Norcantharidin impairs mammary cancer stem cells growth and in vivo tumor progression

DAMIAN E. BERARDI; GUIDO CICUTTIN; AGUSTINA TARUSELLI; STÉFANO M. CIRIGLIANO; ELISA D. BAL DE KIER JOFFÉ; ALEJANDRO J. URTREGER; LAURA B. TODARO

Cordoba

Congreso; LII Reunion Anual Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular; 2016

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

Triple-negative breast cancer (TNCB) is characterized by an abundance of treatment-resistant cancer stem cells (CSC). Norcantharidin (NCTD) is a synthetic demethylated small-molecule analog of the naturally occurring cantharidin isolated from blister beetles. Unlike the conventional chemotherapeutics, NCTD toxicity is higher to cancer cells than normal ones, making this molecule promising for cancer treatment. In this work, using 4T1 and Hs578t triple negative mammary cell lines we propose to: A) Study the effect of NCTD on the in vitro proliferation potential. B) Analyze the effect of NCTD on self-renewal and clonogenic capacity of 4T1 and Hs578t derived CSC. C) Evaluate the effect of NCTD on the in vivo tumor progression of 4T1 cells. We observed that NCTD significantly reduced 4T1 and Hs578t cell proliferation. Related to CSC derived from both mammary cell lines, NCTD impaired the clonogenic capacity as well as the renewal potential. Finally, we performed an in vivo assay, where 4T1 cells were orthotopically inoculated in BALB/c mice, and NCTD was i.p. inoculated twice a week (5 mg/kg). We could determine that NCTD significantly reduced tumor volume in vivo. Our data suggest that NCTD treatment reduces tumor progression both in vitro and in vivo, possibly thorough a direct effect on CSC biology.