High energy shock waves activate 5'-aminolevulinic Acid and increase permeability to Paclitaxel: antitumor effects of a new combined treatment on anaplastic thyroid cancer cells

Thyroid. 2007 Feb;17(2):91-9. doi: 10.1089/thy.2006.0142.

Abstract

Objective: Multimodal treatments do not meaningfully improve survival of anaplastic thyroid cancer. Consequently, new effective therapeutic modalities are needed. The use of paclitaxel is under clinical investigation; it shows about a 50% response rate, but it is not able to alter the fatal outcome for patients with anaplastic carcinoma. High energy shock waves (HESW) have been shown to cause a transient increase in the permeability of cell membranes thus allowing higher intracellular drug concentrations. 5-Aminolevulinic acid (ALA) is used in the photodynamic therapy (PDT) of cancer, and HESW are under evaluation for their use as an activator in ALA-PDT.

Design: We investigated the effect of HESW produced by a piezoelectric generator on the sensitivity to paclitaxel and ALA treatments of two different anaplastic thyroid cancer cell lines (ARO and CAL-62). Cells, treated sequentially with ALA and paclitaxel were exposed to HESW; thereafter, cell viability and apoptosis induction were evaluated.

Main outcome: Combined exposure to ALA, paclitaxel, and shock waves resulted in a significant enhancement of cytotoxicity and induction of apoptosis in thyroid cancer cells with respect to cells treated with paclitaxel alone.

Conclusions: These preliminary data suggest the possibility of using HESW and ALA in combination with paclitaxel as a promising new therapy in the treatment of anaplastic thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / metabolism
  • Aminolevulinic Acid / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma / pathology
  • Carcinoma / therapy*
  • Cell Line, Tumor
  • Cell Membrane Permeability*
  • Cell Survival / drug effects
  • Combined Modality Therapy
  • High-Energy Shock Waves*
  • Humans
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / pharmacology*
  • Photochemotherapy*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / therapy*

Substances

  • Antineoplastic Agents, Phytogenic
  • Aminolevulinic Acid
  • Paclitaxel