ArticleCell death & disease2019
β-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38/ERK MAPK signaling in human hepatocellular carcinoma.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 146 citations in OpenAlex.
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- Long Noncoding RNA NONHSAT233728.1 Promotes ROS Accumulation and Granulosa Cell Apoptosis by Regulating the MAPK/ERK1/2 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.Cellular & molecular biology letters · 2025Review
- Erk1/2 Orchestrates SSPH I-Induced Oxidative Stress, Mitochondrial Dysfunction and Ferroptosis in Hepatocellular Carcinoma.Journal of cellular and molecular medicine · 2025Article
- The Mechanism of a Novel Mitochondrial-Targeted Icaritin Derivative in Regulating Apoptosis of BEL-7402 Cells Based on the SIRT3 and CypD-Mediated ROS/p38 MAPK Signaling Pathway.Molecules (Basel, Switzerland) · 2025Article
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- Lactoferrin targeting INTL1 receptor inhibits hepatocellular carcinoma progression via apoptosis and cell cycle signaling pathways.Scientific reports · 2024Article
- Anti-cancer activity and cellular uptake of 7,3',4'- and 7,8,4'-trihydroxyisoflavone in HepG2 cells under hypoxic conditions.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Podocyte Death in Diabetic Kidney Disease: Potential Molecular Mechanisms and Therapeutic Targets.International journal of molecular sciences · 2024Review
- Intracellular magnetic hyperthermia reverses sorafenib resistance in hepatocellular carcinoma through its action on signaling pathways.iScience · 2024Article
- Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway.International journal of molecular sciences · 2024Article
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- Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC), a common liver malignancy worldwide, has high morbidity and mortality. β-Thujaplicin, a tropolone derivative, has been used in some health-care products and clinical adjuvant drugs, but its use for HCC is unknown. In this study, we found that β-Thujaplicin inhibits the growth of HCC cells, but not normal liver cells, with nanomolar potency. Mechanistically, we found that β-Thujaplicin could induce autophagy, as judged by western blot, confocal microscopy, and transmission electron microscopy. Further using β-Thujaplicin combined with an autophagy blocker or agonist treatment HepG2 cells, we found that β-Thujaplicin induced autophagic cell death (ACD) mediated by ROS caused inhibition of the Akt-mTOR signaling pathway. Moreover, β-Thujaplicin triggered HepG2 apoptosis and increased cleaved PARP1, cleaved caspase-3, and Bax/Bcl-2 ratio, which indicated that β-Thujaplicin induced apoptosis mediated by the mitochondrial-dependent pathway. We also found that increased expression of p21 and decreased expression of CDK7, Cyclin D1, and Cyclin A2 participating in β-Thujaplicin caused the S-phase arrest. It seems that β-Thujaplicin exerts these functions by ROS-mediated p38/ERK MAPK but not by JNK signaling pathway activation. Consistent with in vitro findings, our in vivo study verified that β-Thujaplicin treatment significantly reduced HepG2 tumor xenograft growth. Taken together these findings suggest that β-Thujaplicin have an ability of anti-HCC cells and may conducively promote the development of novel anti-cancer agents.
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