Antitumor effects of two novel naturally occurring terpene quinones isolated from the Mediterranean ascidian Aplidium conicum

J Med Chem. 2005 May 5;48(9):3410-6. doi: 10.1021/jm0489915.

Abstract

The ascidian Aplidium conicum collected along Sardinia coasts (Italy) contained two novel prenylated benzoquinones, designated thiaplidiaquinone A (1) and thiaplidiaquinone B (2). These compounds showed an unprecedented tetracyclic structure. We have studied the pro-apototic mechanisms of both prenylated benzoquinones in the Jurkat cell line that is derived from a human T lymphoma, and we show that both compounds induce a strong production of intracellular reactive oxygen species (ROS) in this cell line. Moreover, kinetic experiments, comparing the timing of ROS induction with the collapse of the mitochondria potential (DeltaPsi(m)), clearly showed that ROS preceded the disruption of the mitochondrial potential, and the later one paralleled the appearance of apoptotic cells. Thus, thiaplidiaquinones A and B can enter into the cells and induce cell death by apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Benzoquinones / isolation & purification
  • Benzoquinones / pharmacology*
  • Humans
  • Jurkat Cells
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • Reactive Oxygen Species / metabolism
  • Terpenes / isolation & purification
  • Terpenes / pharmacology*
  • Thiazines / isolation & purification
  • Thiazines / pharmacology*
  • Urochordata / chemistry*

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • Reactive Oxygen Species
  • Terpenes
  • Thiazines
  • thiaplidiaquinone A
  • thiaplidiaquinone B