Combined therapy with chloroquine and propranolol for colorectal and triple negative breast cancers treatment

ANSELMINO, LUCIANO; BAGLIONI, MARÍA VIRGINIA; CHAPO, GUSTAVO; MENACHO-MÁRQUEZ, MAURICIO

Congreso; Congreso Nacional de Ciencia y Tecnología de Animales de Laboratorio; 2021

Drug repositioning refers to new uses for existing drugs outside the scope of their original medical indications. This approach fastens the process of drug development allowing finding effective drugs with reduced side effects and lower costs. Colorectal cancer (CRC) is often diagnosed at advanced stages, when the probability of chemotherapy resistance is higher. Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, highly metastatic and difficult to treat. For both tumor types, available treatments are generally associated to severe side effects. In our work, we explored the effect of combining chloroquine (CQ) and propranolol (Prop), two repositioned drugs, in both tumor types. We demonstrate by in vitro experiments that CQ+Prop treatment affects viability, apoptosis and migratory potential of CRC and TNBC cells. To corroborate our data in in vivo models, CRC and TNBC cells were subcutaneously injected into the right flank of 8-week-old female mice (BALB/c or immunodeficient mice according to the cell type; CICUAL authorization for the project “"Nuevos enfoques terapéuticos para el tratamiento del cáncer”,Facultad de Ciencias Médicas, UNR)". Animals were fed with commercial diet, water ad libitum, and kept in12h light/dark cycles at the CIPReB facilities. Tumor volume was periodically measured with a caliper. When tumors reached 80 mm3 animals were arbitrarily separated and treated by adding CQ and/or Prop to the drinking water (65 and 7mg/kg/day respectively, N=4-6/group). Body weight and tumor growth were periodically monitored. When tumors reached the maximum size ethically allowed, animals were sacrificed by overexposure to CO2. Tumor, spleen and lungs were removed for histological analysis. The results indicated that CQ+Prop treated animals carrying CRC showed lower tumor growth kinetics than the control group.