title: The Immune System As a New Possible Cell Target for AFP 464 in a Spontaneous Mammary Cancer Mouse Model.
abstract: Aminoflavone (AFP 464, NSC 710464), an antitumor agent which recently entered phase II clinical trials, acts against estrogen-positive breast cancer (ER+). AFP 464, which has a unique mechanism of action by activating aryl hydrocarbon receptor (AhR) signaling pathway, decreased tumor size, and growth rate in the estrogen dependent, Tamoxifen-sensitive spontaneous M05 mouse model. Considering that AhR has recently emerged as a physiological regulator of the innate and adaptive immune responses, we investigated whether AFP 464 modulates the immune response in our mouse model. Studies on the effect of AFP 464 on the immune system were carried in BALB/c mice bearing M05 semi-differentiated mammary adenocarcinomas that express estrogen and progesterone receptors. Splenic cells and tumor inflammatory infiltrates were studied by cytometric analyses. The modulation of splenocytes cytotoxic activity by AFP 464 was also evaluated. We further investigated the effects of AFP 464 on peritoneal macrophages by evaluating metalloproteinase, arginase, and iNOS activities. We found that AFP 464 increased splenic cytotoxic activity, diminished the number of systemic and local Treg lymphocytes, and MDSCs, and induced a M1 phenotype in peritoneal macrophages of M05 tumor bearing mice. Therefore, we conclude that AFP 464 modulates immune response which collaborates with its anti-tumor activity. Our results place the immune system as a novel target for this anti-cancer agent to strengthen the rationale for its inclusion in breast cancer treatment regimens. J. Cell. Biochem. 118: 2841-2849, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Universidad de Buenos Aires, Instituto de Oncología "Ángel H. Roffo", Área Investigaciones, Ciudad de Buenos Aires, Argentina.|National Scientific Council (CONICET), CABA, CABA, Argentina.
authors.forename: Mariana A
authors.identifier: 0000-0002-6657-1290
authors.initials: MA
authors.lastname: Callero
authors.affiliation: Universidad de Buenos Aires, Instituto de Oncología "Ángel H. Roffo", Área Investigaciones, Ciudad de Buenos Aires, Argentina.|National Scientific Council (CONICET), CABA, CABA, Argentina.
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Rodriguez
authors.affiliation: Universidad de Buenos Aires, Instituto de Oncología "Ángel H. Roffo", Área Investigaciones, Ciudad de Buenos Aires, Argentina.
authors.forename: Aldana
authors.initials: A
authors.lastname: Sólimo
authors.affiliation: Universidad de Buenos Aires, Instituto de Oncología "Ángel H. Roffo", Área Investigaciones, Ciudad de Buenos Aires, Argentina.|National Scientific Council (CONICET), CABA, CABA, Argentina.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bal de Kier Joffé
authors.affiliation: Universidad de Buenos Aires, Instituto de Oncología "Ángel H. Roffo", Área Investigaciones, Ciudad de Buenos Aires, Argentina.|National Scientific Council (CONICET), CABA, CABA, Argentina.
authors.forename: Andrea I
authors.initials: AI
authors.lastname: Loaiza Perez
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; C413760:aminoflavone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: AFP 464; IMMUNE SYSTEM; MAMMARY CANCER