ArticleAmerican journal of cancer research2016
P53 is required for Doxorubicin-induced apoptosis via the TGF-beta signaling pathway in osteosarcoma-derived cells.
Article in American journal of cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- Epinecidin-1 Induces Distinct Oncosis and Pyroptosis Responses in Osteosarcoma Cells and Enhances Methotrexate-associated Cytotoxicity.Probiotics and antimicrobial proteins · 2026Article
- The miR-16-1-3p suppresses proliferation and invasiveness via the MDM2-p53 axis in TGF-β1 signaling in osteosarcoma.Molecular therapy. Oncology · 2026Article
- Article
- Pathways of Resistance: Modern Multiple Myeloma Therapies and Overcoming Reliance on Genomic Integrity.International journal of molecular sciences · 2026Review
- A design-of-experiments strategy for engineering 3D topographical features in osteosarcoma modelling.Materials today. Bio · 2025Article
- Anti-leukemia activity of the ethyl acetate extract from Gynostemma pentaphyllum (Thunb.) leaf against FLT3-overexpressing AML cells and its phytochemical characterization.BMC complementary medicine and therapies · 2025Article
- The Role of Epithelial-Mesenchymal Transition in Osteosarcoma Progression: From Biology to Therapy.Diagnostics (Basel, Switzerland) · 2025Review
- Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53.Frontiers in pharmacology · 2025Review
- TRIM-endous functional network of tripartite motif 29 (TRIM29) in cancer progression and beyond.Cancer metastasis reviews · 2024Review
- Osteosarcoma-Associated Immune Genes as Potential Immunotherapy and Prognosis Biomarkers.Biochemical genetics · 2024Article
- Transgenic construction and functional miRNA analysis identify the role of miR-7 in prostate cancer suppression.Oncogene · 2022Article
- CD44 Contributes to the Regulation of MDR1 Protein and Doxorubicin Chemoresistance in Osteosarcoma.International journal of molecular sciences · 2022Article
- Advanced Strategies for Therapeutic Targeting of Wild-Type and Mutant p53 in Cancer.Biomolecules · 2022Review
- TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway.International journal of oncology · 2021Article
- Pharmacologic inhibition of Akt in combination with chemotherapeutic agents effectively induces apoptosis in ovarian and endometrial cancer cell lines.Molecular oncology · 2021Article
- miR‑29b suppresses proliferation and induces apoptosis of hepatocellular carcinoma ascites H22 cells via regulating TGF‑β1 and p53 signaling pathway.International journal of molecular medicine · 2021Article
- Germacranolides fromMolecules (Basel, Switzerland) · 2021Article
- The role of P53 up-regulated modulator of apoptosis (PUMA) in ovarian development, cardiovascular and neurodegenerative diseases.Apoptosis : an international journal on programmed cell death · 2021Review
- Identification of Gene as Predictive Biomarkers for the Occurrence and Recurrence of Osteosarcoma.International journal of general medicine · 2021Article
- Synthesis of new thienylpicolinamidine derivatives and possible mechanisms of antiproliferative activity.RSC advances · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma is the most common type of aggressive bone cancer. Current treatment strategies include surgical resection, radiation, and chemotherapy. Doxorubicin has been widely used as a chemotherapeutic drug to treat osteosarcoma. However, drug resistance has become a challenge to its use. In this study, p53-wild type U2OS and p53-null MG-63 osteosarcoma-derived cells were used to investigate the mechanism of doxorubicin-induced cytotoxicity. In cell viability assays, doxorubicin effectively induced apoptosis in U2OS cells via the p53 signaling pathway, evidenced by elevated PUMA and p21 protein levels and activated caspase 3 cleavage. In contrast, p53-null MG-63 cells were resistant to doxorubicin-induced apoptosis, while exogenous expression of p53 increased drug sensitivity in those cells. The role of TGF-β/Smad3 signaling was investigated by using TGF-β reporter luciferase assays. Doxorubicin was able to induce TGF-β signal transduction without increasing TGF-β production in the presence of p53. Knockdown of Smad3 expression by small hairpin RNA (shRNA) showed that Smad3 was required for p53-mediated TGF-β signaling in response to doxorubicin treatment in U2OS and MG-63 cells. Taken together, these data demonstrate that p53 and TGF-β/Smad3 signaling pathways are both essential for doxorubicin-induced cytotoxicity in osteosarcoma cells.
Indexed as
Identifiers
27073729PMC4759403W2338394708What 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.