ArticleAmerican journal of cancer research2021
Inhibition of BAG3 enhances the anticancer effect of shikonin in hepatocellular carcinoma.
Article in American journal of cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Knockdown of CREB3L4 Inhibits Autophagy and Reduces Cisplatin Resistance in Gastric Cancer Cells by Downregulating BAG3.The Kaohsiung journal of medical sciences · 2026Article
- Shikonin in Hepatocellular Carcinoma: Bridging Metabolic Disruption and Immunomodulation.Journal of hepatocellular carcinoma · 2026Review
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- SQSTM1/p62 Mediates the Effects of CPNE3 on the Epithelialmesenchymal Transition and Migration Inhibition of Lung Adenocarcinoma Cells.Current medicinal chemistry · 2025Article
- Targeting PKM2 in cancer therapeutics: mechanistic advances and translational opportunities.Frontiers in immunology · 2025Review
- HSPB1 silencing enhances ferroptosis in glioma cells by suppressing BAG3 expression.American journal of translational research · 2025Article
- Shikonin Induces Autophagy and Apoptosis in Esophageal Cancer EC9706 Cells by Regulating the AMPK/mTOR/ULK Axis.Analytical cellular pathology (Amsterdam) · 2024Article
- Glycolysis in Chronic Liver Diseases: Mechanistic Insights and Therapeutic Opportunities.Cells · 2023Review
- PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats.Journal of pharmaceutical analysis · 2023Article
- Metabolic rearrangements and intratumoral heterogeneity for immune response in hepatocellular carcinoma.Frontiers in immunology · 2023Review
- Shikonin induces apoptosis and autophagy via downregulation of pyrroline-5-carboxylate reductase1 in hepatocellular carcinoma cells.Bioengineered · 2022Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human hepatocellular carcinoma (HCC) is the most frequent cancer worldwide with a poor prognosis. Tumor-specific pyruvate kinase M2 (PKM2) is essential for cancer metabolism and tumorigenesis. Shikonin, a specific inhibitor of PKM2, but not PKM1, exhibits significant anticancer effect in HCC, and was deemed as a promising drug for cancer therapy. However, shikonin-mediated bypass signaling in HCC remained unclear. Here, we performed forward/reverse stable isotope labeling with amino acids in cell culture (SILAC)-based proteomics to identify the early molecular events controlled by shikonin. We demonstrated for the first time that shikonin could induce the nuclear translocation of PKM2 for recruiting Nrf2, and transcriptionally activated Nrf2 downstream target gene BAG3, therefore increasing protective effect to sustain cell survival. Knockdown of BAG3 by si-RNA significantly potentiated the anticancer effect of shikonin. These findings provided the first evidence of a new noncanonical function of inhibited PKM2 could act as a transcriptional coactivator of Nrf2 in cancer survival, highlight that shikonin in combined with BAG3 inhibitor could be a promising therapeutic strategy for HCC therapy.
Indexed as
Identifiers
34354861PMC8332868W3192584965What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.