ArticleActa pharmacologica Sinica2012
Perifosine induces protective autophagy and upregulation of ATG5 in human chronic myelogenous leukemia cells in vitro.
Article in Acta pharmacologica Sinica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- [Imatinib mesylate for chronic myeloid leukemia: in patients with initial treatment versus those with Recombinant Human IFN-α2b treatment failure].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2015Trial
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- BRMS1L promotes chemotherapy sensitivity by inhibiting autophagy in breast cancer.Frontiers in genetics · 2025Article
- The Question of Survival or Death: What Is the Role of Autophagy in Acute Myeloid Leukemia (AML)?International journal of hematology-oncology and stem cell research · 2022Review
- The roles of KLHL family members in human cancers.American journal of cancer research · 2022Review
- Dual Akt and Bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines.Molecular biology reports · 2021Article
- Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers.Cancers · 2021Review
- Targeting autophagy-related protein kinases for potential therapeutic purpose.Acta pharmaceutica Sinica. B · 2020Review
- Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.Frontiers in pharmacology · 2020Review
- Xanthohumol, a Prenylated Flavonoid from Hops, Induces Caspase-Dependent Degradation of Oncoprotein BCR-ABL in K562 Cells.Antioxidants (Basel, Switzerland) · 2019Article
- Akt targeting as a strategy to boost chemotherapy efficacy in non-small cell lung cancer through metabolism suppression.Scientific reports · 2017Article
- Loss of HSulf-1: The Missing Link between Autophagy and Lipid Droplets in Ovarian Cancer.Scientific reports · 2017Article
- Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer.Cellular oncology (Dordrecht, Netherlands) · 2017Review
- Article
- Proteasome inhibitor MG-132 enhances histone deacetylase inhibitor SAHA-induced cell death of chronic myeloid leukemia cells by an ROS-mediated mechanism and downregulation of the Bcr-Abl fusion protein.Oncology letters · 2015Article
- Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in chronic myeloid leukemia.International journal of oncology · 2014Article
- Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy.Haematologica · 2014Review
- The short chain cell-permeable ceramide (C6) restores cell apoptosis and perifosine sensitivity in cultured glioblastoma cells.Molecular biology reports · 2013Article
- Autophagy in blood cancers: biological role and therapeutic implications.Haematologica · 2013Review
- Autophagy modulation as a target for anticancer drug discovery.Acta pharmacologica Sinica · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe efficacy of the Akt inhibitor perifosine against chronic myeloid leukemia (CML) cells and its mechanisms of action are unknown. In this study, the cytotoxic effects of perifosine on CML and acute myeloid leukemia (AML) cell lines were compared to elucidate the mechanisms underlying the differences.
methodsHuman AML cell lines Kasumi-1 and HL-60, and the CML cell line K562 were used. Cell viability was quantitated using MTT assay. Apoptosis was determined using Annexin V-FITC/propidium iodide and Hoechst staining, which were followed by flow cytometry and fluorescence microscopy analysis, respectively. Caspase pathway activation and the expression of autophagy-related genes were examined using Western blot. Autophagy was studied using electron microscopy, the acridine orange staining method, and GFP-LC3 was examined with fluorescence microscopy.
resultsIn contrast to AML cell lines, the CML cell lines K562 and K562/G (an imatinib-insensitive CML cell line) were resistant to perifosine (2.5-20 μmol/L) in respect to inhibiting cell growth and inducing apoptosis. Perifosine (2.5, 5, and 10 μmol/L) inhibited Akt and its phosphorylation in AML cells, but not in CML cells. Treatment with perifosine (20 μmol/L) resulted in autophagy in CML cells as shown by the increased formation of acidic vesicular organelles and the accumulation of LC3-II. Treatment of CML cells with perifosine (5, 10, and 20 μmol/L) dose-dependently upregulated AGT5, but not Beclin 1 at the protein level. Furthermore, inhibition of autophagy by chloroquine (40 nmol/L) significantly suppressed the cell growth and induced apoptosis in CML cells treated with perifosine (20 μmol/L).
conclusionOur results show that CML cell lines were resistant to the Akt inhibitor perifosine in vitro, which is due to perifosine-induced protective autophagy and upregulation of ATG5.
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