Abstract 3822: Novel evidence for the role of the p53 signaling pathway in mediating the anticancer effects of aronia berry extract in colorectal cancer cells

Abstract

Abstract Background: The development of safe and effective novel agents remains a critical challenge for improving the prognosis of patients with unresectable colorectal cancer (CRC). Natural products containing polyphenols can be a good source of anti-cancer agents for their potential effect on multiple signaling pathways with anti-cancer effect. Due to its rich polyphenols content, Aronia berry extract (ABE) is gaining increased attention as an anti-cancer agent with its protective effect against cancer cells, including CRC, exerting potent antioxidant and antiproliferative effects. Thus, we hypothesized that ABE could be a novel complementary therapeutic option in patients with CRC by virtue of its ability to modulate multiple key cancer-related pathways. Methods: First, an MTT assay was performed to prove the antiproliferative effect of ABE in two CRC cells, SW480 and HCT116, and IC25 and IC50 of ABE in both CRC cells were identified. Next, the anti-cancer effects of ABE were examined by wound healing, colony formation, and invasion assays. Apoptosis studies were performed using the Muse Annexin V & Dead Cell Assay Kit on the muse cell analyzer. RNA-sequencing was performed to clarify the critical regulatory genes and pathways modulated by ABE by comparing genome-wide profiling between CRC cells with and without ABE treatment. Results: Results of the MTT assay revealed that ABE decreased the viability of both CRC cells, and the IC25 and IC50 of ABE were 80.0 µg/mL and 130.0 µg/mL for SW480 and 80.0 µg/mL and 140.0 µg/mL for HCT116. ABE inhibited proliferation, migration, cellular survival, and invasion of CRC cells and induced apoptosis in those cells (SW480 control vs. IC25: p<0.05, control vs. IC50: p<0.01, HCT116 control vs. IC25: p<0.01, control vs. IC50: p<0.01). After ABE treatment, the genome-wide transcriptomic analysis identified 439 differentially expressed genes (p<0.05 and |log2FC|>0.5) in both CRC cells. These differentially expressed genes were used for pathway analysis and some critical cancer-related pathways, including the p53 signaling pathway (p=0.005, fold enrichment 3.8), NF-kappa B signaling pathway (p=0.030, fold enrichment 2.7), Hippo signaling pathway (p=0.037, fold enrichment 2.2), and MAPK signaling pathway (p=0.011, fold enrichment 2.0), were detected as significantly activated or suppressed pathways. Conclusions: We have investigated the anti-cancerous effect of ABE in CRC cells and identified multiple critical cancer-related pathways modulated by ABE, with the p53 signaling pathway as the key mediator for growth suppressive anti-cancer efficacy of this naturally occurring phytochemical. Our findings provide evidence for the use of ABE as a safe and effective complementary and integrative medicine approach against CRC. Citation Format: Yoh Asahi, Keisuke Okuno, Caiming Xu, Aknobu Taketomi, Ajay Goel. Novel evidence for the role of the p53 signaling pathway in mediating the anticancer effects of aronia berry extract in colorectal cancer cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3822.