ArticleMolecules (Basel, Switzerland)2013
Sinulariolide induced hepatocellular carcinoma apoptosis through activation of mitochondrial-related apoptotic and PERK/eIF2α/ATF4/CHOP pathway.
Article in Molecules (Basel, Switzerland), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- Pinpointing an innovative autophagic signature as a prognostic and diagnostic biomarkers in colorectal carcinoma.Future science OA · 2025Article
- Analysis of Cembrane-Type Diterpenoids from Cultured Soft CoralInternational journal of molecular sciences · 2025Article
- Prenatal Exposure to Dibutyl Phthalate and Its Negative Health Effects on Offspring: In Vivo and Epidemiological Studies.Journal of xenobiotics · 2024Review
- Marine-Derived Anticancer Agents Targeting Apoptotic Pathways: Exploring the Depths for Novel Cancer Therapies.Marine drugs · 2024Review
- Article
- Sinulariolide Suppresses Inflammation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis and Mitigates Collagen-Induced Arthritis Symptoms in Mice.Journal of inflammation research · 2024Article
- Review
- Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38-NF-kB Pathway in Carcinoma Cells.International journal of molecular sciences · 2023Article
- Crosstalk between endoplasmic reticulum stress and multidrug-resistant cancers: hope or frustration.Frontiers in pharmacology · 2023Review
- Exploring the Role of Endoplasmic Reticulum Stress in Hepatocellular Carcinoma through mining of the Human Protein Atlas.Biology · 2021Article
- Naringin Combined with NF-κB Inhibition and Endoplasmic Reticulum Stress Induces Apoptotic Cell Death via Oxidative Stress and the PERK/eIF2α/ATF4/CHOP Axis in HT29 Colon Cancer Cells.Biochemical genetics · 2021Article
- Review
- VDMolecular biology reports · 2020Article
- A New Method for Collecting Large Amounts of Symbiotic Gastrodermal Cells from Octocorals.International journal of molecular sciences · 2020Article
- Isoferulic acid inhibits human leukemia cell growth through induction of G2/M‑phase arrest and inhibition of Akt/mTOR signaling.Molecular medicine reports · 2020Article
- Article
- Proteomic analysis of retinal pigment epithelium cells after exposure to UVA radiation.BMC ophthalmology · 2019Article
- Marine Natural Products from Indonesian Waters.Marine drugs · 2019Review
- Role of PERK-eIF2α signaling pathway in fetal male rats with hypospadias induced by di-n-butyl phthalate.The Kaohsiung journal of medical sciences · 2018Article
- Z-FL-COCHO, a cathepsin S inhibitor, enhances oxaliplatin-mediated apoptosis through the induction of endoplasmic reticulum stress.Experimental & molecular medicine · 2018Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sinulariolide, an active compound isolated from the cultured soft coral Sinularia flexibilis, has potent anti-microbial and anti-tumorigenesis effects towards melanoma and bladder cancer cells. In this study, we investigated the effects of sinulariolide on hepatocellular carcinoma (HCC) cell growth and protein expression. Sinulariolide suppressed the proliferation and colony formation of HCC HA22T cells in a dose-dependent manner and induced both early and late apoptosis according to flow cytometry, Annexin V/PI stain and TUNEL/DAPI stain analyses. A mechanistic analysis demonstrated that sinulariolide-induced apoptosis was activated through a mitochondria-related pathway, showing up-regulation of Bax, Bad and AIF, and down- regulation of Bcl-2, Bcl-xL, MCl-1 and p-Bad. Sinulariolide treatment led to loss of the mitochondrial membrane potential, release of mitochondrial cytochrome c to the cytosol, and activation of both caspase-9 and caspase-3. Sinulariolide-induced apoptosis was significantly blocked by the caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK. The increased expression of cleaved PARP also suggested that caspase-independent apoptotic pathway was involved. In the western blotting; the elevation of ER chaperones GRP78; GRP94; and CALR; as well as up-regulations of PERK/eIF2α/ATF4/CHOP; and diminished cell death with pre-treatment of eIF2α phosphatase inhibitor; salubrinal; implicated the involvement of ER stress-mediated PERK/eIF2α/ATF4/CHOP apoptotic pathway following sinulariolide treatment in hepatoma cells. The current study suggested sinulariolide-induced hepatoma cell cytotoxicity involved multiple apoptotic signal pathways. This may implicate that sinulariolide is a potential compound for the treatment of hepatocellular carcinoma.
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Registered trials
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