PMID- 34094899 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240402 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 11 DP - 2021 TI - Iron Regulates the Warburg Effect and Ferroptosis in Colorectal Cancer. PG - 614778 LID - 10.3389/fonc.2021.614778 [doi] LID - 614778 AB - Iron promotes the proliferation of cancer cells, but it also contributes to cell death. Here we explored whether iron could promote the Warburg effect of colorectal cancer (CRC) cells and suppress sensitivity to ferroptosis by inducing reactive oxygen species (ROS) and regulating nuclear factor erythroid 2-related factor 2 (NRF2). In this study, cell proliferation abilities were measured by CCK-8, EdU incorporation, and colony formation assays. Seahorse XF96 respirometry assays were used to detect the Warburg effect and the level of ROS was assess by DCFH-DA fluorescent probes. Results showed that iron exposure promoted the Warburg effect of CRC cells by inducing ROS and activating NRF2 both in vivo and in vitro. In addition, iron exposure also induced ferroptosis in CRC cells, but at the same time its inhibitory proteins SLC7A11 and GPX4 were also upregulated, indicating an enhanced resistance to ferroptosis. Our results revealed that iron can effectively promote tumorigenesis. Meanwhile, iron elimination or a low-iron diet might be valid therapeutic approaches for CRC. CI - Copyright (c) 2021 Yuan, Ni, Zhuge, Li and Li. FAU - Yuan, Yin AU - Yuan Y AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Ni, Shuo AU - Ni S AD - Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China. FAU - Zhuge, Aoxiang AU - Zhuge A AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. FAU - Li, Bo AU - Li B AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. AD - Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, China. FAU - Li, Lanjuan AU - Li L AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. AD - Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, China. LA - eng PT - Journal Article DEP - 20210518 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC8169994 OTO - NOTNLM OT - NRF2 OT - ROS OT - ferroptosis OT - iron OT - the Warburg effect COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/06/08 06:00 MHDA- 2021/06/08 06:01 PMCR- 2021/01/01 CRDT- 2021/06/07 06:03 PHST- 2020/10/07 00:00 [received] PHST- 2021/04/12 00:00 [accepted] PHST- 2021/06/07 06:03 [entrez] PHST- 2021/06/08 06:00 [pubmed] PHST- 2021/06/08 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2021.614778 [doi] PST - epublish SO - Front Oncol. 2021 May 18;11:614778. doi: 10.3389/fonc.2021.614778. eCollection 2021.