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Plumbagin enhances TRAIL-induced apoptosis of human leukemic Kasumi‑1 cells through upregulation of TRAIL death receptor expression, activation of caspase-8 and inhibition of cFLIP
- Source :
- Oncology reports. 37(6)
- Publication Year :
- 2016
-
Abstract
- Although the patients with t(8;21) acute myeloid leukemia (AML) have a favorable prognosis compared with other non-acute promyelocytic leukemia AML patients, only ~50% patients with this relatively favorable subtype can survive for 5 years and refractory/relapse is common in clinical practice. So it is necessary to find novel agents to treat this type of AML. In this study, the effects and the mechanisms of plumbagin and recombinant soluble tumor necrosis factor‑α-related apoptosis-inducing ligand (rsTRAIL) on leukemic Kasumi‑1 cells were primarily investigated. Plumbagin and/or rsTRAIL could significantly inhibit the growth of Kasumi‑1 cells and induce apoptosis in vitro and in vivo. Plumbagin enhanced TRAIL-induced apoptosis of Kasumi‑1 cells in association with mitochondria damage, caspase activation, upregulation of death receptors (DRs) and decreased cFLIP expression. The effects of plumbagin on the expression of DR5, Bax and cFLIP could be partially abolished by the reactive oxygen species (ROS) scavenger NAC. Glutathione (GSH) depletion by plumbagin increased the production of ROS. In vivo, there was no obvious toxic pathologic change in the heart, liver and kidney tissues in any of the groups. Comparing with the control mice, a significantly increased number of apoptotic cells were observed in the combined treated mice by flow cytometry. Plumbagin also increased the expression of DR4 and DR5 in cells of xenograft tumors. Collectively, our results suggest that both plumbagin and rsTRAIL could be used as a single agent or synergistical agents to induce apoptosis of leukemic Kasumi‑1 cells in vitro and in vivo.
- Subjects :
- 0301 basic medicine
Cancer Research
Receptor expression
CASP8 and FADD-Like Apoptosis Regulating Protein
Apoptosis
Biology
Caspase 8
TNF-Related Apoptosis-Inducing Ligand
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Downregulation and upregulation
In vivo
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
Animals
Humans
Cell Proliferation
Gene Expression Regulation, Leukemic
Myeloid leukemia
General Medicine
Plumbagin
Molecular biology
Glutathione
Xenograft Model Antitumor Assays
Recombinant Proteins
Mitochondria
Leukemia, Myeloid, Acute
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
Cancer research
Tumor necrosis factor alpha
Reactive Oxygen Species
Naphthoquinones
Subjects
Details
- ISSN :
- 17912431
- Volume :
- 37
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Oncology reports
- Accession number :
- edsair.doi.dedup.....c3d6b13dd7db57063c74e06ad2cce6a0