Antiproliferative and Pro-Apoptotic Effects of Tuber borchii Extracts on Human Colorectal Cancer Cells via p53-Dependent Pathway Activation

Background/Objectives: Colorectal cancer (CRC) is one of the most aggressive malignancies and has a very high mortality rate. Several studies have shown that obesity and hyperlipidemia are among the factors implicated in the onset of this disease. These factors can be modified through lifestyle changes, and diet plays a crucial role in this context. We evaluated the effects of Tuber borchii (T. borchii) fungal extracts based on experimental evidence showing that some truffles produce antioxidant, anti-inflammatory, and anticancer secondary metabolites. Methods: To this end, we treated human colorectal cancer cells (HCT 116) with various extracts of T. borchii at different time points and concentrations. Results and Conclusions: The results showed that the treatments caused a decrease in cell proliferation due to the induction of apoptotic cell death, as evidenced by FACS analyses. The apoptotic pathway was confirmed by the increase in the cleavage of Caspase 3 and Caspase 9. We then investigated the molecular mechanisms underlying cell death, finding increased nuclear localization of p53 and increased expression of its downstream pro-apoptotic genes, PUMA and NOXA. Among the upstream signaling events, we identify an increase in p-ERK1/2, a MAPK member involved in several antiproliferative/pro-apoptotic insults.