Open Access

ARTICLE

Tanshinone IIA protects intestinal epithelial cells from ferroptosis through the upregulation of GPX4 and SLC7A11

HAN WANG^1,2,#, YANG SUN^1,2,#, XIAOXU ZHANG^2,3, XIAOYING WANG⁴, YUJUN XIA^1,*, LISHENG WANG^1,2,*

1 School of Basic Medicine, Qingdao University, Qingdao, 266071, China
2 Laboratory of Molecular Diagnosis and Regenerative Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
3 Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
4 Beijing Institute of Radiation Medicine, Beijing, 100850, China

* Corresponding Authors: YUJUN XIA. Email: ; LISHENG WANG. Email:
# These authors contributed equally to this work

BIOCELL 2023, 47(5), 1107-1115. https://doi.org/10.32604/biocell.2023.027131

Received 15 October 2022; Accepted 16 January 2023; Issue published 10 April 2023

Abstract

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. The destruction of the intestinal epithelial barrier is one of the major pathological processes in IBD pathology. Growing evidence indicated that epithelial cell ferroptosis is linked to IBD and is considered a target process. Methods: RAS-selective lethal 3 (RSL3) was used to induce ferroptosis in intestinal epithelial cell line No. 6 (IEC-6) cells, and cell ferroptosis and the effects of tanshinone IIA (Tan IIA) were determined by cell counting kit-8 (CCK-8), reactive oxygen species (ROS) staining, Giemsa staining and transmission electron microscope (TEM). The cell viability of natural product library compounds was determined by CCK-8. The expression of ferroptosis-related genes were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Results: Treatment of IEC-6 cells results in the accumulation of ROS and typical morphological characteristics of ferroptosis. RSL3 treatment caused rapid cellular cytotoxicity which could be reversed by ferrostatin-1 (Fer-1) in IEC-6 cells. Natural product library screening revealed that Tan IIA is a potent inhibitor of IEC-6 cell ferroptosis. Tan IIA could significantly protect the RSL3-induced ferroptosis of IEC-6 cells. Furthermore, the ferroptosis suppressors, glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and miR-17-92 were found to be early response genes in RSL3-treated cells. Treatment of IEC-6 cells with Tan IIA resulted in upregulation of GPX4, SLC7A11, and miR-17-92. Conclusion: Our study demonstrated that Tan IIA protects IEC-6 cells from ferroptosis through the upregulation of GPX4, SLC7A11, and miR-17-92. The findings might provide a theoretical grounding for the future application of Tan IIA to treat or prevent IBD.

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