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

Oncology Reports
Xiaoyang KongLigen Liu

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...Continue Reading

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Citations

Aug 31, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Michelle H LeeAshkan Emadi
Jul 4, 2019·International Journal of Molecular Sciences·Fu Ou-YangHsueh-Wei Chang
Dec 22, 2020·BioMed Research International·Zhenhua YinWenyi Kang
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Raedeh SaraeiSaeed Solali
May 9, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ze-Bo JiangElaine Lai-Han Leung
Jun 19, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Henry A AdeolaRashmi Bhardwaj

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