ArticleMolecular carcinogenesis2014
PKM2 inhibitor shikonin suppresses TPA-induced mitochondrial malfunction and proliferation of skin epidermal JB6 cells.
Article in Molecular carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
- Review
- Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Translocalization of enhanced PKM2 protein into the nucleus induced by cancer upregulated gene 2 confers cancer stem cell-like phenotypes.BMB reports · 2022Article
- Natural products targeting glycolytic signaling pathways-an updated review on anti-cancer therapy.Frontiers in pharmacology · 2022Review
- TEM1-targeting PEGylated PLGA shikonin nanoformulation for immunomodulation and eradication of ovarian cancer.BioImpacts : BI · 2022Article
- Shikonin regulates autophagy via the AMPK/mTOR pathway and reduces apoptosis of human umbilical cord mesenchymal stem cells to improve survival in tissues surrounding brain contusion.Experimental and therapeutic medicine · 2021Article
- Current Development and Application of Anaerobic Glycolytic Enzymes in Urothelial Cancer.International journal of molecular sciences · 2021Review
- The role and mechanism of PKM2 in the development of LPS-induced acute kidney injury.Histology and histopathology · 2021Article
- Article
- Competitive glucose metabolism as a target to boost bladder cancer immunotherapy.Nature reviews. Urology · 2020Review
- Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia.Mediators of inflammation · 2020Article
- Deoxyshikonin Inhibits Viability and Glycolysis by Suppressing the Akt/mTOR Pathway in Acute Myeloid Leukemia Cells.Frontiers in oncology · 2020Article
- The role of pyruvate kinase M2 in anticancer therapeutic treatments.Oncology letters · 2019Review
- A critical review of the role of MBiochimica et biophysica acta. Reviews on cancer · 2019Review
- Drugging cancer metabolism: Expectations vs. reality.International review of cell and molecular biology · 2019Review
- Synthesis and antitumor activity of novel 2, 3-didithiocarbamate substituted naphthoquinones as inhibitors of pyruvate kinase M2 isoform.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Down-regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer.Journal of cellular and molecular medicine · 2018Article
- Shikonin causes apoptosis by disrupting intracellular calcium homeostasis and mitochondrial function in human hepatoma cells.Experimental and therapeutic medicine · 2018Article
- Tyrosine Kinase Signaling in Cancer Metabolism: PKM2 Paradox in the Warburg Effect.Frontiers in cell and developmental biology · 2018Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Chemoprevention has been a pivotal and effective strategy during the skin cancer treatment. Using human skin normal and tumor samples, we demonstrated that both the expression and activity levels of pyruvate kinase M2 (PKM2) were higher in skin tumor tissues than normal tissues, suggesting that PKM2, one of important metabolic enzyme, might serve as a target for skin cancer prevention and/or therapy. Shikonin, a small-molecule active chemical, has been studied as an anti-cancer drug candidate in human cancer models. However, the mechanism of action and the chemopreventive potential of shikonin are unclear. Herein, we used the skin epidermal JB6 P+ cells and demonstrated that shikonin suppressed the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) induced neoplastic cell transformation and PKM2 activation in the early stage of carcinogenesis. Mitochondrial functions were inhibited by TPA treatment, as indicated by reduced mitochondrial membrane potential and mitochondrial respiration, which were restored by shikonin. We also examined the levels of lactate as a glycolysis marker, and shikonin suppressed its increase caused by tumor promoter treatment. Modulation of cell metabolism by shikonin was associated with G2-M phase accumulation, and Fra-1 (a major subunit of activator protein 1 in skin tumorigenesis) downregulation. In addition, we demonstrated that AMP-activated protein kinase (AMPK), an energy sensor, which is inactivated by TPA, shikonin could reverse AMPK activity. These results suggest that shikonin bears chemopreventive potential for human skin cancers in which PKM2 is upregulated, which might be mediated by inhibiting oncogenic activation, PKM2 activation, and mitochondrial dysfunction.
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