Mangiferin inhibits chronic stress-induced tumor growth in colorectal liver metastases via WAVE2 signaling pathway

Yiming Tao; Xuefei Tian; Jia Luo; Hongyi Zhu; Yi Chu; Lei Pei

doi:10.1016/j.heliyon.2023.e13753

Mangiferin inhibits chronic stress-induced tumor growth in colorectal liver metastases via WAVE2 signaling pathway

Heliyon. 2023 Feb 15;9(3):e13753. doi: 10.1016/j.heliyon.2023.e13753. eCollection 2023 Mar.

Authors

Yiming Tao^{1

2}, Xuefei Tian³, Jia Luo⁴, Hongyi Zhu^{5

6}, Yi Chu^{5

6}, Lei Pei⁷

Affiliations

¹ Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
³ Department of Internal Medicine, College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China.
⁴ Department of Surgery, Hunan Cancer Hospital, Affiliated Tumor Hospital of Central South University, Changsha, Hunan, 410013, China.
⁵ Department of Gastroenterology, The Second Xiangya Hospital, Central South University, 410011, China.
⁶ Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, China.
⁷ Department of General Surgery, The Second Xiangya Hospital, Central South University, 410011, China.

Abstract

Background: Evidence indicates that chronic stress promotes progression of colorectal liver metastases (CLM). Mangiferin is the active chemical constituent of the rhizomes of Anemarrhena asphodeloides Bunge. Mangiferin (MGF) exerts anti-inflammatory, anti-proliferative, anti-angiogenic, anti-fibrotic and antioxidant effects in a variety of cancers. Its mechanism in chronic stress and tumor growth is still poorly understood.

Methods: To investigate the effects of MGF on the CLM and tumor-associated depression, activated hepatic stellate cells (a-HSCs), HT-29 CRC cells, were used in chronic unpredictable mild stress (CUMS) of tumor-bearing models. Potential antidepressant activity was determined by FST, TST, SIT and serum cytokine (IL-6, IL-18 and TNF-α) examination. Downstream signaling molecules were detected by Western blot, immunohistochemistry and fluorescence microscopy.

Results: CUMS induced depression behavior and depression-related cytokines and promoted tumor growth in CLM. MGF-treated mice significantly improved chronic stress behaviors by reducing depression-related cytokines. In addition, MGF treatment inhibits WAVE2 signaling pathway, leading to TGF-β1 induced HSC inhibition, thereby reducing depressive behavior and tumor growth in CLM.

Conclusion: MGF can alleviate CUMS induced tumor growth and the treatment of CLM patients with MGF may be beneficial.

Keywords: Chronic stress; Colorectal liver metastases; Mangiferin.