Delta9-tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism

FEBS Lett. 1999 Sep 24;458(3):400-4. doi: 10.1016/s0014-5793(99)01073-x.

Abstract

The effect of delta9-tetrahydrocannabinol (THC), the major psycho-active component of marijuana, in human prostate cancer cells PC-3 was investigated. THC caused apoptosis in a dose-dependent manner. Morphological and biochemical changes induced by THC in prostate PC-3 cells shared the characteristics of an apoptotic phenomenon. First, loss of plasma membrane asymmetry determined by fluorescent anexin V binding. Second, presence of apoptotic bodies and nuclear fragmentation observed by DNA staining with 4',6-diamino-2-phenylindole (DAPI). Third, presence of typical 'ladder-patterned' DNA fragmentation. Central cannabinoid receptor expression was observed in PC-3 cells by immunofluorescence studies. However, several results indicated that the apoptotic effect was cannabinoid receptor-independent, such as lack of an effect of the potent cannabinoid agonist WIN 55,212-2, inability of cannabinoid antagonist AM 251 to prevent cellular death caused by THC and absence of an effect of pertussis toxin pre-treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism
  • Apoptosis / drug effects*
  • Benzoxazines
  • DNA Fragmentation
  • Dronabinol / pharmacology*
  • Fluorescent Antibody Technique
  • Humans
  • Indoles / metabolism
  • Male
  • Mitochondria / drug effects
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Pertussis Toxin
  • Piperidines / pharmacology
  • Prostatic Neoplasms
  • Protein Binding / drug effects
  • Pyrazoles / pharmacology
  • Receptors, Cannabinoid
  • Receptors, Drug / metabolism
  • Sphingosine / analogs & derivatives
  • Sphingosine / pharmacology
  • Time Factors
  • Tumor Cells, Cultured
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Annexin A5
  • Benzoxazines
  • Indoles
  • Morpholines
  • N-acetylsphingosine
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Virulence Factors, Bordetella
  • AM 251
  • DAPI
  • Win 55212-2
  • Dronabinol
  • Pertussis Toxin
  • Sphingosine