Abstract 2454: Vitamin D-mediated anti-cancer activity involves iron homeostatic balance disruption and oxidative stress induction in breast cancer

Background: Vitamin D deficiency has long been associated with increased risk of breast cancer (BC). Moreover, increased cellular iron content is emerging as a biomarker of BC metastasis. Although the connection between vitamin D and cellular iron content in BC remains ambiguous, recent studies have shown that vitamin D exerts some of its anti-cancer effects by modulating the expression of key iron regulatory genes (IRGs). Herein, we addressed the question of whether vitamin D signaling plays a role in cellular iron homeostasis and whether this has a effects on breast cancer cell survival and growth.

Experimental Methods: Bioinformatics analysis from publicly available transcriptomic data set has been utilized to profile the expression status of key IRGs in vitamin D-treated breast cancer cells. Additionally, hormonal-responsive (MCF-7) and triple negative (MDA-MB-231) BC cells were treated with 1α,25-dihydroxyvitamin D3 (calcitriol; the vitamin D active form) and evaluated for labile iron content, expression of IR proteins, oxidative stress, and cell survival.

Results and Discussions: Bioinformatics analysis revealed that several IRGs including hepcidin, ferroportin, ferritin and transferrin receptor as well as genes related to metabolic cellular stress are differentially expressed in BC cells. Vitamin D treatment resulted in cellular iron depletion and differentially affected the expression of key IR proteins. Moreover, vitamin D induced oxidative stress and altered the redox balance in treated cells by reducing catalase protein levels and increasing the expression of several stress-related markers including γ-H2AX, hypoxia-inducible factor 1 alpha and hemoxygenase 1. Consecutively, BC cell survival was significantly decreased in vitamin D-treated cells.

Conclusion: Collectively, data presented here demonstrate that vitamin D disrupts iron homeostasis, augments oxidative damage and reduces BC cell survival and growth.

Citation Format: Khuloud Bajbouj, Jasmin Shafarin, Lina Sahnoon, Abeer Al-Ali, Jibran Sualeh Muhammad, Salman Y. Guraya, Mawieh Hamad. Vitamin D-mediated anti-cancer activity involves iron homeostatic balance disruption and oxidative stress induction in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2454.