulation of Bcl-2 in the P53 signaling pathway. Herein, we discuss the modulation of Bcl-2 in the p53 signaling pathway by different classes of flavonoids and highlight different mechanisms through which this modulation can occur. This study will provide a rationale for the use of flavonoids against different cancers paving a new mechanistic-based approach to cancer therapy.

Original languageEnglish (US)
Article number11315
JournalInternational Journal of Molecular Sciences
Volume22
Issue number21
DOIs
StatePublished - Nov 1 2021

Keywords

  • Bcl-2
  • Cancer
  • Flavonoids
  • P53
  • Pharmacology
  • Signaling pathway
  • Therapeutic target

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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