ArticleInternational journal of cancer2009
Shikonin exerts antitumor activity via proteasome inhibition and cell death induction in vitro and in vivo.
Article in International journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 156 citations in OpenAlex.
- Clinical implications of lactylation modification in digestive system tumors (Review).Oncology letters · 2026Review
- The ginger-derived nanovesicles-coated albumin nanoparticles induce cell death and epigenetic regulation to treat colorectal cancer.Discover nano · 2026Article
- Empowering of novel anti-tumor formulations with quinone-based active natural products.Biomaterials translational · 2026Review
- Targeting the proteasome in cancer therapy: development and future opportunities in natural products.Frontiers in pharmacology · 2026Review
- Synergistic Effect of Ribitol and Shikonin Promotes Apoptosis in Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Harnessing the role of aberrant cell signaling pathways in glioblastoma multiforme: a prospect towards the targeted therapy.Molecular biology reports · 2024Review
- Shikonin reduces M2 macrophage population in ovarian cancer by repressing exosome production and the exosomal galectin 3-mediated β-catenin activation.Journal of ovarian research · 2024Article
- Evolution of Natural Product Scaffolds as Potential Proteasome Inhibitors in Developing Cancer Therapeutics.Metabolites · 2023Review
- Bacterial responses to plant antimicrobials: the case of alkannin and shikonin derivatives.Frontiers in pharmacology · 2023Article
- The anti-leukemia activity and mechanisms of shikonin: a mini review.Frontiers in pharmacology · 2023Review
- Cosmeceutical Therapy: Engaging the Repercussions of UVR Photoaging on the Skin's Circadian Rhythm.International journal of molecular sciences · 2022Review
- Shikonin Mediates Apoptosis through G Protein-Coupled Estrogen Receptor of Ovarian Cancer Cells.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs.International journal of molecular sciences · 2021Review
- Targeting Cancer Metabolism and Current Anti-Cancer Drugs.Advances in experimental medicine and biology · 2021Review
- Natural product scaffolds as inspiration for the design and synthesis of 20S human proteasome inhibitors.RSC chemical biology · 2020Article
- Shikonin potentiates paclitaxel antitumor efficacy in esophageal cancer cells via the apoptotic pathway.Oncology letters · 2019Article
- Analysis of the Mechanisms of Action of Naphthoquinone-Based Anti-Acute Myeloid Leukemia Chemotherapeutics.Molecules (Basel, Switzerland) · 2019Review
- Combination of shikonin with paclitaxel overcomes multidrug resistance in human ovarian carcinoma cells in a P-gp-independent manner through enhanced ROS generation.Chinese medicine · 2019Article
- The diverse mechanisms and anticancer potential of naphthoquinones.Cancer cell international · 2019Review
- Regulatory elements in vectors containing the ctEF-1α first intron and double enhancers for an efficient recombinant protein expression system.Scientific reports · 2018Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Dysregulation of the ubiquitin-proteasome pathway plays an essential role in tumor growth and development. Shikonin, a natural naphthoquinone isolated from the traditional Chinese medicine Zi Cao (gromwell), has been reported to possess tumor cell-killing activity, and results from a clinical study using a shikonin-containing mixture demonstrated its safety and efficacy for the treatment of late-stage lung cancer. In this study, we reported that shikonin is an inhibitor of tumor proteasome activity in vitro and in vivo. Our computational modeling predicts that the carbonyl carbons C(1) and C(4) of shikonin potentially interact with the catalytic site of beta 5 chymotryptic subunit of the proteasome. Indeed, shikonin potently inhibits the chymotrypsin-like activity of purified 20S proteasome (IC(50) 12.5 micromol/L) and tumor cellular 26S proteasome (IC(50) between 2-16 micromol/L). Inhibition of the proteasome by shikonin in murine hepatoma H22, leukemia P388 and human prostate cancer PC-3 cultures resulted in accumulation of ubiquitinated proteins and several proteasome target proapoptotic proteins (I kappaB-alpha, Bax and p27), followed by induction of cell death. Shikonin treatment resulted in tumor growth inhibition in both H22 allografts and PC-3 xenografts, associated with suppression of the proteasomal activity and induction of cell death in vivo. Finally, shikonin treatment significantly prolonged the survival period of mice bearing P388 leukemia. Our results indicate that the tumor proteasome is one of the cellular targets of shikonin and inhibition of the proteasome activity by shikonin contributes to its antitumor property.
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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.