Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice

B Jansen; E Heere-Ress; H Schlagbauer-Wadl; J Halaschek-Wiener; S Waltering; I Moll; H Pehamberger; D Marciano; Y Kloog; K Wolff

doi:10.1007/s001099900052

Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice

J Mol Med (Berl). 1999 Nov;77(11):792-7. doi: 10.1007/s001099900052.

Authors

B Jansen¹, E Heere-Ress, H Schlagbauer-Wadl, J Halaschek-Wiener, S Waltering, I Moll, H Pehamberger, D Marciano, Y Kloog, K Wolff

Affiliation

¹ Department of Dermatology, University of Vienna, Austria.

PMID: 10619439
DOI: 10.1007/s001099900052

Abstract

Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of therapeutic strategies. We evaluated the antitumor activity of S-trans, trans-farnesylthiosalicylic acid (FTS), a new inhibitor of Ras signal transduction, in a newly established SCID mouse xenotransplantation model for human MCC (seven animals per group). FTS injected intraperitoneally at 5 mg/kg per day for 2 weeks up-regulated the tumor suppressor p53 and induced tumor cell apoptosis in established MCCs growing subcutaneously in SCID mice. These effects led to a statistically significant inhibition of MCC growth (P<0.002). The mean tumor weights following FTS or control treatment were 0.32+/-0.15 g and 1.08+/-0.29 g, respectively. There was no evidence of FTS related toxicity at the effective dose used. Our findings stress the notion that FTS may qualify as a novel and rational treatment approach for MCC and possibly for other tumors that rely on tyrosine kinase signaling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Apoptosis
Carcinoma, Merkel Cell / drug therapy*
Carcinoma, Merkel Cell / metabolism
Carcinoma, Merkel Cell / pathology
Cell Division / drug effects
Farnesol / administration & dosage
Farnesol / analogs & derivatives*
Farnesol / pharmacology
Farnesol / therapeutic use
Female
Humans
Injections, Intraperitoneal
Male
Mice
Mice, SCID
Proto-Oncogene Proteins p21(ras) / metabolism
Salicylates / administration & dosage
Salicylates / pharmacology
Salicylates / therapeutic use*
Skin Neoplasms / drug therapy*
Skin Neoplasms / metabolism
Skin Neoplasms / pathology
Statistics, Nonparametric
Transplantation, Heterologous
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / metabolism

Substances

Antineoplastic Agents
Salicylates
Tumor Suppressor Protein p53
farnesylthiosalicylic acid
Farnesol
HRAS protein, human
Proto-Oncogene Proteins p21(ras)