ArticleCell death & disease2014
SBF-1 exerts strong anticervical cancer effect through inducing endoplasmic reticulum stress-associated cell death via targeting sarco/endoplasmic reticulum Ca(2+)-ATPase 2.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Trial
- UPR/ATF4/Noxa pathway overactivation through SERCA2 inhibition or ONC201 treatment combined with ABT-737 triggers apoptosis in chemoresistant ovarian cancer cells and patient-derived tumor organoids.Cell death & disease · 2026Article
- Glioma-Immune crosstalk in the tumor microenvironment: mechanistic insights and therapeutic translation.Medical oncology (Northwood, London, England) · 2026Review
- Identification and mechanistic exploration of VEGFA and CALML3 as calcium channel-related prognostic genes in cervical cancer.Discover oncology · 2026Article
- Variable roles of miRNA- and apoptosis-linked genes in invasive breast cancer: expression patterns, clinicopathological associations, and prognostic significance.Molecular biology reports · 2025Article
- Targeting SERCA2 in Anti-Tumor Drug Discovery.Current drug targets · 2025Review
- Independent organelle and organelle-organelle interactions: essential mechanisms for malignant gynecological cancer cell survival.Frontiers in immunology · 2024Review
- Diabetic cardiomyopathy: The role of microRNAs and long non-coding RNAs.Frontiers in endocrinology · 2023Review
- Highly expressed SERCA2 triggers tumor cell autophagy and is a druggable vulnerability in triple-negative breast cancer.Acta pharmaceutica Sinica. B · 2022Article
- Recent Developments on the Roles of Calcium Signals and Potential Therapy Targets in Cervical Cancer.Cells · 2022Review
- Selective targeting of the androgen receptor-DNA binding domain by the novel antiandrogen SBF-1 and inhibition of the growth of prostate cancer cells.Investigational new drugs · 2021Article
- Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines.Frontiers in oncology · 2021Article
- The effect of iron on the expression levels of calcium related gene in cisplatin resistant epithelial ovarian cancer cells.Exploration of targeted anti-tumor therapy · 2021Article
- SBF-1 inhibits contact hypersensitivity in mice through down-regulation of T-cell-mediated responses.BMC pharmacology & toxicology · 2019Article
- Discovery of SBF1 as an allosteric inhibitor targeting the PIF-pocket of 3-phosphoinositide-dependent protein kinase-1.Journal of molecular modeling · 2019Article
- Endoplasmic reticulum stress induced by an ethanol extract of Coicis semen in Chang liver cells.BMC complementary and alternative medicine · 2018Article
- Asymmetric dimethylarginine downregulates sarco/endoplasmic reticulum calcium‑ATPase 3 and induces endoplasmic reticulum stress in human umbilical vein endothelial cells.Molecular medicine reports · 2017Article
- KCNMA1 cooperating with PTK2 is a novel tumor suppressor in gastric cancer and is associated with disease outcome.Molecular cancer · 2017Article
- Endoplasmic Reticulum-Mitochondria Calcium Communication and the Regulation of Mitochondrial Metabolism in Cancer: A Novel Potential Target.Frontiers in oncology · 2017Review
- Regulation of Endoplasmic Reticulum-Mitochondria CaFrontiers in oncology · 2017Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cervical cancer is one of the most common carcinomas in the genital system. In the present study, we report that SBF-1, a synthetic steroidal glycoside, has a strong antigrowth activity against human cervical cancer cells in vitro and in vivo. SBF-1 suppressed the growth, migration and colony formation of HeLa cells. In addition, severe endoplasmic reticulum (ER) stress was triggered by SBF-1, and 4-phenyl-butyric acid, a chemical chaperone, partially reversed SBF-1-induced cell death. To uncover the target protein of SBF-1, the compound was labeled with biotin. The biotin-labeled SBF-1 bound to sarco/ER Ca(2+)-ATPase 2 (SERCA2) and colocalized with SERCA2 in HeLa cells. Moreover, SBF-1 inhibited SERCA activity, depleted ER Ca2+ and increased cytosolic Ca2+ levels. 1,2-Bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, a chelator of Ca2+, partially blocked SBF-1-induced ER stress and growth inhibition. Importantly, knockdown of SERCA2 increased the sensitivity of HeLa cells to SBF-1-induced ER stress and cell death, whereas overexpression of SERCA2 decreased this sensitivity. Furthermore, SBF-1 induced growth suppression and apoptosis in HeLa xenografts, which is closely related to the induction of ER stress and inhibition of SERCA activity. Finally, SERCA2 expression was elevated in human cervical cancer tissues (n=299) and lymph node metastasis (n=8), as compared with normal cervix tissues (n=23), with a positive correlation with clinical stages. In all, these results suggest that SBF-1 disrupts Ca2+ homeostasis and causes ER stress-associated cell death through directly binding to SERCA2 and inhibiting SERCA activity. Our findings also indicate that SERCA2 is a potential therapeutic target for human cervical cancer.
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