1. Sanguinarine suppresses basal-like breast cancer growth through dihydrofolate reductase inhibition
- Author
-
Barbara Belletti, Maria Elexpuru Zabaleta, Augusto Amici, Valentina Gambini, Cristina Kalogris, Manuela Iezzi, Cristiano Lucci, Cristina Andreani, Chiara Garulli, Stefania Pucciarelli, Cristina Marchini, Lucia Pietrella, Caterina Bartolacci, Mara Giangrossi, and Martina Tilio
- Subjects
Programmed cell death ,Cell Survival ,Apoptosis ,Breast Neoplasms ,Mice, Inbred Strains ,Biochemistry ,Mice ,Necrosis ,Random Allocation ,chemistry.chemical_compound ,Cyclin D1 ,Downregulation and upregulation ,Cell Movement ,Cell Line, Tumor ,Dihydrofolate reductase ,Animals ,Humans ,Sanguinarine ,Viability assay ,STAT3 ,Neoplasms, Basal Cell ,Benzophenanthridines ,Pharmacology ,biology ,Isoquinolines ,Antineoplastic Agents, Phytogenic ,Molecular biology ,Neoplasm Proteins ,Tumor Burden ,Tetrahydrofolate Dehydrogenase ,Methotrexate ,chemistry ,Drug Resistance, Neoplasm ,biology.protein ,Cancer research ,Folic Acid Antagonists ,Female ,Neoplasm Transplantation - Abstract
Basal-like breast cancer (BLBC) remains a great challenge because of its clinically aggressive nature and lack of effective targeted therapy. We analyzed the potential anti-neoplastic effects of sanguinarine, a natural benzophenanthridine alkaloid, against BLBC cells. Sanguinarine treatment resulted in a reduction of cell migration, in a dose-dependent inhibition of cell viability and in the induction of cell death by apoptosis in both human (MDA-MB-231 cells) and mouse (A17 cells) in vitro models of BLBC. In vivo experiments demonstrated that oral administration of sanguinarine reduced the development and growth of A17 transplantable tumors in FVB syngeneic mice. Western blotting analysis revealed that suppression of BLBC growth by sanguinarine was correlated with a concurrent upregulation of p27 and downregulation of cyclin D1 and with the inhibition of STAT3 activation. In addition, we identified sanguinarine as a potent inhibitor of dihydrofolate reductase (DHFR), able to impair enzyme activity even in methotrexate resistant MDA-MB-231 cells. These results provide evidence that sanguinarine is a promising anticancer drug for the treatment of BLBC.
- Published
- 2014
- Full Text
- View/download PDF