Targeting ER Stress with Saikosaponin A to Overcome Resistance under Radiation in Gastric Cancer Cells

Saikosaponin A is a triterpene saponin and a potentially bioactive compound derived from Bupleurum falcatum L. However, the molecular mechanisms and effects of saikosaponin A in gastric cancer remain unknown. In the present study, I evaluated the effects of saikosaponin A on cell death and endoplasmic reticulum stress via calcium and reactive oxygen species release. Targeting reactive oxygen species with diphenyleneiodonium and N-acetylcysteine inhibited cell death and protein kinase RNA-like ER kinase signaling pathway by down-regulating Nox4 and inducing glucose-regulated protein 78 exosomes. Furthermore, saikosaponin A caused a synergistic inhibitory effect of the epithelial mesenchymal transition phenomenon, indicating the reversible phenotype modulation by epithelial cells under radiation exposure in radiation-resistant gastric cancer cells. These results suggest that saikosaponin A-mediated calcium and reactive oxygen species-induced endoplasmic reticulum stress overcome radio-resistance and induce cell death under radiation in gastric cancer cells. Therefore, saikosaponin A in combination with radiation may be a potential strategy for gastric cancer therapy.

• Publication year

  2023

• Venue

  International Journal of Molecular Sciences

• Publication date

  2023-03-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.3390/ijms24065661PMID 36982736PMCID 10052548
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A guide to understanding endoplasmic reticulum stress in metabolic disorders

  2021cited by this paper
• Exosomes derived from endoplasmic reticulum-stressed liver cancer cells enhance the expression of cytokines in macrophages via the STAT3 signaling pathway

  2020cited by this paper
• The Role of Endoplasmic Reticulum Stress in Cell Survival and Death.

  2020cited by this paper
• Study on the Anticancer Effect of an Astragaloside- and Chlorogenic Acid-Containing Herbal Medicine (RLT-03) in Breast Cancer

  2020cited by this paper
• Herbal Active Ingredients: An Emerging Potential for the Prevention and Treatment of Papillary Thyroid Carcinoma

  2020cited by this paper
• Absence of detectable effect of radiotherapy and chemotherapy for breast cancer on the presence of low voltage areas in patients receiving left atrial catheter ablation

  2020cited by this paper
• Saikosaponin D inhibits proliferation and induces apoptosis of non-small cell lung cancer cells by inhibiting the STAT3 pathway

  2020cited by this paper
• A Novel Salicylanilide Derivative Induces Autophagy Cell Death in Castration-Resistant Prostate Cancer via ER Stress-Activated PERK Signaling Pathway

  2019cited by this paper
• Chemotherapy Resistance Explained through Endoplasmic Reticulum Stress-Dependent Signaling

  2019cited by this paper
• The Effects and Mechanisms by which Saikosaponin-D Enhances the Sensitivity of Human Non-small Cell Lung Cancer Cells to Gefitinib

  2019cited by this paper
• The Role of Saikosaponins in Therapeutic Strategies for Age-Related Diseases

  2018cited by this paper
• Epidemiology of gastric cancer: global trends, risk factors and prevention

  2018cited by this paper
• PERK Regulates Glioblastoma Sensitivity to ER Stress Although Promoting Radiation Resistance

  2018cited by this paper
• Saikosaponin A, an active glycoside from Radix bupleuri, reverses P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cells and HepG2/ADM cells

  2017cited by this paper
• Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells

  2017cited by this paper
• Saikosaponin-d suppresses cell growth in renal cell carcinoma through EGFR/p38 signaling pathway.

  2017cited by this paper
• Saikosaponin-d, a calcium mobilizing agent, sensitizes chemoresistant ovarian cancer cells to cisplatin-induced apoptosis by facilitating mitochondrial fission and G2/M arrest

  2017influential reference
• Saikosaponin a Induces Apoptosis through Mitochondria-Dependent Pathway in Hepatic Stellate Cells.

  2017cited by this paper
• Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

  2016cited by this paper
• ER Stress-Mediated Signaling: Action Potential and Ca2+ as Key Players

  2016cited by this paper
• Saikosaponin‑d inhibits proliferation of DU145 human prostate cancer cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase.

  2014cited by this paper
• Saikosaponin-d inhibits proliferation of human undifferentiated thyroid carcinoma cells through induction of apoptosis and cell cycle arrest.

  2014cited by this paper
• Saikosaponin-d, a novel SERCA inhibitor, induces autophagic cell death in apoptosis-defective cells

  2013cited by this paper
• Saikosaponin-d increases the radiosensitivity of smmc-7721 hepatocellular carcinoma cells by adjusting the g0/g1 and g2/m checkpoints of the cell cycle

  2013cited by this paper
• ER stress-induced cell death mechanisms.

  2013cited by this paper
• Efficacy of combination treatment modalities for intermediate and advanced hepatocellular carcinoma: intra-arterial therapies, sorafenib and novel small molecules.

  2013cited by this paper
• Therapeutic Applications of Herbal Medicines for Cancer Patients

  2013cited by this paper
• Saikosaponin-d Enhances the Anticancer Potency of TNF-α via Overcoming Its Undesirable Response of Activating NF-Kappa B Signalling in Cancer Cells

  2013cited by this paper
• Sequential caspase-2 and caspase-8 activation is essential for saikosaponin a-induced apoptosis of human colon carcinoma cell lines

  2011cited by this paper
• Thermal Tumor Ablation in Clinical Use

  2011cited by this paper
• Protein folding and modification in the mammalian endoplasmic reticulum.

  2011cited by this paper
• Unfolded Proteins Are Ire1-Activating Ligands That Directly Induce the Unfolded Protein Response

  2011cited by this paper
• ROS-generating NADPH oxidase NOX4 is a critical mediator in oncogenic H-Ras-induced DNA damage and subsequent senescence

  2011cited by this paper
• Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells

  2010cited by this paper
• Cytotoxic activity and inhibitory effect on nitric oxide production of triterpene saponins from the roots of Physospermum verticillatum (Waldst & Kit) (Apiaceae).

  2009cited by this paper
• Endoplasmic reticulum stress and apoptosis

  2006cited by this paper
• Mediators of endoplasmic reticulum stress‐induced apoptosis

  2006cited by this paper
• The SERCA pump as a therapeutic target: Making a “smart bomb” for prostate cancer

  2005cited by this paper
• Coupling endoplasmic reticulum stress to the cell death program

  2004cited by this paper
• Roles of CHOP/GADD153 in endoplasmic reticulum stress

  2004cited by this paper
• The proliferative inhibition and apoptotic mechanism of Saikosaponin D in human non-small cell lung cancer A549 cells.

  2004cited by this paper
• Involvement of p53, nuclear factor kappaB and Fas/Fas ligand in induction of apoptosis and cell cycle arrest by saikosaponin d in human hepatoma cell lines.

  2004cited by this paper
• Saikosaponin-A induces apoptotic mechanism in human breast MDA-MB-231 and MCF-7 cancer cells.

  2003cited by this paper
• Endoplasmic reticulum dysfunction – a common denominator for cell injury in acute and degenerative diseases of the brain?

  2001cited by this paper
• Saikosaponins from roots of Bupleurum gibraltaricum and Bupleurum spinosum.

  2000cited by this paper
• Calcineurin functions in Ca(2+)-activated cell death in mammalian cells

  1995cited by this paper
• Calnexin: a membrane-bound chaperone of the endoplasmic reticulum.

  1994cited by this paper

• Emerging role of Saikosaponin A in tumor therapy and tumor microenvironment immunomodulation.

  2026cites this paper
• Research on the mechanisms of natural products in radiation protection

  2025cites this paper
• Exploring the Therapeutic Potential of Bupleurum in Medical Treatment: A Comprehensive Overview

  2025cites this paper
• Saikosaponin A Mediates the Anti-Acute Myeloid Leukemia Effect via the P-JNK Signaling Pathway Induced by Endoplasmic Reticulum Stress

  2025cites this paper
• Modulating Endoplasmic Reticulum Stress in Gastrointestinal Cancers: Insights from Traditional Chinese Medicine

  2024cites this paper
• Pharmacology, medical uses, and clinical translational challenges of Saikosaponin A: A review

  2024cites this paper
• The dual effect of endoplasmic reticulum stress in digestive system tumors and intervention of Chinese botanical drug extracts: a review

  2024cites this paper
• The circadian clock gene, BMAL1, promotes radiosensitization in nasopharyngeal carcinoma by inhibiting the epithelial-to-mesenchymal transition via the TGF-β1/Smads/Snail1 axis.

  2024cites this paper
• Exploring the Healing Powers of Saikosaponin A: A Review of Current Perspectives

  2024cites this paper
• Reactive oxygen species nanoamplifiers with multi-enzymatic activities for enhanced tumor therapy.

  2023cites this paper
• Paeoniflorin Induces ER Stress-Mediated Apoptotic Cell Death by Generating Nox4-Derived ROS under Radiation in Gastric Cancer

  2023cites this paper
• Efficacy and safety of the traditional herbal medication Chai-Ling-Tang (in China), Siryung-tang (in Republic of Korea) or Sairei-To (in Japan).

  2023cites this paper