Calycosin synergistically promotes ferroptosis in cervical cancer cells by inducing epithelial-mesenchymal transition
- 1College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China
- 2College of Basic Medical Sciences, Jiangsu Health Vocational College, Nanjing, Jiangsu 211800, P.R. China
Abstract
Cervical cancer treatment faces challenges from chemotherapy resistance. Inducing ferroptosis is a promising strategy. Calycosin (Cal), an active component of Astragalus membranaceus, exhibits antitumor activity, but its role in cervical cancer, particularly regarding epithelial-mesenchymal transition (EMT) and ferroptosis, remains unclear. Cell Counting Kit-8, colony formation and Transwell assays assessed Cal's effects on cell viability, migration and invasion. Ferroptosis was evaluated by detecting reactive oxygen species (ROS), malondialdehyde, glutathione and ferrous iron (Fe2+) levels, mitochondrial morphology and expression of ferroptosis-related proteins. EMT markers and signaling pathways (TGF-β/Smad and Hippo/YAP) were analyzed using western blot. TGF-β1 knockdown was used to investigate the functional link between EMT and ferroptosis in vitro and in vivo. Cal inhibited proliferation and induced ferroptosis in cervical cancer cells, evidenced by mitochondrial shrinkage, lipid peroxidation and altered glutathione peroxidase 4/solute carrier family 7 member 11/acyl-CoA synthetase long-chain family member 4 expression. However, Cal also promoted migration and invasion, upregulated mesenchymal markers, and activated TGF-β/Smad while inhibiting Hippo/YAP signaling. Importantly, TGF-β1 knockdown suppressed both Cal-induced EMT and ferroptosis, indicating a synergistic relationship. In vivo studies confirmed these findings, showing Cal inhibited primary tumor growth but promoted metastasis, effects attenuated by TGF-β1 knockdown. Cal exerts dual effects in cervical cancer: Inducing ferroptosis to inhibit growth while promoting EMT-associated metastasis via TGF-β/Smad and Hippo/YAP pathways. Crucially, Cal-induced EMT synergistically enhances ferroptosis sensitivity. These findings highlight the complex pharmacology of Cal and suggest that combining with EMT inhibitors may optimize its therapeutic potential while mitigating pro-metastatic risks.
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BibTeX
@article{zhang2026calycosin,
title = {{Calycosin synergistically promotes ferroptosis in cervical cancer cells by inducing epithelial-mesenchymal transition}},
author = {Lei Zhang and Qiuyi Shen and Jingyi Zhu and Ping Wang and Wanhong Wei and Jie Zhou},
journal = {Oncology Letters},
year = {2026},
month = oct,
doi = {10.3892/ol.2026.15912},
url = {https://europepmc.org/article/PMC/PMC13720401},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Calycosin synergistically promotes ferroptosis in cervical cancer cells by inducing epithelial-mesenchymal transition
AU - Lei Zhang
AU - Qiuyi Shen
AU - Jingyi Zhu
AU - Ping Wang
AU - Wanhong Wei
AU - Jie Zhou
PY - 2026
DA - 2026/10/19
JO - Oncology Letters
DO - 10.3892/ol.2026.15912
UR - https://europepmc.org/article/PMC/PMC13720401
AB - Cervical cancer treatment faces challenges from chemotherapy resistance. Inducing ferroptosis is a promising strategy. Calycosin (Cal), an active component of Astragalus membranaceus, exhibits antitumor activity, but its role in cervical cancer, particularly regarding epithelial-mesenchymal transition (EMT) and ferroptosis, remains unclear. Cell Counting Kit-8, colony formation and Transwell assays assessed Cal's effects on cell viability, migration and invasion. Ferroptosis was evaluated by detecting reactive oxygen species (ROS), malondialdehyde, glutathione and ferrous iron (Fe2+) levels, mitochondrial morphology and expression of ferroptosis-related proteins. EMT markers and signaling pathways (TGF-β/Smad and Hippo/YAP) were analyzed using western blot. TGF-β1 knockdown was used to investigate the functional link between EMT and ferroptosis in vitro and in vivo. Cal inhibited proliferation and induced ferroptosis in cervical cancer cells, evidenced by mitochondrial shrinkage, lipid peroxidation and altered glutathione peroxidase 4/solute carrier family 7 member 11/acyl-CoA synthetase long-chain family member 4 expression. However, Cal also promoted migration and invasion, upregulated mesenchymal markers, and activated TGF-β/Smad while inhibiting Hippo/YAP signaling. Importantly, TGF-β1 knockdown suppressed both Cal-induced EMT and ferroptosis, indicating a synergistic relationship. In vivo studies confirmed these findings, showing Cal inhibited primary tumor growth but promoted metastasis, effects attenuated by TGF-β1 knockdown. Cal exerts dual effects in cervical cancer: Inducing ferroptosis to inhibit growth while promoting EMT-associated metastasis via TGF-β/Smad and Hippo/YAP pathways. Crucially, Cal-induced EMT synergistically enhances ferroptosis sensitivity. These findings highlight the complex pharmacology of Cal and suggest that combining with EMT inhibitors may optimize its therapeutic potential while mitigating pro-metastatic risks.
SN - 1792-1074
SN - 1792-1082
ER -