Sanguinarine suppresses basal-like breast cancer growth through dihydrofolate reductase inhibition

Cristina Kalogris, Chiara Garulli, Lucia Pietrella, Valentina Gambini, Stefania Pucciarelli, Cristiano Lucci, Martina Tilio, Maria Elexpuru Zabaleta, Caterina Bartolacci, Cristina Andreani, Mara Giangrossi, Manuela Iezzi, Barbara Belletti, Cristina Marchini, Augusto Amici

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)226-234
Number of pages9
JournalBiochemical Pharmacology
Volume90
Issue number3
DOIs
Publication statusPublished - Aug 1 2014

Keywords

  • Apoptosis
  • Basal-like breast cancer
  • Dihydrofolate reductase (DHFR)
  • Mice
  • Sanguinarine
  • STAT3

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

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