Abstract 6331: Prevention of lung cancer growth by an edible mushroom-derived p-terphenyl antioxidant, Vialinin-A

Lung cancer remains the leading cause of cancer-related deaths in the United States, surpassing the combined fatalities from colon, breast, and prostate cancer. In 2024, approximately 234,580 individuals were diagnosed with lung cancer, with projections indicating an increase in 2025. A history of smoking, both first and secondhand, the use of other combustible tobacco products, and hereditary risk factors have been strongly associated with lung cancer. Environmental exposures to radon, asbestos, arsenic, air pollution, and other occupational exposures exacerbate the likelihood of developing the disease. Novel treatment approaches are required to improve outcomes in lung cancer prognosis. Vialinin-A, a ubiquitin-specific peptidase inhibitor derived from Chinese edible mushrooms, T. terrestris and T. vialis, has potent antioxidant and anti-inflammatory properties. However, its potential anti-carcinogenic effects remain unexplored. Therefore, we hypothesize that Vialinin-A, with its potent anti-oxidative and anti-inflammatory effects, could prevent lung cancer growth. Human Non-Small Cell Lung Cancer (NSCLC) cell lines (A549) were used to investigate the potential chemopreventive role of Vialinin-A on lung cancer. An MTT assay was conducted to evaluate EGF-induced cell viability without or with Vialinin-A. The expression of pro-, anti-inflammatory, and apoptotic proteins was then assessed via multiplex antibody arrays. Mitochondrial reactive oxygen species (ROS) and a scratch array were then used to calculate cell migration. Cell death was observed using a live and death assay. Our results suggest that Vialinin-A could prevent EGF-induced lung cancer growth in a dose- and time-dependent manner. The expression of apoptotic proteins such as Catalase, Cleaved Caspase-3, cIAP-1, Claspin, SMAC/Diablo, and Clusterin was significantly upregulated in A549 cells treated with EGF+Vialinin-A. EGF-induced cell migration and invasion were prevented with Vialinin-A treatment. Vialinin-A also decreased the EGF-induced ROS and elevated caspase-3 levels. Thus, our data suggests that by increasing the caspase-3-mediated apoptotic pathway, Vialinin-A could prevent lung cancer growth and migration. Next, we will examine how Vialinin-A prevents lung cancer growth using nude mice xenograft models. Citation Format: Neha Ratna, Aleeza Namit, Kota A. Ramana. Prevention of lung cancer growth by an edible mushroom-derived p-terphenyl antioxidant, Vialinin-A [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6331.