Abstract
PURPOSE: American Indian and Alaska Native (AI/AN) populations experience significant cancer disparities, with 2% higher incidence but 18% higher mortality compared to non-Hispanic Whites. Low socioeconomic status is linked to late diagnosis of several gastrointestinal cancers (including colorectal and pancreatic), with insurance status being a minor factor. Reducing oncogenic infections, improving access to quality cancer care, and increasing support for tribal healthcare is crucial for addressing the disproportionate cancer burden in AI/AN communities.
DESIGN METHODS: We investigated Cd exposure on the development of Pancreatic ductal adenocarcinoma (PDAC). Indoleamine 2,3-dioxygenase (IDO), is a potential therapeutic target in cancer (immune checkpoint). Cadmium (Cd) exposure has been implicated in pancreatic cancer is a common environmental pollutant and is found in high concentrations in cigarette smoke. This study investigates the individual and combined effects of IDO inhibition (1-methyl-D-tryptophan) and Cd exposure on pancreatic cell lines.
RESULTS: Cd exposure upregulated SIRT1 and mTOR expression, suggesting a pro-cancer effect in control cells, effects that were not reversed by IDO inhibition. Combining 1-MT and Cd further increased mTOR and RAPTOR expression in PDAC cells. Cd exposure increased MMP-2 and -9 expression in both cell lines, enzymes involved in extracellular matrix degradation and cancer progression.
DISCUSSION/CONCLUSION: IDO inhibition and Cd exposure differentially affected normal and cancerous pancreatic cells. IDO inhibition may increase the tumorigenic properties of Cd and considering the potential for Cd exposure in the AI/AN population, these findings have implications for developing IDO-targeted therapies in the context of environmental toxicant exposures. Further studies are needed to understand the mechanisms and impact of tryptophan metabolism modulation on pancreatic cancer development.
DESIGN METHODS: We investigated Cd exposure on the development of Pancreatic ductal adenocarcinoma (PDAC). Indoleamine 2,3-dioxygenase (IDO), is a potential therapeutic target in cancer (immune checkpoint). Cadmium (Cd) exposure has been implicated in pancreatic cancer is a common environmental pollutant and is found in high concentrations in cigarette smoke. This study investigates the individual and combined effects of IDO inhibition (1-methyl-D-tryptophan) and Cd exposure on pancreatic cell lines.
RESULTS: Cd exposure upregulated SIRT1 and mTOR expression, suggesting a pro-cancer effect in control cells, effects that were not reversed by IDO inhibition. Combining 1-MT and Cd further increased mTOR and RAPTOR expression in PDAC cells. Cd exposure increased MMP-2 and -9 expression in both cell lines, enzymes involved in extracellular matrix degradation and cancer progression.
DISCUSSION/CONCLUSION: IDO inhibition and Cd exposure differentially affected normal and cancerous pancreatic cells. IDO inhibition may increase the tumorigenic properties of Cd and considering the potential for Cd exposure in the AI/AN population, these findings have implications for developing IDO-targeted therapies in the context of environmental toxicant exposures. Further studies are needed to understand the mechanisms and impact of tryptophan metabolism modulation on pancreatic cancer development.
Original language | American English |
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Pages | 64 |
State | Published - 13 Sep 2024 |
Event | 2024 Symposium on Tribal and Rural Innovations in Disparities and Equity for Health - Oklahoma State University College of Osteopathic Medicine at the Cherokee Nation, Tahlequah, United States Duration: 13 Sep 2024 → 13 Sep 2024 |
Conference
Conference | 2024 Symposium on Tribal and Rural Innovations in Disparities and Equity for Health |
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Abbreviated title | STRIDE 2024 |
Country/Territory | United States |
City | Tahlequah |
Period | 13/09/24 → 13/09/24 |