Tetrahydrocurcumin regulates the tumor immune microenvironment to inhibit breast cancer proliferation and metastasis via the CYP1A1/NF-κB signaling pathway

Cancer Cell International

Research

Bao Chen¹  Yuan Tian²  Jing Zeng²  Ping Chen²  Ying Dai²  Xue Chen²  Hua Hua²  Junning Zhao³  Anqi Zeng³  Lu Hao⁴  Xinyue Yu⁵ 

[1] School of Pharmacy, Southwest Medical University, 646000, Luzhou, Sichuan, China;Sichuan Academy of Traditional Chinese Medicine, 610041, Chengdu, Sichuan, China;Sichuan Institute for Translational Chinese Medicine, 610041, Chengdu, Sichuan, China;Sichuan Academy of Traditional Chinese Medicine, 610041, Chengdu, Sichuan, China;Sichuan Institute for Translational Chinese Medicine, 610041, Chengdu, Sichuan, China;West China School of Pharmacy, Sichuan University, 610041, Chengdu, Sichuan, China;Sichuan Institute for Translational Chinese Medicine, 610041, Chengdu, Sichuan, China;West China School of Pharmacy, Sichuan University, 610041, Chengdu, Sichuan, China;

关键词: Tetrahydrocurcumin;    Tumor immune microenvironment;    Breast cancer;    Proliferation;    Metastasis;    CYP1A1;    NF-κB;   

DOI  :  10.1186/s12935-023-02850-9

 received in 2022-08-12, accepted in 2023-01-06,  发布年份 2023

来源: Springer

【 摘 要 】

The NF-κB signaling pathway is overactivated in tumor cells, and the activation of the NF-κB signaling pathway releases a large number of inflammatory factors, which enhance tumor immunosuppression and promote tumor metastasis. The cytochrome P450 (CYP450) system consists of important metabolic enzymes present in different tissues and progressive tumors, which may lead to changes in the pharmacological action of drugs in inflammatory diseases such as tumors. In this study, the anticancer effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on breast cancer cells and the underlying mechanism were investigated. Result showed that THC selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner. Moreover, THC-induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species (ROS) induction. In addition, THC could affect the CYP450 enzyme metabolic pathway and inhibit the expression of CYP1A1 and activation of the NF-κB pathway, thereby inhibiting the migration and invasion of breast cancer cells. Furthermore, after overexpression of CYP1A1, the inhibitory effects of THC on the proliferation, metastasis, and induction of apoptosis in breast cancer cells were weakened. The knockdown of CYP1A1 significantly enhanced the inhibitory effect of THC on the proliferation, metastasis, and apoptosis induction of breast cancer cells. Notably, THC exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MCF-7 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Collectively, these results showed that TH could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the CYP1A1/NF-κB signaling pathway, indicating that THC serves as a potential candidate drug for the treatment of breast cancer.

【 授权许可】

CC BY   
© The Author(s) 2023

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