title: Umbelliprenin induced production of IFN-γ and TNF-α, and reduced IL-10, IL-4, Foxp3 and TGF-β in a mouse model of lung cancer.
abstract: Umbelliprenin is a member of the 7-prenyloxycoumarins with potential therapeutic properties such as cytotoxic effects on various cancer cells. The present study investigates the effect of umbelliprenin on predominance of Th1 and Th2 responses in Lewis lung cancer (LLC) mouse model. The cytotoxic effect of umbelliprenin was explored on LLC cells and mouse splenocytes by MTT assay. Mice into which LLC had been transplanted were treated with umbelliprenin on alternate days, at 2.5 mg/200 µl intraperitoneally. Foxp3, TNF-α and TGF-β mRNA expressions were assessed in tumor and lung tissues of LLC mice. In addition, IL-10, IFN-γ and IL-4 levels were determined in sera and also in splenocyte culture supernatants at the presence of tumor cell lysate (10 µg/ml) and Con A (3 µg/ml) after 72 h. Results showed the cytotoxic effects of umbelliprenin on LLC cells (IC₅₀ = 51.6 ± 5.4 µM) while no adverse effect was seen at this concentration on normal splenocytes. TNF-α mRNA expression in both lung and tumor tissues was increased. However, Foxp3 and TGF-β expressions were decreased in tumor tissues. Serum level of IFN-γ was elevated in the umbelliprenin treated cancerous mice compared to the control group while IL-10 and IL-4 secretions were reduced. Tumor size was also decreased in umbelliprenin treated group. In summary, umbelliprenin has shown a partially Th1 bias with a reduction of regulatory immune response. Although the mechanism behind this action is not known, it is speculated that upon changing the Th1/Th2 balance in favour of Th1, umbelliprenin induces its antitumor activity.
authors: Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences , Shiraz , Iran .
authors: Narges
authors: N
authors: Khaghanzadeh
authors: Afshin
authors: A
authors: Samiei
authors: Mohammad
authors: M
authors: Ramezani
authors: Zahra
authors: Z
authors: Mojtahedi
authors: Massood
authors: M
authors: Hosseinzadeh
authors: Abbas
authors: A
authors: Ghaderi
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D014468:Umbelliferones; D016753:Interleukin-10; D007371:Interferon-gamma; C003744:umbelliprenin