title: Old Drug Scaffold, New Activity: Thalidomide-Correlated Compounds Exert Different Effects on Breast Cancer Cell Growth and Progression.
abstract: Thalidomide was first used for relief of morning sickness in pregnant women and then withdrawn from the market because of its dramatic effects on normal fetal development. Over the last decades, it has been used successfully for the treatment of several pathologies, including cancer. Many analogues with improved activity have been synthesized and tested. Herein we report some effects on the growth and progression of MCF-7 and MDA-MB-231 breast cancer cells by a small series of thalidomide-correlated compounds, which are very effective at inducing cancer cell death by triggering TNFα-mediated apoptosis. The most active compounds are able to drastically reduce the migration of breast cancer cells by regulation of the two major proteins involved in epithelial-mesenchymal transition (EMT): vimentin and E-cadherin. Moreover, these compounds diminish the intracellular biosynthesis of vascular endothelial growth factor (VEGF), which is primarily involved in the promotion of angiogenesis, sustaining tumor progression. The multiple features of these compounds that act on various key points of the tumorigenesis process make them good candidates for preclinical studies.
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Iacopetta
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", 70126, Bari, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Carocci
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Sinicropi
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", 70126, Bari, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Catalano
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", 70126, Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lentini
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ceramella
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Rosita
authors.initials: R
authors.lastname: Curcio
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Caroleo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D013792:Thalidomide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; D013792:Thalidomide
keywords: TNFα; angiogenesis; antitumor activity; apoptosis; thalidomide