ArticleMolecular medicine reports2021
Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer.
Article in Molecular medicine reports, 2021. 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, 39 citations in OpenAlex.
- Orchestrating glucose metabolism: PFKFB2 as a signal-integrating conductor in homeostasis and disease.The Journal of biological chemistry · 2026Review
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Recovering gene regulatory networks in single-cell multi-omics data with PRISM-GRN.Genome research · 2026Article
- Nanotechnology-based shikonin delivery strategies for modulating the tumor immune microenvironment efficacy.Drug delivery and translational research · 2026Review
- Constructing a sixteen lactate-related gene risk signature for LUAD to predict the prognosis and TME by machine learning.Scientific reports · 2025Article
- Shikonin as a Dietary Phytochemical with Multi-Target Anti-Cancer Activities: From Molecular Mechanisms to Translational Applications.Nutrients · 2025Review
- Spatial transcriptomic analysis across histological subtypes reveals molecular heterogeneity and prognostic markers in early-stage lung adenocarcinoma.Clinical and translational medicine · 2025Article
- Target identification of natural products in cancer with chemical proteomics and artificial intelligence approaches.Cancer biology & medicine · 2025Review
- Synergistic Effect of Ribitol and Shikonin Promotes Apoptosis in Breast Cancer Cells.International journal of molecular sciences · 2025Article
- A novel prognostic model for lung squamous cell carcinoma based on multi-omics analysis and machine learning.PloS one · 2025Article
- Shikonin induces the apoptosis and pyroptosis of EGFR-T790M-mutant drug-resistant non-small cell lung cancer cells via the degradation of cyclooxygenase-2.European journal of medical research · 2024Article
- Bioinformatics Analysis and Verification of Metabolic Abnormalities in Esophageal Squamous Carcinoma.Combinatorial chemistry & high throughput screening · 2024Article
- Hitting the Sweet Spot: How Glucose Metabolism Is Orchestrated in Space and Time by Phosphofructokinase-1.Cancers · 2023Review
- Phytochemicals Target Multiple Metabolic Pathways in Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- Comparative clinical significance and biological roles of PFKFB family members in oral squamous cell carcinoma.Cancer cell international · 2023Article
- Natural Plant-Derived Compounds in Food and Cosmetics: A Paradigm of Shikonin and Its Derivatives.Materials (Basel, Switzerland) · 2023Review
- Circular RNA Sec61 subunit alpha isoform 1 by competitive absorption of microRNA-513a-5p mediates peroxisomal biogenesis factor 5 expression and promotes the malignant phenotype of non-small cell lung cancer.The Kaohsiung journal of medical sciences · 2023Article
- Shikonin derivatives cause apoptosis and cell cycle arrest in human chondrosarcoma cells via death receptors and MAPK regulation.BMC cancer · 2022Article
- Role of Plant-Derived Active Constituents in Cancer Treatment and Their Mechanisms of Action.Cells · 2022Review
- Shikonin Derivatives Inhibit Inflammation Processes and Modulate MAPK Signaling in Human Healthy and Osteoarthritis Chondrocytes.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is one of the most lethal diseases and therefore poses a significant threat to human health. The Warburg effect, which is the observation that cancer cells predominately produce energy through glycolysis, even under aerobic conditions, is a hallmark of cancer. 6‑phosphofructo‑2‑kinase/fructose‑2,6‑biphosphatase 2 (PFKFB) is an important regulator of glycolysis. Shikonin is a Traditional Chinese herbal medicine, which has been reported to exert antitumor effects. The present study aimed to investigate the anticancer activity of shikonin in lung cancer. Cell Counting Kit‑8 (CCK‑8) and colony formation assays were used to analyze proliferation in A549 and H446 cells. Wound healing and Transwell assays were used to measure migration and invasion in A549 and H446 cells. Cell apoptosis was analyzed using flow cytometry. Lactate levels, glucose uptake and cellular ATP levels were measured using their corresponding commercial kits. Western blotting was performed to analyze the protein expression levels of key enzymes involved in aerobic glucose metabolism. Reverse transcription‑quantitative PCR was used to analyze the mRNA expression levels of PFKFB2. The results of the present study revealed that PFKFB2 expression levels were significantly upregulated in NSCLC tissues. Shikonin treatment decreased the proliferation, migration, invasion, glucose uptake, lactate levels, ATP levels and PFKFB2 expression levels and increased apoptosis in lung cancer cells in a dose‑dependent manner. The overexpression of PFKFB2 increased the proliferation, migration, glucose uptake, lactate levels and ATP levels in lung cancer cells, while the knockdown of PFKFB2 expression exerted the opposite effects. Moreover, there were no significant differences in lung cancer cell migration, apoptosis, glucose uptake, lactate levels and ATP levels between cells with knocked down PFKFB2 expression or treated with shikonin and the knockdown of PFKFB2 in cells treated with shikonin. In conclusion, the results of the present study revealed that shikonin inhibited the Warburg effect and exerted antitumor activity in lung cancer cells, which was associated with the downregulation of PFKFB2 expression.
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