ArticleFrontiers in pharmacology2021
Sini San Inhibits Chronic Psychological Stress-Induced Breast Cancer Stemness by Suppressing Cortisol-Mediated GRP78 Activation.
Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review.Molecular medicine (Cambridge, Mass.) · 2023Pooled it
- Chronic stress and cancer progression through neuro‑endocrine‑immune networks (Review).Oncology reports · 2026Review
- Si Ni Powder enhances chemotherapy efficacy in sleep-deprived breast cancer via modulation of the tumor microenvironment.Translational cancer research · 2026Article
- Clinical efficacy and multi-omics analysis of Si-Ni-San for depression treatment in breast cancer patients: a randomized, double-blind, placebo-controlled, crossover trial.Chinese medicine · 2026Article
- TPM-like manipulations exerted an antidepressant effect and regulated amino acid metabolism and GHR/IGF-1 pathway in the liver in adolescent female CUMS rats.Frontiers in physiology · 2026Article
- Chronic stress: a fourth etiology in tumorigenesis?Molecular cancer · 2025Review
- Molecular mechanisms and clinical value of the correlation between depression and cancer.Medical oncology (Northwood, London, England) · 2025Review
- Multi-target Mechanisms of Si-Ni-San on Anxious Insomnia: An Example of Network-pharmacology and Molecular Docking Analysis.Current medicinal chemistry · 2025Article
- Chronic Psychological Stress Activates TRP/TAM/CXCL1 Signaling to Promote Breast Cancer Adipocyte Lipolysis via KEAP1 mResearch (Washington, D.C.) · 2025Article
- Chaihu Longgu Muli Decoction inhibits chronic stress-induced lung cancer epithelial-mesenchymal transition process by suppressing Rap1/ERK signal pathway.Frontiers in pharmacology · 2025Article
- Network pharmacology to explore the mechanism of traditional Chinese medicine in the treatment of ground glass nodules.Journal of thoracic disease · 2024Article
- Integrated analyses for identification of a three-gene signature associated with Chaihu Shugan San formula for hepatocellular carcinoma treatment.Journal of cellular and molecular medicine · 2024Article
- Sini San ameliorates lipid metabolism in hyperprolactinemia rat with liver-depression.Current research in food science · 2024Article
- The therapeutic effect of traditional Chinese medicine on breast cancer through modulation of the Wnt/β-catenin signaling pathway.Frontiers in pharmacology · 2024Review
- Clinical implications of forkhead box M1, cyclooxygenase-2World journal of clinical cases · 2023Article
- Review
- Cell surface GRP78: a potential mechanism of therapeutic resistant tumors.Cancer cell international · 2023Review
- Chronic psychological stress promotes breast cancer pre-metastatic niche formation by mobilizing splenic MDSCs via TAM/CXCL1 signaling.Journal of experimental & clinical cancer research : CR · 2023Article
- Chronic stress in solid tumor development: from mechanisms to interventions.Journal of biomedical science · 2023Review
- Traditional Chinese Medicine for Breast Cancer: A Review.Breast cancer (Dove Medical Press) · 2023Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic psychological stress is closely correlated with breast cancer growth and metastasis. Sini San (SNS) formula is a classical prescription for relieving depression-related symptoms in traditional Chinese medicine (TCM). Current researches have suggested that chronic psychological stress is closely correlated with cancer stem cells (CSCs) and endoplasmic reticulum (ER) stress. This study aimed to investigate the effects of chronic psychological stress on ER stress-mediated breast cancer stemness and the therapeutic implication of SNS. Chronic psychological stress promoted lung metastasis in 4T1 breast tumor-bearing mice and increased the stem cell-like populations and stemness-related gene expression. Meanwhile, GRP78, a marker of ER stress, was significantly increased in the breast tumors and lung metastases under chronic psychological stress. As a biochemical hallmark of chronic psychological stress, cortisol dramatically enhanced the stem cell-like populations and mammospheres formation by activating GRP78 transcriptionally. However, GRP78 inhibitors or shRNA attenuated the stemness enhancement mediated by cortisol. Similarly, SNS inhibited chronic psychological stress-induced lung metastasis and stemness of breast cancer cells, as well as reversed cortisol-induced stem cell-like populations and mammospheres formation by attenuating GRP78 expression. Co-localization and co-immunoprecipitation experiments showed that SNS interrupted the interaction between GRP78 and LRP5 on the cell surface, thus inhibiting the Wnt/β-catenin signaling of breast CSCs. Altogether, this study not only uncovers the biological influence and molecular mechanism of chronic psychological stress on breast CSCs but also highlights SNS as a promising strategy for relieving GRP78-induced breast cancer stemness
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