Curcumin Suppresses Tumorigenesis via Promoting SLC1A5-mediated Ferroptosis in Breast Cancer

Abstract

Background: Breast cancer is one of the most malignant tumors in the female. Previous studies confirmed that Curcumin, a kind of polyphenol compound extract from the Curcuma longa underground rhizome, inhibits the survival of cancer cells. However, the functional role and mechanism of curcumin in breast cancer remain unclear.Methods: The cell counting kit-8 (CCK-8) assay was performed to examine the effect of curcumin on cell viability in both MDA-MB-453 and MCF-7 cells. Determination of lipid reactive oxygen species (ROS) level, malondialdehyde (MDA) production, and intracellular Fe2+ level was used to evaluate the effect of curcumin on cell ferroptosis. The protein levels were determined by western blot. A xenograft tumor model was employed to verify the antitumorigenic effect of curcumin on breast cancer in vivo.Results: Curcumin treatment significantly suppressed breast cancer cell viability in a dose-dependent manner. Moreover, curcumin triggered ferroptosis by enhancing the levels of lipid ROS, lipid peroxidation end-product MDA accumulation, and intracellular Fe2+. Mechanistically, curcumin administration impeded tumor growth via upregulating solute carrier family 1 member 5 (SLC1A5)-mediated ferroptosis in breast cancer. In vivo experiments showed that curcumin could effectively hamper the growth of tumors without noticeable side effects.Conclusion: We demonstrated that curcumin exhibits anti-tumorigenesis activity in breast cancer by promoting SLC1A5-mediated ferroptosis, providing a potential therapeutic agent for the treatment of breast cancer.

Targeting of cancer cell death mechanisms by curcumin: Implications to cancer therapy

“…93 A similar study showed that upregulation of solute carrier family 1 member 5 (SLC1A5) in breast cancer cells has a role in the induction of ferroptosis and suppression of tumourigenesis. 94 In addition to breast cancer cells, the anticancer effect of curcumin through induction of ferroptosis has been observed in lung cancer cells. Treatment of two different lung cancer cell lines including A549 and H1299 cells confirmed the tumoursuppressive effect of curcumin through induction of ferroptosis.…”