Role of cysteinyl leukotriene receptor-1 antagonists in treatment of experimentally induced mammary tumor: Does montelukast modulate antitumor and immunosuppressant effects of doxorubicin?

It has been reported that a leukotriene (LT)-D-4 receptor (i.e. cysteinyl LT I receptor; CysLTIR) has an important role in carcinogenesis. The current study was carried out to assess the possible antitumor effects of montelukast (MON), a CysLTIR antagonist, in a mouse mammary carcinoma model, that is, a solid Ehrlich carcinoma (SEC). Effects of MON on tumor-induced immune dysfunction and the possibility that MON may modulate the antitumor and immunomodulatory effects of doxorubicin (DOX) were also studied. The effects in tumor-bearing hosts of several dosings with MON (10 mg/kg, per os), with and without the added presence of DOX (2 mg/kg, intraperitoneal), were investigated in vivo; end points evaluated included assessment of tumor volume, splenic lymphocyte profiles/functionality, tumor necrosis factor-a content, as well as apoptosis and expression of nuclear factor-kappa B (NF-kappa B) among the tumor cells. The data indicate that MON induced significant antitumor activity against the SEC. MON treatments also significantly mitigated both tumor- and DOX-induced declines in immune parameters assessed here. Moreover, MON led to decreased NF-kappa B nuclear expression and, in doing so, appeared to chemosensitize these tumor cells to DOX-induced apoptosis.