Anticancer effects and mechanisms of astragaloside‑IV (Review)

Abstract

Astragalus membranaceus Bunge is widely used in Traditional Chinese Medicine to treat various cancers. Astragaloside-IV (AS-IV) is one of the major compounds isolated from A. membranaceus Bunge and has been demonstrated to have antitumor effects by inhibiting cell proliferation, invasion and metastasis in various cancer types. Numerous studies have used in vitro cell culture and in vivo animal models of cancer to explore the antitumor activities of AS-IV.In the present study, the antitumor effects and mechanisms of AS-IV reported in studies recorded in the PubMed database were reviewed. First, the antitumor effects of AS-IV on proliferation, cell cycle, apoptosis, autophagy, invasion, migration, metastasis and epithelial-mesenchymal transition processes in cancer cells and the tumor microenvironment, including angiogenesis, tumor immunity and macrophage-related immune responses to cancer cells, were comprehensively discussed. Subsequently, the molecular mechanisms and related signaling pathways associated with antitumor effects of AS-IV as indicated by in vitro and in vivo studies were summarized, including the Wnt/AKT/GSK-3β (glycogen synthase kinase-3β)/β-catenin, TGF-β/PI3K/AKT/mTOR, PI3K/MAPK/mTOR, PI3K/AKT/NF-κB, Rac family small GTPase 1/RAS/MAPK/ERK, TNF-α/protein kinase C/ERK1/2-NF-κB and Tregs (T-regulatory cells)/IL-11/STAT3 signaling pathways. Of note, several novel mechanisms of Toll-like receptor 4 (TLR4)/NF-κB/STAT3, pSmad3C/3L, nuclear factor erythroid 2-related factor (NrF2)/heme oxygenase 1, circDLST/microRNA-489-3p/eukaryotic translation initiation factor 4A1 and macrophage-related high-mobility group box 1-TLR4 signaling pathways associated with the anticancer activity of AS-IV were also included. Finally, the limitations of current studies that must be addressed in future studies were pointed out to facilitate the establishment of AS-IV as a potent therapeutic drug in cancer treatment. Contents1. Introduction 2. Inhibitory effects of AS-IV on growth and proliferation of cancer cells 3. Inhibiting tumor growth by improving the TME, tumor immunity and immunotherapy and decreasing tumor angiogenesis 4. Antitumor mechanisms and related signaling pathways 5. Other novel anticancer mechanisms and related pathways 6. Conclusion and future perspectives

A review of natural products targeting tumor immune microenvironments for the treatment of lung cancer

“…Astragalus membranaceus Bunge, also known as “HuangQi”, is widely used to treat various cancers in Traditional Chinese medicine (TCM). AS-IV, a well-investigated and significant natural compound in TCM, has exhibited its anti-tumor properties by impeding the growth, invasion, and metastasis of tumor cells in multiple cancer types ( 93 ). TAMs are key regulators of the complex interplay between cancer and the TIME ( 94 ) and a significant therapeutic target in LC.…”

Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases

“…Astragaloside (3- O-β-D -xylopyranosyl- 6-O-β-D -glucopyranosyl-cycloastragenol) has a complex chemical structure consisting of a triterpenoid backbone with a cycloartane structure, which belongs to the saponin family. Astragaloside has been found to have a range of pharmacological activities, including antioxidant, anti-inflammatory, and immunomodulatory effects ( Zhou et al, 2023 ). Some meta-analyses focused on clinical and preclinical studies also indicate that astragaloside may offer potential treatment benefits for conditions including hepatic fibrosis, heart failure, neurological diseases, diabetes, and cancer ( Costa et al, 2019 ; Xiao et al, 2020 ; Zhou et al, 2020 ; Han et al, 2021 ; Li et al, 2023 ).…”

Epigenetic Signatures of Aging: A Comprehensive Study of Biomarker Discovery

“…been suggested as a way to potentially reverse some aspects of aging. Several compounds are being researched for their potential to activate telomerase, including astragalosides [106], huperzine A [107], cycloastragenol [108], and TA-65 [109]. Senolytic drugs target senescent cells, which are thought to contribute to aging and age-related diseases.…”