title: The natural compound Alizarin as an osteotropic drug for the treatment of bone tumors.
abstract: Despite significant clinical improvements, conventional therapies for bone cancer treatment are limited by significant systemic toxicity and lack of specific targeting. In this study, we considered Alizarin, a natural hydroxyanthraquinone derived from madder root with high affinity to calcium and remarkable osteotropic features, as a novel approach for bone cancer treatment. Due to its antitumor properties, as demostrated in colon cancer cells, and to its tropism to bone, Alizarin may be an ideal drug to reduce bone tumor growth. We demonstrated that low dosages of Alizarin strongly inhibited the osteosarcoma (IC(50) for Saos-2, MG-63, and U-2 OS cells, 27.5, 29.0, and 69.9 µg/ml, respectively) and breast carcinoma (IC(50) for MDA-MB-231 cells, 62.1 µg/ml) cell proliferation in vitro. Importantly, Alizarin had a significantly lower inhibitory activity on normal cells (IC(50) for MSC, 828.6 µg/ml), thereby revealing a selective activity towards malignant cells. Furthermore, we found that Alizarin acted through the inhibition of ERK phosphorylation and cell cycle arrest in the S-phase. Finally, Alizarin significantly and strongly impaired both osteosarcoma and breast cancer tumorigenesis. Our results highlight a selective and effective inhibitory activity of Alizarin towards cancerous cells, laying the basis for further studies to investigate its application in bone cancer therapy.
authors.affiliation: Laboratory for Pathophysiology, Istituto Ortopedico Rizzoli, Bologna, Italy. caterina.fotia@ior.it
authors.forename: Caterina
authors.initials: C
authors.lastname: Fotia
authors.forename: Sofia
authors.initials: S
authors.lastname: Avnet
authors.forename: Donatella
authors.initials: D
authors.lastname: Granchi
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldini
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy*; D001943:Breast Neoplasms / Q000188:drug therapy; D002277:Carcinoma / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy*
chemical_list: D000880:Anthraquinones; C010078:alizarin