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.
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.


METHODS
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.


RESULTS
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.
Catalano
M G
MG
Department of Clinical Pathophysiology, University of Turin, Italy.
Costantino
L
L
Fortunati
N
N
Bosco
O
O
Pugliese
M
M
Boccuzzi
G
G
Berta
L
L
Frairia
R
R
D000622:Aminolevulinic Acid / Q000378:metabolism / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D019220:High-Energy Shock Waves; D006801:Humans; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology*; D010778:Photochemotherapy; D013964:Thyroid Neoplasms / Q000473:pathology / Q000628:therapy*
D000972:Antineoplastic Agents, Phytogenic; D000622:Aminolevulinic Acid; D017239:Paclitaxel