Effect of Aloysia polystachya in cancer stem cells of colorectal cancer

SOARES MACHADO M; PALMA A; PANELO L.C.; PAZ L.; ROSA, F D; LIRA, M C; AZURMENDI P; RUBIO M F; LENZ, GUIDO; URTREGER A; COSTAS M A

Congreso; AACR Annual Meeting 2020; 2020

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers andthe Cancer Stem Cells (CSC) are the responsible of CRC persistence. Aloysiapolystachya (AP) is an aromatic native plant of Verbenaceae family which iswidely distributed and consumed in infusions in subtropical regions of SouthAmerica. Its effects include diuretic, sedative, antispasmodic activities. We havepreviously demonstrated that AP extract has a cytotoxic effect in severalhuman tumor cell lines, including apoptosis. The aim of this work was toinvestigate the cytotoxic effects of AP in vitro and in vivo in a CRC model.Therefore, CRC cell lines CT26 (murine) and HCT116 (human), were stimulatedwith AP extract or vehicle, with or without 5-fluorouracyle (5-FURA) and thesurvival and CSC properties were determined. The survival was measured aftercrystal violet staining at 570nm and CSC phenotype was determined bymeasuring the plurytpotency markers (CD133, OCT4 and Nanog by PCR andIFI), colony formation by clonogenic assay and HOESCHT eflux capacity(chemotherapeutic drugs eflux via ABCG2-transporters). In vivo experimentsinvolved male BALB/c mice that were subcutaneously inoculated with murineCRC CT26 cell line. Once the tumor was detected, animals were treated twice aweek (days 14, 17, 21, 24 and 28) with an intraperitoneal injection with AP andthe sub-e􀃠ective dose of 5-FURA (5mg/kg). Normal animals, not inoculated withCT26 cells were also used as control for histological analysis.The tumor sizewas determined twice a week. After 30 days, the mice were sacri􀃕ced andnecropsied and the histopathology of tumors and the liver sections wasperformed by staining with hematoxylin and eosin. We found that AP extractdecreased significantly the expression level of pluripotency markers, thecolony formation and the eflux capacity of chemotherapeutic drugs respect tocontrol cells and increased the cell death induced by 5-FURA treatmentrespect to cells stimulated with 5-FURA alone (P