We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response.
- Authors
Koji Yamanoi; Jumpei Ogura; Eijiro Nakamura; Shinji Ito; Yuki Nakanishi; Toshi Menju; Kosuke Kawaguchi; Yuko Hosoe; Mana Taki; Ryusuke Murakami; Ken Yamaguchi; Junzo Hamanishi; Masaki Mandai
- Abstract
Objective: High-fat diets are implicated in the progression of cancer, but reports suggest that the impact varies depending on the type of fat, such as saturated and unsaturated fatty acids. Uncovering the role of fatty acids may help guide nutrition and provide dietary therapy for cancer patients. In this study, we investigated the effect of common long-chain fatty acids, stearic acid (SA) and oleic acid (OA), on ovarian cancer (OC). Methods: We used half maximal inhibitory concentration (IC50), a 72-hour proliferation assay, flow cytometry, and western blot to examine SA cytotoxicity and OA effects. Liquid chromatography/mass spectrometry (LC/MS) measured fatty acid concentrations in tumors. We inhibited SCD1, which converts SA to OA, using CAY10566 and analyzed tumor growth in human OC cell lines and patient-derived xenografts in mice on diets rich in SA or OA, combined with CAY10566. Results: SA showed significant cytotoxicity, increasing unfolded protein response (UPR) marker expression dose-dependently. CAY10566 heightened SA's cytotoxicity by boosting intracellular SA and reducing OA, diminishing IC50 to 20 μM (p<0.05). However, adding OA negated SA's increased cell toxicity and UPR marker expression. In mice, SA-rich diets with CAY10566 notably suppressed OC growth compared to normal diets, an effect OA-rich diets reversed. LC/MS confirmed higher SA levels in the SA group, and immunohistochemistry showed increased CHOP, gH2AX, and caspase-3 expression in the SA-rich with CAY10566 group, which OA-rich diets reduced. Conclusion: SA suppresses OC growth by inducing UPR, an effect OA can counteract. Modifying dietary fatty acid content could potentially influence OC tumor growth, highlighting diet's role in cancer.
- Subjects
UNFOLDED protein response; TUMOR growth; SATURATED fatty acids; UNSATURATED fatty acids; OLEIC acid; HEPATOCELLULAR carcinoma; OMEGA-6 fatty acids
- Publication
Journal of Gynecologic Oncology, 2024, Vol 35, p17
- ISSN
2005-0380
- Publication type
Article
- DOI
10.3802/jgo.2024.35.S2.O5