Cholangiocarcinoma (CCA) is a rare and highly aggressive malignancy which arises from the epithelial cells of the liver (intrahepatic) or the biliary duct (extrahepatic). Late diagnosis and pathophysiological heterogeneity are linked to poor prognosis, caused by limited effective targeted therapies, and resistance to conventional treatments. This highlights the urgent need for novel therapeutic strategies and more predictive in vitro models able to accelerate preclinical research. In this context, natural compounds such as Curcumin, a polyphenol derived from Curcuma longa, has drown attentions due to its reported antiproliferative, anti-inflammatory, and pro-apoptotic effects properties in different cancer models. This thesis aimed to study the antitumor efficacy of curcumin on extrahepatic CCA cell line, (i.e., TFK1) using both traditional 2D monolayer and 3D matrix-embedded culture systems.