Regulation of activity of cathepsins B, L, and D in murine lymphosarcoma model at a combined treatment with cyclophosphamide and yeast polysaccharide Tatyana A. Khalikova a , Svetlana Ya. Zhanaeva a , Tatyana A. Korolenko a , Vassilij I. Kaledin b , Grigorij Kogan c, * a Institute of Physiology, Siberian Branch of Russian Academy of Medical Sciences, 630117 Novosibirsk, Russia b Institute of Cytology and Genetics, Russian Academy of Sciences, 630090 Novosibirsk, Russia c Institute of Chemistry, Center of Excellence CEDEBIPO, Slovak Academy of Sciences, Dubravska cesta 9, 845 38 Bratislava, Slovakia Received 20 September 2004; received in revised form 19 October 2004; accepted 20 October 2004 Abstract Changes in the activity of cysteine (cathepsins B and L) and aspartyl (cathepsin D) proteases were investigated at the development of susceptible and resistant variants of murine lymphosarcoma (LS). It has been demonstrated that the variant resistant to the cyclophosphamide treatment is characterized by a lower activity of all three cathepsins in the tumor tissue. Application of a higher dose of cyclophosphamide led to a more pronounced increase of the studied enzymatic activity in mice with a resistant variant of LS, than in those with a susceptible one. Administration of a yeast polysaccharide derivative - sulfoethyl glucan - enhanced therapeutic effect of cyclophosphamide in mice with both variants of LS, while the most efficient dose was found to be that of 10 mg/kg body mass. In the intact mice, usage of both cyclophosphamide and sulfoethyl glucan led to a similar increase of the cathepsins activity in liver and spleen. q 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Cathepsins B, L, and D; Murine Lymphosarcoma; Yeast glucan 1. Introduction Cysteine proteases, i.e. cathepsins B and L, as well as aspartyl protease cathepsin D are involved in the development of malignant neoplastic processes in humans [1]. Secretion of the cathepsins B and L by tumor cells results in degradation of the extracellular matrix and in the lysis of basal membrane, which are indispensable prerequisites for tumor progression. Ability of tumor cells to secrete proteases correlates directly with their invasive and metastatic potential [2]. Enhanced expression and increased content and activity of the cathepsins B, L, and D were observed at the human mammary carcinoma, cancers of lungs, stomach, colon, and at melanoma [3]. At the experimental studies of the antitumor therapy of 0304-3835/$ - see front matter q 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.canlet.2004.10.028 Cancer Letters 223 (2005) 77–83 www.elsevier.com/locate/canlet * Corresponding author. Tel.: C421 2 5941 0274; fax: C421 2 5941 0222. E-mail address: grigorij.kogan@savba.sk (G. Kogan).