ArticleCell death & disease2017
MK2206 enhances the cytocidal effects of bufalin in multiple myeloma by inhibiting the AKT/mTOR pathway.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
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- Targeting the HuR/E2F7 axis synergizes with bortezomib against multiple myeloma.Acta pharmacologica Sinica · 2025Article
- Peimine induces apoptosis of glioblastoma cells through regulation of the PI3K/AKT signaling pathway.Experimental and therapeutic medicine · 2024Article
- The Role of Cytokines in Activation of Tumour-promoting Pathways and Emergence of Cancer Drug Resistance.Current topics in medicinal chemistry · 2024Review
- The role of Aha1 in cancer and neurodegeneration.Frontiers in molecular neuroscience · 2024Review
- Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.Drug design, development and therapy · 2024Review
- New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.Acta pharmaceutica Sinica. B · 2022Review
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- New AKT-dependent mechanisms of anti-COVID-19 action of high-CBD Cannabis sativa extracts.Cell death discovery · 2022Article
- Activating BK channels ameliorates vascular smooth muscle calcification through Akt signaling.Acta pharmacologica Sinica · 2022Article
- The identities of insulin signaling pathway are affected by overexpression of Tau and its phosphorylation form.Frontiers in aging neuroscience · 2022Article
- Active Components of Traditional Chinese Medicinal Material for Multiple Myeloma: Current Evidence and Future Directions.Frontiers in pharmacology · 2022Review
- PI3K/AKT/mTOR signalling pathway involvement in renal cell carcinoma pathogenesis (Review).Experimental and therapeutic medicine · 2021Review
- Review
- Huanglian Jiedu Decoction for treatment of multiple myeloma: A protocol for a systematic review and meta-analysis.Medicine · 2020Article
- Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain.International journal of molecular medicine · 2020Article
- Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-β1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro.BMC complementary medicine and therapies · 2020Article
- PHLPP Sensitizes Multiple Myeloma Cells to Bortezomib Through Regulating LAMP2.OncoTargets and therapy · 2020Article
- Article
- mTOR inhibitor Everolimus-induced apoptosis in melanoma cells.Journal of cell communication and signaling · 2019Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the development of promising cancer therapeutic drugs, multiple myeloma (MM) remains an incurable disease. Bufalin is a bufanolide steroid compound of the traditional Chinese medicine Chan Su that was previously shown to exert growth suppression effects on myeloma cell lines. Previous studies conducted by our group demonstrated that bufalin activated the AKT/mTOR pathway in myeloma cells, which is considered an essential pathway to disease progression and is related to drug resistance in MM. In view of the significant role of AKT in MM, the allosteric AKT inhibitor MK2206 was selected in order to enhance the antitumor effects of bufalin in different MM cell lines (NCI-H929, U266, LP-1 and RPMI8226). The data indicated that MK2206 enhanced the cytotoxicity of bufalin in MM cells, via the suppression of cellular proliferation and the induction of apoptosis, as demonstrated by cleavage of apoptosis-related proteins. This effect was further noted in the presence of exogenous interleukin-6 and/or following the co-culture of MM cells with bone marrow stromal cells (BMSC). This process was associated with the inhibition of the AKT/mTOR pathway. The combination of bufalin with MK2206 reduced the secretion of IL-6 in U266 cells. The combined treatment exhibited similar anti-MM effects in bortezomib-resistant cell lines (NCI-H929R, U266R). In addition to the in vitro cell line models, the synergistic effect was noted in primary MM cells and in MM xenografts of BALB-c and NOD-SCID mice. In conclusion, the data suggested that MK2206 significantly enhanced the cytocidal effects of bufalin in MM cells, regardless of the sensitivity to bortezomib, via the inhibition of the AKT/mTOR pathway. The study provided the basis of a promising treatment approach for MM.
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