ArticleCancer science2014
Gambogic acid suppresses hypoxia-induced hypoxia-inducible factor-1α/vascular endothelial growth factor expression via inhibiting phosphatidylinositol 3-kinase/Akt/mammalian target protein of rapamycin pathway in multiple myeloma cells.
Article in Cancer science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Mechanistic and translational insights into plant-derived natural products in preclinical multiple myeloma research: Current evidence.Translational oncology · 2026Review
- Antitumor effects and mechanisms of traditional Chinese medicine gamboge: A review.Frontiers in pharmacology · 2025Review
- Synergistic Mechanisms of Traditional Chinese Medicine and Proteasome Inhibitors in Multiple Myeloma Therapy: A Comprehensive Review.Drug design, development and therapy · 2025Review
- Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.Acta pharmaceutica Sinica. B · 2024Article
- Bioactive Phytoconstituents and Their Therapeutic Potentials in the Treatment of Haematological Cancers: A Review.Life (Basel, Switzerland) · 2023Review
- Phytochemicals as Regulators of Tumor Glycolysis and Hypoxia Signaling Pathways: Evidence from In Vitro Studies.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology.Frontiers in pharmacology · 2022Review
- Active Components of Traditional Chinese Medicinal Material for Multiple Myeloma: Current Evidence and Future Directions.Frontiers in pharmacology · 2022Review
- Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha.International journal of molecular sciences · 2021Review
- Review
- Targeting the Endothelin-1 Receptors Curtails Tumor Growth and Angiogenesis in Multiple Myeloma.Frontiers in oncology · 2020Article
- The Role of mTOR Inhibitors in Hematologic Disease: From Bench to Bedside.Frontiers in oncology · 2020Review
- Gambogic Acid as a Candidate for Cancer Therapy: A Review.International journal of nanomedicine · 2020Review
- Tanshinone IIA inhibits glucose metabolism leading to apoptosis in cervical cancer.Oncology reports · 2019Article
- Gambogic acid increases the sensitivity to paclitaxel in drug‑resistant triple‑negative breast cancer via the SHH signaling pathway.Molecular medicine reports · 2019Article
- A Recombinant Affinity Reagent Specific for a Phosphoepitope of Akt1.International journal of molecular sciences · 2018Article
- Combining the mammalian target of rapamycin inhibitor, rapamycin, with resveratrol has a synergistic effect in multiple myeloma.Oncology letters · 2018Article
- TRIM56 Suppresses Multiple Myeloma Progression by Activating TLR3/TRIF Signaling.Yonsei medical journal · 2018Article
- RNAi-mediated knockdown of MCM7 gene on CML cells and its therapeutic potential for leukemia.Medical oncology (Northwood, London, England) · 2017Article
- Gambogenic Acid Exerts Antitumor Activity in Hypoxic Multiple Myeloma Cells by Regulation of miR-21.Journal of Cancer · 2017Article
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10 authors.
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Abstract
In multiple myeloma (MM), the hypoxic environment is an important factor causing tumor angiogenesis, which is strongly correlated to disease progression and unfavorable outcome by activating the key transcription factor, hypoxia-inducible factor-1α (HIF-1α). Gambogic acid (GA) is the major active ingredient of gamboge, which has been shown to possess antitumor effect by in vitro and in vivo study. However, the underlying molecular mechanism of whether GA inhibits tumor angiogenesis remains poorly understood. In this study, we investigated the effects of GA on expression of HIF-1α, and its downstream target gene vascular endothelial growth factor (VEGF) in human MM U266 cells. We found that hypoxia induced increase in the level of HIF-1α subunit protein and activated the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target protein of rapamycin (mTOR) pathway. Moreover, the treatment with GA markedly decreased HIF-1α and VEGF expression under hypoxic conditions. Mechanistic studies exhibited that GA inhibited the production of HIF-1α by reducing phosphorylation of Akt and mTOR in U266 cells. Furthermore, in vivo study revealed that intravenous injection of GA once every other day for 2 weeks could suppress tumor volumes by antiangiogenesis activity. Taken together, our results identify that GA suppresses hypoxia-activated pathways that are linked to MM progression, at least partly, by the inhibition of the PI3K/Akt/mTOR signaling pathway. Therefore, GA may be a new potent therapeutic agent against human MM cells.
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