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)-D4 receptor (i.e. cysteinyl LT1 receptor; CysLT1R) has an important role in carcinogenesis. The current study was carried out to assess the possible antitumor effects of montelukast (MON), a CysLT1R 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-α content, as well as apoptosis and expression of nuclear factor-κB (NF-κB) 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-κB nuclear expression and, in doing so, appeared to chemosensitize these tumor cells to DOX-induced apoptosis.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Alaa El-Din E
Ael-D
El-Sisi
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Samia S
SS
Sokar
Department of Molecular Biology, Genetic Engineering and Biotechnology Institute, Minoufiya University, Minoufiya, Egypt.
Tarek A
TA
Salem
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt sally_risha@yahoo.com.
Sally E
SE
Abu Risha
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003521:Cyclopropanes; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D018077:Receptors, Leukotriene / Q000235:genetics / Q000378:metabolism*; D013440:Sulfides; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000085:Acetates; D000970:Antineoplastic Agents; D003521:Cyclopropanes; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D020024:Leukotriene Antagonists; D016328:NF-kappa B; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; C083169:leukotriene D4 receptor; C093875:montelukast
Mammary tumor; NF-κB; doxorubicin; immunity; montelukast