Cell death induced by ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid in anaplastic thyroid carcinoma cells is via a mitochondrial-mediated pathway

Apoptosis. 2005 Dec;10(6):1345-56. doi: 10.1007/s10495-005-1730-5.

Abstract

The chemical compound ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), isolated from the Chinese herbal medicine plant Pteris semipinnata L, has been known to exert antitumor activity. However, the molecular mechanism of the action is not understood. In this study we demonstrated that apoptotic cell death induced by 5F in FRO cells was concentration- and time-dependent. The rapid increase in intracellular reactive oxygen species (ROS) levels was involved in the mechanism of cell death. c-Jun N-terminal kinase (JNK) activation and G2 block were related to cell death induced by 5F. Extracellular signal-related kinase (ERK) and p38 were also activated, but as survival signals in response to 5F treatment to counteract the induction of cell death. In the process of the induction of apoptotic cell death, Bax translocated into mitochondria, a reduction in Delta psi(m) was observed and a release of cytochrome c and apoptosis inducing factor (AIF) from mitochondria into the cytosol occurred, indicating that cell death induced by 5F was through a mitochondrial-mediated pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Inducing Factor / metabolism
  • Carcinoma / enzymology
  • Carcinoma / pathology*
  • Caspase 3 / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology*
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • G2 Phase / drug effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein Transport / drug effects
  • Reactive Oxygen Species / metabolism
  • Thyroid Neoplasms / enzymology
  • Thyroid Neoplasms / pathology*
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 11-hydroxy-15-oxokaur-16-en-19-olic acid
  • Apoptosis Inducing Factor
  • Diterpenes
  • Drugs, Chinese Herbal
  • Reactive Oxygen Species
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3