Hassan S.K.Mousa A.M.El-Sammad N.M.Abdel-Halim A.H.Khalil W.K.B.Elsayed E.A.Anwar N.Linscheid M.W.Moustafa E.S.Hashim A.N.Nawwar M.Department of BiochemistryNational Research CentreDokkiCairoEgypt; Department of Cell BiologyNational Research CentreDokkiCairoEgypt; Bioproducts Research ChairZoology DepartmentCollege of ScienceKing Saud UniversityRiyadhSaudi Arabia; Department of Chemistry of Natural and Microbial ProductsNational Research CentreDokkiCairoEgypt; Department of PathologyNational Cancer InstituteCairo UniversityCairoEgypt; Laboratory of Applied Analytical and Environmental ChemistryHumboldt-UniversityBerlinGermany; October University of Modern Sciences and Arts6th October CityEgypt; Department of Phytochemistry and Plant SystematicsNational Research CentreCairoEgypt2020-01-092020-01-09201922147500https://doi.org/10.1016/j.toxrep.2019.10.004PubMedIDhttps://t.ly/GggezScopusLung cancer has one of the highest mortality rates among various types of cancer and is the most frequent cancer in the world. The incidence of lung cancer is increasing rapidly, in parallel with an increased incidence of smoking. Effective chemoprevention may be an alternative strategy to control the incidence of lung cancer. Thus, the objective of current work was to ascertain the possible preventive and therapeutic efficacies of Cuphea ignea extract in a mouse model of lung tumorigenesis and its cytotoxicity toward the A549 human lung cancer cell line. Lung tumorigenesis was induced by the oral administration of benzo(a)pyrene (50 mg/kg b.w.) twice per week to Swiss albino mice for 4 weeks. Benzo(a)pyrene-treated mice were orally administered C. ignea (300 mg/kg body weight, 5 days/week) for 2 weeks before or 9 weeks after the first benzo(a)pyrene dose, for a total of 21 weeks. At the end of the administration period, various parameters were measured in the serum and lung tissues. The results revealed that the oral administration of benzo(a)pyrene resulted in increases in relative lung weight, serum levels of tumor markers (ADA, AHH, and LDH), and the inflammatory marker NF-?B, and a decreased total antioxidant capacity compared with the control. In addition, decreased levels of enzymatic and non-enzymatic antioxidants, with a concomitant increase in lipid peroxidation, metalloproteinases (MMP-2 and MMP-12), and the angiogenic marker VEGF were detected in lung tissues. Moreover, benzo(a)pyrene administration induced the upregulation of PKC?, COX-2, and Bcl-2 expression, with the downregulation of BAX and caspase-3 expression. C. ignea treatment alleviated all alterations in these parameters, which was further confirmed by the histopathological analysis of lung tissues. The findings of the current work provide the first verification of the preventive and therapeutic potentials of C. ignea extract against benzo(a)pyrene-induced lung tumorigenesis in mice. � 2019 The AuthorsEnglishOctober University for Modern Sciences and ArtsUniversity for Modern Sciences and ArtsMSA Universityجامعة أكتوبر للعلوم الحديثة والآدابBenzo(a)pyreneCuphea igneaLung tumorigenesisPlant phenolicsadenosine deaminaseantineoplastic agentbenzo[a]pyrenebeta actincaspase 3Cuphea ignea extractcyclooxygenase 2immunoglobulin enhancer binding proteinlactate dehydrogenasemacrophage elastaseplant extractprotein Baxprotein bcl 2tumor markerunclassified drugunspecific monooxygenasevasculotropinA-549 cell lineaerial plant partalbino mouseanimal cellanimal experimentanimal modelanimal tissueantineoplastic activityArticlebody weightcancer incidencecarbon nuclear magnetic resonancecarcinogenesiscell culturecell viability assaychemoprophylaxiscolumn chromatographycontrolled studycytotoxicityDNA fragmentationdrug induced diseaseelectrospray mass spectrometrygene expressionheteronuclear multiple bond correlationheteronuclear single quantum coherencehistopathologyIC50in vitro studyin vivo studylipid peroxidationliquid chromatography-mass spectrometrylung cancerlung parenchymalung weightmalemouseMTT assaynonhumanoxidative stresspaper chromatographypriority journalproton nuclear magnetic resonancereal time polymerase chain reactionsmokingthin layer chromatographyArticlehttps://doi.org/10.1016/j.toxrep.2019.10.004PubMedID