All-Trans Retinoic Acid and Lapatinib combined treatment impair growth and cell cycle progression of breast cancer stem cells

AGUSTINA TARUSELLI; ANDRES BECHIS; LIZETH ARIZA BAREÑO; MARIA J. COSTA; DAMIAN DELBART; ALEJANDRO J. URTREGER; LAURA B. TODARO

Mar del Plata

Congreso; LXIV Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Sociedad Argentina de Investigación Clínica (SAIC)

Cancer stem cells (CSC) are resistant to both chemotherapy and radiotherapies and are also considered as the metastasis seed. Previously, we have demonstrated that CSC derived from HER2 negative breast cancer cells overexpress HER2. In order to validate a novel therapeutic strategy against the tumor stem component, analyzed the effect of ATRA and Lapatinib treatments on growth and cell cycle distribution of primary mammospheres derived from 4T1, HCC-70 and MCF-7 cell lines, that do not overexpress HER2.Primary mammospheres were treated for 96 h with Lapatinib 1 uM (for 4T1 and HCC-70 cells) and 5uM for MCF-7, combined or not with ATRA 1uM. No effect on mammospheres growth could be detected after these treatments in MCF7cells. Moreover, Lapatinib treatment increased HCC-70 mammospheres growth, while ATRA reduced this property in 4T1 mammospheres. However, the combined treatment, not only reduced CSC diameter but also induced cell death in both cell lines. Finally, we studied by flow cytometry, the effect of the above-mentioned treatments on cell cycle distribution. We found that Lapatinib and ATRA combined treatment induced cell arrest at G0/G1 phase after 48 h (4T1) and 72 h (MCF-7) of treatment.In the present work we have demonstrated that ATRA and Lapatinib combined treatment can successfully reduce breast CSC growth and induce cell cycle, providing in vitro evidences for the potential use of the combined treatment in HER2 negative mammary tumors.