ArticleThe Journal of biological chemistry2013
Effective killing of leukemia cells by the natural product OSW-1 through disruption of cellular calcium homeostasis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 63 citations in OpenAlex.
- Iron and Other Metal Ions in Human Health and Disease.MedComm · 2026Review
- Depletion of oxysterol-binding proteins by OSW-1 triggers RIP1/RIP3-independent necroptosis and sensitization to cancer immunotherapy.Cell death and differentiation · 2025Article
- OSW-1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma.Oncology letters · 2025Article
- Dysregulation of PI4P in the trans Golgi regions activates the mammalian Golgi stress response.The Journal of biological chemistry · 2025Article
- NCX1 disturbs calcium homeostasis and promotes RANKL-induced osteoclast differentiation by regulating JNK/c-Fos/NFATc1 signaling pathway in multiple myeloma.Clinical and experimental medicine · 2023Article
- Elucidation of OSW-1-Induced Stress Responses in Neuro2a Cells.International journal of molecular sciences · 2023Article
- OSW-1 induces apoptosis and cyto-protective autophagy, and synergizes with chemotherapy on triple negative breast cancer metastasis.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Article
- Small Molecule Targeting of Oxysterol-Binding Protein (OSBP)-Related Protein 4 and OSBP Inhibits Ovarian Cancer Cell Proliferation in Monolayer and Spheroid Cell Models.ACS pharmacology & translational science · 2021Article
- Anticancer Effects and Mechanisms of OSW-1 Isolated FromFrontiers in oncology · 2021Review
- Role of Sodium/Calcium Exchangers in Tumors.Biomolecules · 2020Review
- OSW-1 inhibits tumor growth and metastasis by NFATc2 on triple-negative breast cancer.Cancer medicine · 2020Article
- Inhibition of JNK-Mediated Autophagy Promotes Proscillaridin A- Induced ApoptosisFrontiers in pharmacology · 2020Article
- Progress in understanding mitochondrial calcium uniporter complex-mediated calcium signalling: A potential target for cancer treatment.British journal of pharmacology · 2019Review
- Transient Compound Treatment Induces a Multigenerational Reduction of Oxysterol-Binding Protein (OSBP) Levels and Prophylactic Antiviral Activity.ACS chemical biology · 2019Article
- Lipid Transfer Proteins and Membrane Contact Sites in Human Cancer.Frontiers in cell and developmental biology · 2019Review
- Cholestane glycosides from Ornithogalum saundersiae bulbs and the induction of apoptosis in HL-60 cells by OSW-1 through a mitochondrial-independent signaling pathway.Journal of natural medicines · 2019Article
- Cinnamaldehyde, a Promising Natural Preservative AgainstFrontiers in microbiology · 2019Article
- Targeting calcium signaling in cancer therapy.Acta pharmaceutica Sinica. B · 2017Review
- NFκB activation demarcates a subset of hepatocellular carcinoma patients for targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2016Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
3β,16β,17α-Trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-β-D-xylopyranosyl)-(1→3)-2-O-acetyl-α-L-arabinopyranoside (OSW-1) is a natural product with potent antitumor activity against various types of cancer cells, but the exact mechanisms of action remain to be defined. In this study, we showed that OSW-1 effectively killed leukemia cells at subnanomolar concentrations through a unique mechanism by causing a time-dependent elevation of cytosolic Ca(2+) prior to induction of apoptosis. A mechanistic study revealed that this compound inhibited the sodium-calcium exchanger 1 on the plasma membrane, leading to an increase in cytosolic Ca(2+) and a decrease in cytosolic Na(+). The elevated cytosolic Ca(2+) caused mitochondrial calcium overload and resulted in a loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3. Furthermore, OSW-1 also caused a Ca(2+)-dependent cleavage of the survival factor GRP78. Inhibition of Ca(2+) entry into the mitochondria by the uniporter inhibitor RU360 or by cyclosporin A significantly prevented the OSW-1-induced cell death, indicating the important role of mitochondria in mediating the cytotoxic activity. The extremely potent activity of OSW-1 against leukemia cells and its unique mechanism of action suggest that this compound may be potentially useful in the treatment of leukemia.
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