Amurubicinol-induced eotaxin-3 expression in human NCI-H69 small cell lung carcinoma cells.
We previously demonstrated the doxorubicin-induced expression of urokinase-type plasminogen activator (uPA), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha in human RC-K8 lymphoma cells and NCI-H69 small cell lung carcinoma cells in which reactive oxygen species might be involved. Amurubicin hydrochloride (AMR), a novel derivative drug of doxorubicin, was recently introduced to clinical practice for treatment of lung cancer in Japan. Therefore, we investigated the effects of AMR on the expression of uPA and chemokines in NCI-H69 cells. AMR and its active form, amurubicinol hydrochloride (AMROH), both induced the expression of uPA, IL-8 and MCP-1 in H69 cells in a dose-dependent manner. When the cultured supernatant obtained from AMR-treated H69 cells was subcutaneously injected into rabbits, migration of a significant number of eosinophils was observed around the injected site. Antigen levels of eotaxin-3, a major migration-factor of eosinophils, were increased in AMROH-treated cells in parallel with the mRNA levels. The induction was observed below the clinically achievable concentration of AMR or AMROH. Thus, the simultaneous induction of uPA, IL-8, MCP-1 and eotaxin-3 may play a role in the pharmacological action of AMR through induction of the interaction between proinflammatory cells and lung carcinoma cells.
Niiya
Masami
M
Department of Medicine II, Faculty of Medicine, Okayama University Medical School, Okayama 700-8558, Japan. niiya7@yahoo.co.jp
Niiya
Kenji
K
Shibakura
Misako
M
Asaumi
Noboru
N
Yoshida
Chikamasa
C
Tanimoto
Mitsune
M
D000818:Animals; D018943:Anthracyclines / Q000494:pharmacology*; D015152:Blotting, Northern; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
D018943:Anthracyclines; C111835:CCL2 protein, human; C120429:CCL26 protein, human; D018932:Chemokine CCL2; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D012333:RNA, Messenger; C116173:amrubicinol; C055866:amrubicin; D014568:Urokinase-Type Plasminogen Activator