2. Academic Validation
  3. Dual ferroptosis induction in N2-TANs and TNBC cells via FTH1 targeting: A therapeutic strategy for triple-negative breast cancer

Dual ferroptosis induction in N2-TANs and TNBC cells via FTH1 targeting: A therapeutic strategy for triple-negative breast cancer

  • Cell Rep Med. 2025 Jan 21;6(1):101915. doi: 10.1016/j.xcrm.2024.101915.
Yichen Liu 1,  Qingyan Sun 2,  Jingwen Guo 2,  Li Yan 3,  Yue Yan 1,  Yiting Gong 1,  Jiayi Lin 1,  Hu Yuan 1,  Jinmei Jin 1,  Bei Wang 1,  Hongzhuan Chen 1,  Lijun Zhang 4,  Weidong Zhang 5,  Xin Luan 6
Affiliations

Affiliations

  • 1 Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 2 National Key Laboratory of Lead Druggability Research (Shanghai Institute of Pharmaceutical Industry Co. Ltd., China State Institute of Pharmaceutical Industry Co. Ltd.), Shanghai 200040, China.
  • 3 School of Pharmacy, Naval Medical University, Shanghai 200433, China.
  • 4 Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: zhanglijun0407@shutcm.edu.cn.
  • 5 Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; School of Pharmacy, Naval Medical University, Shanghai 200433, China; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. Electronic address: wdzhangy@hotmail.com.
  • 6 Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: luanxin@shutcm.edu.cn.
PMID: 39809268 DOI: 10.1016/j.xcrm.2024.101915
Abstract

Tumor-associated neutrophils (TANs) play a critical role in the progression and prognosis of triple-negative breast Cancer (TNBC), with N2-type TANs known for their pro-tumor characteristics. This study introduces CT-1, a derivative of cryptotanshinone that effectively suppresses TNBC growth while selectively reducing the proportion of N2-type TANs within tumor tissue. Notably, CT-1 induces simultaneous Ferroptosis in both N2-type TANs and TNBC cells, a dual mechanism that enhances its therapeutic efficacy. The study identifies ferritin heavy chain 1 (FTH1), a key protein in iron metabolism, as the direct target of CT-1. By targeting FTH1, CT-1 facilitates the interaction between NCOA4 and ferritin, triggering ferritinophagy-mediated Ferroptosis. These findings position CT-1 as a promising therapeutic agent, offering a strategy to combat TNBC by inducing Ferroptosis in both N2-type TANs and Cancer cells. This approach underscores the potential of FTH1 as a therapeutic target for treating TNBC.

Keywords

FTH1; N2-type tumor-associated neutrophils; TNBC; cryptotanshinone derivative; ferroptosis.

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