N-Ethyl-N-Nitrosourea Induced Leukaemia in a Mouse Model: Protective Effect of Icaritin via Inhibition of IL-6/JAK2/STAT3 Pathway Causes Apoptosis

Xinjun Hou; Yanhui Han; Abdurahman Hajinur Hirad; Abdullah A Alarfaj; Linxiang Liu

doi:10.2147/JIR.S441755

N-Ethyl-N-Nitrosourea Induced Leukaemia in a Mouse Model: Protective Effect of Icaritin via Inhibition of IL-6/JAK2/STAT3 Pathway Causes Apoptosis

J Inflamm Res. 2024 Feb 7:17:777-790. doi: 10.2147/JIR.S441755. eCollection 2024.

Authors

Xinjun Hou¹, Yanhui Han², Abdurahman Hajinur Hirad³, Abdullah A Alarfaj³, Linxiang Liu⁴

Affiliations

¹ Department of Traditional Chinese Medicine Hematology, Xin'an People's Hospital, Luoyang, Henan, 471000, People's Republic of China.
² Department of Internal Medicine of Traditional Chinese Medicine, Xin'an the Second People's Hospital, Luoyang, Henan, 471000, People's Republic of China.
³ Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
⁴ Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.

Abstract

Background: The present study aimed to investigate the protective effect of icaritin (ICT) on ENU-induced leukemia in male mice.

Methods: The mice received intraperitoneal injections of 80 mg/kg ENU twice a week for three months for induction of leukemia. Blood smears from these mice showed blast cells, confirming the presence of leukemia. After confirming leukemia, mice were divided into control, ENU-induced leukemia, and leukemia groups (10 mg/kg bw and 20 mg/kg bw) were treated with ICT for 35 days. Blood, spleen, and liver samples were collected for analysis. The expression of IL-6, JAK2, STAT3, as well as inflammatory, pro-apoptotic (Bax), and anti-apoptotic (Bcl-2) proteins were evaluated using qPCR, immunohistochemistry, and immunofluorescence techniques.

Results: The study found that ICT inhibited inflammation and the IL-6/JAK2/STAT3 pathway in ENU-induced mice. ICT treatment induced apoptosis in the spleen and liver by activating Bax and downregulating Bcl-2. The findings provide novel evidence that ICT acts as a dual inhibitor of IL-6/JAK2/STAT3 signaling, promoting apoptosis and playing an essential role in anti-leukemic activity.

Conclusion: These results suggest that ICT has potential as a therapeutic target for treating leukemia, offering a novel approach to leukemia treatment through inhibiting the IL-6/JAK2/STAT3 pathway and induction of apoptosis.

Keywords: ICT; IL-6/JAK2/STAT3; N-ethyl-n-nitrosourea; apoptosis; inflammation; leukaemia.

Grants and funding

The authors extend their appreciation to the Researchers Supporting Project number (RSP2024R98), King Saud University, Riyadh, Saudi Arabia for financial support.