Anti-cancer role of Deflamin in colorectal cancer

Objectives: We have previously identified deflamin, an oligomeric protein isolated from the white lupine seeds (Lupinus albus), with anti-MMPs and anti-inflammatory properties. Given the involvement of MMPs and inflammation in the carcinogenesis process, in this work we sought to explore deflamin’s role in colorectal cancer development and progression. Material and Methods: In this work, we made use of colorectal cancer cell lines HT-29, HCT116, and SW480 to perform proliferation, apoptosis, migration and invasion assays. Zebrafish xenotransplant models were further used as a in vivo model of tumorigenesis. Results: We found that deflamin exerts an inhibitory effect on tumor growth and metastasis formation, contributing to increased tumor apoptosis in the xenotransplanted zebrafish larvae model. Furthermore, deflamin resulted not only in a significant reduction in MMP-2 and MMP-9 activity but also in impaired cancer cell migration and invasion in vitro. Using the xenograft zebrafish model, we observed that deflamin inhibits collagen degradation and angiogenesis in the tumor microenvironment in vivo. Conclusion: Overall, our results unravel the nutraceutical potential of deflamin in colorectal cancer treatment. Keywords: Deflamin, Colorectal cancer, MMP-2, MMP-9. Funding: This work was supported by national funds from Fundação para a Ciência e a Tecnologia (Lisbon, Portugal) through the research unit UID/AGR/04129/2020 (LEAF), Project PTDC/BAA-AGR/28608/2017 and Project PTDC/OCE-ETA/4836/2021.