Extract from Aloysia polystachya Induces the Cell Death of Colorectal Cancer Stem Cells

Abstract

Cancer stem cells (CSCs) are an important player in the resistance of cancers to therapy. In this work, we determined the flavonoids composition and biological action of Aloysia polystachya (AP) extracts in colorectal cancer. The chemical characterization of extracts was performed by HPLC. Assays of cytotoxicity, apoptosis, migration and invasion, metalloproteases activity, clonogenic growth, tumorspheres formation, Hoechts efflux, pluripotency marker expression and sensitization to chemotherapeutic drugs were performed in vitro in human HCT116 and murine CT26 colorectal cancer cells. The AP toxicity and effect in tumor growth administered alone or in combination with 5- Fluorouracile was analyzed in vivo, including histopathological studies. We found that AP extracts induced in vitro the apoptosis of colorectal cancer cell lines decreasing the CSC proportion. Moreover, they were capable to kill 5-Fluorouracile resistant side population cells. At not toxic doses in vivo, AP extracts inhibited tumor growth. Regarding the ability to reduce the CSC population, AP extracts deserves to be investigated as a useful therapy for colorectal cancer treatment.

Disclosure Statement

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Additional information

Funding

This work has been supported by grants from CONICET [PIP 11220150100118CO], National Institute of Cancer [2016–2018] and National Agency for Scientific and Technological Promotion [PICT 1424, PBID 2014].

Notes on contributors

Mileni Soares Machado

Mileni Soares Machado involved in all the experiments, in vitro and in vivo. Alejandra Palma cooperated with all the in vitro assays and figures preparing. Laura Panelo contributed to all the assays for cancer stem cells characterization. Leonardo Paz involved in histopathological studies-in vivo results interpretation. Francisco Rosa contributed to Western blots and curves of cytotoxicity. Maria C. Lira involved in extracts preparation and characterization and also in statistical analysis of in vitro and in vivo assays. Pablo Azurmendi involved in PCR assays-writing and edition of the manuscript. Maria F. Rubio involved in intellectual cooperation for experiment designs and data interpretation and in Figures preparation. Guido Lenz involved in designs of chemosensitivity experiments and also in manuscript revision and writing. Alejandro J. Urtreger contributed to design and performing in vivo experiments and data interpretation. Mónica A. Costas is the Director of the team and the mentor of the project.