Colorectal cancer (CRC) is the third most frequent cancer type in both males and females, with about 35% of patients being diagnosed in stage IV metastatic disease. Despite advancements in treatment, life expectancy in patients with metastatic disease is still not satisfying. Due to frequent drug resistance during conventional and targeted cancer treatments, the development and testing of multi-target therapies is an important research field. Medicinal mushrooms specific isolated compounds as well as complex extract mixtures have been studied in depth, and many mushroom species have been proven to be non-toxic multi-target inhibitors of specific oncogenic pathways, as well as potent immunomodulators. In this study, we have performed a tandem mass tags qualitative and quantitative proteomic analyses of CT26.WT colon cancer tumor tissues from Balb/c mice treated with the studied medicinal mushroom extract mixture, with or without 5-fluorouracil. Besides significantly improved survival, obtained results reveal that Agarikon.1 alone, and in combination with 5-fluorouracil exert their anticancer effects by affecting several fundamental processes important in CRC progression. Bioinformatic analysis of up- and downregulated proteins revealed that ribosomal biogenesis and translation is downregulated in treatment groups, while the unfolded protein response (UPR), lipid metabolism and tricarboxylic acid cycle (TCA) are upregulated. Moreover, we found that many known clinical biomarkers and protein clusters important in CRC progression and prognosis are affected, which are a good basis for an expanded translational study of the herein presented treatment.
Keywords: cancer metabolism; colorectal cancer; combination therapy; medicinal mushrooms; multi-target; tandem mass tags proteomics; translation; unfolded protein response.
Copyright © 2020 Jakopovic, Horvatić, Klobučar, Gelemanović, Grbčić, Oršolić, Jakopovich and Kraljević Pavelić.