1. ¹Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels (ULB), Brussels, Belgium
2. ²Unibioscreen SA, Brussels, Belgium
3. ³Department of Neurosurgery, Erasmus University Hospital, ULB, Brussels, Belgium

Correspondence: Dr Robert Kiss, Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels, Campus de la Plaine CP205/1 – Boulevard du Triomphe, 1050 Brussels, Belgium. E-mail: rkiss@ulb.ac.be

Received 6 October 2006; Revised 13 February 2007; Accepted 7 March 2007; Published online 10 May 2007.

Abstract

The rapid increase in the incidence of malignant melanomas has not been associated with improved therapeutic options over the years. Indeed melanomas have proven resistant to apoptosis (type I programmed cell death (PCD)) and consequently to most chemotherapy and immunotherapy. It is believed that this resistance can be partly overcome by proautophagic drugs inducing type II (autophagy) PCD. Change at the genomic, transcriptional, and post-translational level of G-proteins and protein kinases, including Ras, plays an important role in the ability of melanomas to resist apoptosis. Ras transformation itself requires membrane anchorage and the overexpression of galectin-1 increases membrane-associated Ras. In this study, it has been found that decreasing galectin-1 expression in B16F10 mouse melanoma cells in vitro by means of an anti-galectin-1 small interfering RNA approach does not modify their sensitivity to type I and type II PCD. However, it does induce heat shock protein 70-mediated lysosomal membrane permeabilization, a process associated with cathepsin B release into the cytosol, which in turn is believed to sensitize the cells to the proautophagic effects of temozolomide when grafted in vivo. Furthermore, temozolomide when compared to the proapoptotic drug cisplatin, significantly increased the survival times of mice in the B16F10 melanoma model.