Deguelin targets multiple oncogenic signaling pathways to combat human malignancies

Pharmacol Res. 2021 Apr:166:105487. doi: 10.1016/j.phrs.2021.105487. Epub 2021 Feb 11.

Abstract

Cancer is an anomalous growth and differentiation of cells known to be governed by oncogenic factors. Plant-based natural metabolites have been well recognized to possess chemopreventive properties. Deguelin, a natural rotenoid, is among the class of bioactive phytoconstituents from a diverse range of plants with potential antineoplastic effects in different cancer subtypes. However, the precise mechanisms of how deguelin inhibits tumor progression remains elusive. Deguelin has shown promising results in targeting the hallmarks of tumor progression via inducing tumor apoptosis, cell cycle arrest, and inhibition of angiogenesis and metastasis. Based on initial scientific excerpts, deguelin has been reported to inhibit tumor growth via different signaling pathways, including mitogen-activated protein kinase, phosphoinositide 3-kinase, serine/threonine protein kinase B (also known as Akt), mammalian target of rapamycin, nuclear factor-κB, matrix metalloproteinase (MMP)-2, MMP-9 and caspase-3, caspase-8, and caspase-9. This review summarizes the mechanistic insights of antineoplastic action of deguelin to gain a clear understanding of its therapeutic effects in cancer. The anticancer potential of deguelin with respect to its efficacy in targeting tumorigenesis via nanotechnological approaches is also investigated. The initial scientific findings have presented deguelin as a promising antitumorigenic agent which can be used for monotherapy as well as synergistically to augment efficacy of chemotherapeutic treatment regimes.

Keywords: Angiogenesis inhibition; Anti-inflammation; Antiproliferation; Apoptotic; Deguelin; Metastasis inhibition.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects
  • Carcinogenesis / drug effects*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Proliferation / drug effects
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Rotenone / analogs & derivatives*
  • Rotenone / pharmacology
  • Rotenone / therapeutic use
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents, Phytogenic
  • Rotenone
  • deguelin