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Curcumin suppresses tumorigenesis by ferroptosis in breast cancer.

ABSTRACT: Breast cancer (BC) is one of the most common malignant tumors found in females. Previous studies have demonstrated that curcumin, which is a type of polyphenol compound extracted from Curcuma longa underground rhizome, is able to inhibit the survival of cancer cells. However, the functional role and mechanism of curcumin in BC are still unclear. The Cell Counting Kit-8 assay was performed to examine the effects of curcumin on cell viability in the BC cell lines MDA-MB-453 and MCF-7. The levels of lipid reactive oxygen species (ROS), malondialdehyde (MDA) production, and intracellular Fe2+ were determined to assess the effects of curcumin on cell ferroptosis. Western blot analysis was also carried out to detect the protein levels. Finally, the antitumorigenic effect of curcumin on BC was identified in a xenograft tumor model. In the present study, the results indicated that curcumin could dose-dependently suppress the viability of both MDA-MB-453 and MCF-7 cells. Further studies revealed that curcumin facilitated solute carrier family 1 member 5 (SLC1A5)-mediated ferroptosis in both MDA-MB-453 and MCF-7 cells by enhancing lipid ROS levels, lipid peroxidation end-product MDA accumulation, and intracellular Fe2+ levels. In vivo experiments demonstrated that curcumin could significantly hamper tumor growth. Collectively, the results demonstrated that curcumin exhibited antitumorigenic activity in BC by promoting SLC1A5-mediated ferroptosis, which suggests its use as a potential therapeutic agent for the treatment of BC.

SUBMITTER: Cao X

PROVIDER: S-EPMC8765616 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:NUDT21, an RNA binding protein, has been reported to play an important role in the regulation of multiple biological responses. Detection of NUDT21 expression may lead to the identification of a novel marker for breast cancer. Purpose:The aim of this study was to investigate the clinical significance and functional role of NUDT21 in breast cancer. Methods:The protein expression of NUDT21 was examined by immunohistochemistry (IHC) in 100 paraffin-embedded, archived breast cancer samples and 100 benign breast tissues. Then, the correlations between the NUDT21 expression and clinicopathologic characteristics and prognoses of the breast cancer patients were analyzed. In addition, the function of NUDT21 in breast cancer cell lines was detected by the methyl thiazolyl tetrazolium, colony formation and ?t?ranswell assays. Finally, mass spectrometry analysis and Western blotting were used to identify the proteins that interact directly with NUDT21. Results:IHC analysis revealed that the expression of NUDT21 was significantly lower in breast cancer tissues compared with benign breast disease tissues. The correlation analysis revealed that low expression of NUDT21 was positively correlated with tumor size, lymph node metastasis, and TNM stage. Also, Kaplan-Meier survival curves showed that patients with lower NUDT21 expression had shorter overall survival and relapse-free survival compared with higher NUDT21 expression. In addition, the knockdown of NUDT21 enhanced cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Consistently, the overexpression of NUDT21 inhibited cell proliferation, migration, invasion, and EMT. In addition, NUDT21 directly interacted with CPSF6 and negatively regulated its expression. Moreover, the knockdown of CPSF6 reversed NUDT21 expression-induced cancer cell migration and invasion. Conclusion:NUDT21 might play a tumor-suppressive role by inhibiting cell proliferation and invasion via the NUDT21/CPSF6 signaling pathway in breast cancer cells.

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Curcumin suppresses tumorigenesis by ferroptosis in breast cancer.

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