ArticleBMC cancer2013
The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosis.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.
- Chinese Herbal Medicine for Osteosarcoma in the Mouse: A Systematic Review and Meta-Analysis.Chinese journal of integrative medicine · 2019Pooled it
- Natural products reshape osteosarcoma cell fate: promoting cell death.Frontiers in pharmacology · 2026Review
- The Multitalented Marvels: Exploring the Versatile Potential of Natural Products in Osteosarcoma Treatment.Cancer informatics · 2026Review
- Bypassing the guardian: regulated cell death pathways in p53-mutant cancers.Cellular & molecular biology letters · 2025Review
- XMU-MP-1, Inhibitor of STE20-like MST1/2 Kinases of the Hippo Signaling Pathway, Suppresses the Cell Cycle, Activates Apoptosis and Autophagy, and Induces Death of Hematopoietic Tumor Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Specific signaling pathways mediated programmed cell death in tumor microenvironment and target therapies.Discover oncology · 2025Review
- Identification of necroptosis & mitophagy-related key genes and their prognostic value in colorectal cancer.Discover oncology · 2025Article
- Interfering with UBE2L3 expression targets regulation of MLKL to promote necroptosis inhibition of growth in osteosarcoma.World journal of surgical oncology · 2025Article
- Apoptotic signaling pathways in bone metastatic lung cancer: a comprehensive analysis.Discover oncology · 2024Review
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Pharmacological Significance ofFoods (Basel, Switzerland) · 2024Review
- Transcriptome and single-cell analysis reveal disulfidptosis-related modification patterns of tumor microenvironment and prognosis in osteosarcoma.Scientific reports · 2024Article
- Differential antiangiogenic and anticancer activities of the active metabolites of ginsenoside Rg3.Journal of ginseng research · 2024Article
- Identification and Validation of a Necroptosis-Related Prognostic Model in Tumor Recurrence and Tumor Immune Microenvironment in Breast Cancer Management.Journal of inflammation research · 2024Article
- Development of a novel vasculogenic mimicry-associated gene signature for the prognostic assessment of osteosarcoma patients.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Shikonin Causes an Apoptotic Effect on Human Kidney Cancer Cells through Ras/MAPK and PI3K/AKT Pathways.Molecules (Basel, Switzerland) · 2023Article
- Apoptotic effect and cell arrest of deoxyshikonin in human osteosarcoma cells through the p38 pathway.Journal of cellular and molecular medicine · 2023Article
- A bibliometric analysis of ferroptosis, necroptosis, pyroptosis, and cuproptosis in cancer from 2012 to 2022.Cell death discovery · 2023Article
- Necroptosis Induced by Delta-Tocotrienol Overcomes Docetaxel Chemoresistance in Prostate Cancer Cells.International journal of molecular sciences · 2023Article
- Bacterial responses to plant antimicrobials: the case of alkannin and shikonin derivatives.Frontiers in pharmacology · 2023Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsteosarcoma is the most frequent primary malignant bone tumor, notorious for its lung metastasis. Shikonin, an effective constituent extracted from Chinese medicinal herb, was demonstrated to induce necroptosis in some cancers.
methodsMTT assay was performed to detect cell survival rate in vitro. Flow cytometry was used to analyze cell cycle and cell death. Western blot was performed to determine the expression levels of RIP1, RIP3, caspase-3, caspase-6 and PARP. The tibial primary and lung metastatic osteosarcoma models were used to evaluate the anti-tumor effect of shikonin in vivo.
resultsThe cell survival rate was decreased in a dose and time dependent manner when treated with shikonin. No major change in cell cycle was observed after shikonin treatment. The cell death induced by shikonin could be mostly rescued by specific necroptosis inhibitor necrostatin-1, but not by general caspase inhibitor Z-VAD-FMK. The number of necrotic cells caused by shikonin was decreased after being pretreated with Nec-1 detected by flow cytometry in K7 cells. After 8-hour treatment of shikonin, the expression levels of RIP1 and RIP3 were increased while caspase-3, caspase-6 and PARP were not activated in K7 and U2OS cells determined by Western blot. Size of primary tumor and lung metastasis in shikonin treated group were significantly reduced. The protein levels of RIP1 and RIP3 in primary tumor tissues were increased by shikonin. The overall survival of lung metastatic models was longer compared with control group (p < 0.001).
conclusionsShikonin had prompt but profound anti-tumor effect on both primary and metastatic osteosarcoma, probably by inducing RIP1 and RIP3 dependent necroptosis. Shikonin would be a potential anti-tumor agent on the treatment of primary and metastatic osteosarcoma.
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