Abstract
Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment. Curcumin (CUR), a well-known cancer inhibitor, significantly inhibits the viability of breast cancer cells. Through transcriptomic analysis and flow cytometry experiments, it was found that after 48 hours of treatment of breast cancer cells at its half maximal inhibitory concentration (IC50), curcumin suppressed the viability of cancer cells via induction of ferroptotic death. Use of the ferroptosis inhibitor ferrostatin-1 and the iron chelator deferoxamine rescued cell death induced by curcumin. Furthermore, in subsequent cell validation experiments, the results showed that curcumin caused marked accumulation of intracellular iron, reactive oxygen species, lipid peroxides, and malondialdehyde, while glutathione levels were significantly downregulated. These changes are all manifestations of ferroptosis. Curcumin upregulates a variety of ferroptosis target genes related to redox regulation, especially heme oxygenase-1 (HO-1). Using the specific inhibitor zinc protoporphyrin 9 (ZnPP) to confirm the above experimental results showed that compared to the curcumin treatment group, treatment with ZnPP not only significantly improved cell viability but also reduced the accumulation of intracellular iron ions and other ferroptosis-related phenomena. Therefore, these data demonstrate that curcumin triggers the molecular and cytological characteristics of ferroptosis in breast cancer cells, and HO-1 promotes curcumin-induced ferroptosis.
Highlights
Breast cancer is the most common invasive cancer in women and the second most common cause of death [1]
The results of our current study suggest that curcumin triggers the molecular and cytological features of ferroptosis in breast cancer cells by upregulating heme oxygenase-1 (HO-1) and downregulating glutathione peroxidase 4 (GPX4)
It was obvious that ferroptosis occurred in response to curcumin treatment
Summary
Breast cancer is the most common invasive cancer in women and the second most common cause of death [1]. Approximately 2.1 million new breast cancer cases were diagnosed in 2018, accounting for one-quarter of cancer cases in women [2]. According to the North American Association of Central Cancer Registries (NAACCR) criteria, the breast cancer subtypes are defined as HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2- [3]. Fewer than 30% of women with metastatic triple negative breast cancer (TNBC) survive 5 years [5]. In addition to the known effective molecular targets of classical chemotherapy treatment, the search for new targets among natural drugs with extensive anticancer effects is expected to become a feasible strategy for the safe treatment of breast cancer [6]
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