# Polyunsaturated fatty acids supplementation and Lipocalin 2 blockade in preventing pancreatic cancer

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $157,500

## Abstract

Project summary:
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that lacks successful preventive measures
where the pro-inflammatory molecule lipocalin 2 (LCN2) is upregulated. Our laboratory showed that the tumor-
derived protein LCN2 is elevated in the blood and tumors of PDAC patients and that it promotes inflammation
in the tumor microenvironment (TME). Recently, it was suggested that LCN2 could inhibit ferroptosis due to its
iron binding properties. Ferroptosis is an iron dependent form of non-apoptotic cell death characterized by
excessive peroxidation of polyunsaturated fatty acids (PUFAs) catalyzed by iron in the cells. PUFA oxidation is
necessary for ferroptosis induction, but there is limited evidence on the potential of a PUFA supplementation to
induce cancer ferroptosis. To our knowledge, there are only a few in-vitro studies in other cancer types that
explore the potential of using PUFA supplementation to promote ferroptosis. PUFA supplementation studies
containing n-3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) are widely available and have shown
beneficial effects in health. Understanding whether PUFA supplementation could be used as a preventive
mechanism for PDAC development will lay the groundwork to develop efficient preventive strategies targeted
for PDAC high-risk individuals. We propose to fill these gaps in knowledge by 1) determining whether a PUFA
supplementation including DHA and EPA, will sensitize early pancreas cancer cells to ferroptosis and prevent
the development of PDAC; and 2) whether the effectiveness of this intervention will be enhanced by
modulating LCN2 levels. HYPOTHESIS: PUFA dietary supplementation in combination with LCN2 antibody
blockade will promote ferroptosis by increasing lipid peroxidation, and will prevent the formation of early lesions
of PDAC and progression of these lesions into cancer. In order to test this hypothesis, we aim to determine
whether a PUFA dietary intervention prevents tumor development by promoting ferroptosis and whether the
effect can be enhanced by decreasing LCN2 levels. IMPACT: Data from this study will inform us on whether a
PUFA supplementation could prevent PDAC by promoting ferroptosis, and whether LCN2 mediates ferroptosis
sensitivity. Our study will provide insights to guide new PDAC preventive strategies and dietary
supplementation guidelines for patients at risk of this disease.

## Key facts

- **NIH application ID:** 10510111
- **Project number:** 3R01CA223204-05S1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Zobeida Cruz-Monserrate
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $157,500
- **Award type:** 3
- **Project period:** 2018-07-19 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510111

## Citation

> US National Institutes of Health, RePORTER application 10510111, Polyunsaturated fatty acids supplementation and Lipocalin 2 blockade in preventing pancreatic cancer (3R01CA223204-05S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10510111. Licensed CC0.

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