Cell cycle modulatory effects of Amaryllidaceae alkaloids

Life Sci. 2018 Nov 15:213:94-101. doi: 10.1016/j.lfs.2018.08.073. Epub 2018 Sep 1.

Abstract

The birth, growth, proliferation and death of cells involve a rigorous and continuous process in place to ensure the survival of living organisms. The cell cycle prevails at the core of this process to facilitate the division of a parent cell as well as the duplication of its genetic matter. Although checkpoints exist to steer the course of a cell from one phase to the other, malfunctions at any point of the four active phases of the cell cycle can have detrimental effects. Cancer is thought to be a consequence of such a malfunction in the cell cycle which endows a cell with enhanced replicative potential, immunity to anti-growth signals and the ability to evade apoptosis. This characteristic has been exploited in cancer chemotherapy since a significant number of anticancer drugs manifest their action via cell cycle modulatory effects. The plant family Amaryllidaceae is distinguished for its alkaloid principles which exhibit potent (at the sub-nanomolar level in some cases) and cell line specific antiproliferative activities, with apoptosis induction a key feature of these properties. As a consequence there has been sustained interest in these chemical entities as a source of new anticancer drugs. This has been matched by the large body of work that has emerged over the past two decades addressing their cytotoxic potential, establishing a structure-activity relationship basis as well as probing their mode of action. This review focuses on studies which highlight how Amaryllidaceae alkaloids modulate the cell cycle of cancer cells.

Keywords: Alkaloid; Amaryllidaceae; Cancer; Cell cycle; Modulation.

Publication types

  • Review

MeSH terms

  • Alkaloids / pharmacology
  • Amaryllidaceae Alkaloids / metabolism*
  • Amaryllidaceae Alkaloids / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle / drug effects*
  • Cell Cycle Checkpoints / drug effects
  • Humans
  • Neoplasms / drug therapy
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Amaryllidaceae Alkaloids
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic