Targeting cell cycle by β-carboline alkaloids in vitro: Novel therapeutic prospects for the treatment of cancer

Chem Biol Interact. 2020 Oct 1:330:109229. doi: 10.1016/j.cbi.2020.109229. Epub 2020 Aug 21.

Abstract

Cell cycle dysregulation is the mainstay of aberrant cell proliferation, which leads to tumor progression. Mutations in tumor cells initiate various dysregulated pathways and spontaneous over-proliferation with genomic/chromosomal instability. Despite advances in cancer therapy, it has remained a medicinal challenge to treat. Besides, the complexity of pathophysiological pathways behind cancer raises the need for novel multi-target agents, possessing fewer side effects. Alkaloid-based therapies have been explored so far to target cell division in cancer, including vinca alkaloids. As a class of hopeful β-carboline derivatives, growing evidence has indicated their auspicious roles in combating cancer by inhibiting topoisomerase (TOPO), kinesin Eg5, telomerase, cyclin-dependent kinase (CDK), IκB kinase (IKK), and polo-like kinase-1 (PLK1) in the transition phases of cell cycle. In this review, in vitro potential of β-carboline has been revealed through targeting cell division cycle at different phases. In conclusion, β-carboline alkaloids could be introduced as novel candidates in cancer therapy.

Keywords: Alkaloids; Cancer treatment; Cell cycle; Therapeutic potential; β-carboline.

Publication types

  • Review

MeSH terms

  • Alkaloids / pharmacology
  • Alkaloids / therapeutic use
  • Carbolines / pharmacology*
  • Carbolines / therapeutic use
  • Cell Cycle / drug effects*
  • Cell Cycle Checkpoints / drug effects
  • Humans
  • Neoplasms / drug therapy*

Substances

  • Alkaloids
  • Carbolines