en Toxicology Toxicology پژوهشي Research <div><strong>Introduction:</strong> Chemotherapy was known as a potential approach for colon cancer therapy. Polymer-based nanocarriers prolong the circulation time of chemotherapeutic drugs, therefore anti-tumor drugs can passively accumulate in the malignant tumor position through the improved permeability and retention effect. The aim of the present study was to investigate anticancer potency of biodegradable and pH-sensitive nano-encapsulated Hydroxytyrosol in HT-29 cancer cell line and the potential molecular mechanism of action of Hydroxytyrosol.<br> <strong>Materials and Methods:</strong> The poly lactide-co-glycolide-co-polyacrylic acid (PLGA-co-PAA) nano-encapsulated Hydroxytyrosol was synthesized, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed to evaluate the anti-proliferative and anti-tumor effects of both free and nano-encapsulated Hydroxytyrosol. The relative expression of colorectal cancer associated-1 (COCA1) gene was investigated by quantitative Real-Time PCR (qRT-PCR).<br> <strong>Results:</strong> We observed that free and nano-encapsulated Hydroxytyrosol significantly decreased the viability of HT-29 cancer cells. Moreover, the cytotoxic effect of nano-encapsulated Hydroxytyrosol on HT-29 cancer cells was significantly more than that of free Hydroxytyrosol. Also, the <em>COLCA1</em> gene expression was up-regulated significantly in HT-29 cancer cells treated with either free or nano-encapsulated Hydroxytyrosol.<br> <strong>Conclusion: </strong>Generally, we showed that the anticancer potency of Hydroxytyrosol was significantly increased by a biodegradable and pH-sensitive nanoparticle. However, further studies on animal models seem necessary.</div> Colorectal cancer, PLGA-PAA copolymer, Hydroxytrylosol, COLCA1 gene 41 48 http://jbrms.medilam.ac.ir/browse.php?a_code=A-10-500-1&slc_lang=en&sid=1 Masoud Heidari haidarymasoud2@gmail.com 10031947532846007790 10031947532846007790 No Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Mohammadali Hosseinpourfeizi m.hosseinpourfeizi 10031947532846007791 10031947532846007791 No Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Nasrin Seyyed Sani seyyedsani.nasrin@yahoo.com 10031947532846007792 10031947532846007792 No Department of Genetic, Tabriz Branch, Islamic Azad University, Tabriz, Iran Narges Dastmalchi narges.bastmalchi@gmail.com 10031947532846007793 10031947532846007793 No Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Mohammad Saeid Moradzadeh Tehrani m.saeidmoradzadeh@gmail.com 10031947532846007794 10031947532846007794 No Department of Molecular Biology, Islamic Azad University, University in Arsanjan, Iran Morteza Soleyman-Nejad soleymannejad@yahoo.com 10031947532846007795 10031947532846007795 No Ariagene Medical Genetics Laboratory, Mahmoudnejad Ave, Qom, Iran Reza Safaralizadeh safaralizadeh@tabrizu.ac.ir 10031947532846007796 10031947532846007796 Yes Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran