Botulinum toxin type A inhibits the growth of LNCaP human prostate cancer cells in vitro and in vivo

Prostate. 2009 Aug 1;69(11):1143-50. doi: 10.1002/pros.20958.

Abstract

Introduction and objective: Botulinum toxin type A (BTA) intraprostatic injection induces an improvement of urinary symptoms related to benign prostatic hypertrophy (BPH). Infra-clinical prostate cancer (PCa) foci and pre-neoplasic lesions occur concomitantly with BPH in a significant number of patients. The objective of this study was to address whether BTA influences the growth of prostate tumors.

Methods: Proliferation of PC-3 and LNCaP cell lines exposed or not to BTA (Botox) was assessed and compared. Presence of synaptic vesicle 2 (SV2) protein, the membrane receptor of BTA, was studied in both cell lines. After nude mice bearing LNCaP xenografts received intra-tumoral BTA or saline injection, tumor volume, serum PSA, histopathology and detection of apoptosis were comparatively assessed.

Results: BTA significantly reduced LNCaP cell proliferation and increased apoptosis in a dose-dependent manner but did not affect PC-3. The SV2 receptor was present in both cell lines at a ratio of 4:1 (LNCaP/PC-3). One unit of BTA resulted in a significantly lower growth rate and slower PSA progression over 28 days compare to controls. The tumors were morphologically similar. There were significantly more apoptotic cells compared to controls.

Conclusion: BTA inhibits the growth of LNCaP human PCa cells in vitro and in vivo. These findings indicate that intra-prostatic BTA injections to treat BPH are unlikely to promote the growth of co-existing infra-clinical PCa foci in men. A potential inhibitory effect of BTA on the growth of human PCa should be further studied.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Animals
  • Apoptosis / drug effects
  • Botulinum Toxins, Type A / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Nude
  • Nerve Tissue Proteins / metabolism
  • Neurotoxins / pharmacology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Transplantation, Heterologous

Substances

  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Neurotoxins
  • SV2A protein, human
  • Botulinum Toxins, Type A