A natural small molecule induces megakaryocytic differentiation and suppresses leukemogenesis through activation of PKCδ/ERK1/2 signaling pathway in erythroleukemia cells

Autor: Li Chen, Yong Hu, Jue Yang, Song Jingrui, Qing Rao, Qiu Jianfei, Wei Gu, Juan Chen, Qun Long, Xiao-Jiang Hao, Yanmei Li, Yongqiang Zhang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cell cycle checkpoint
Carcinogenesis
MAP Kinase Signaling System
Kaempferol 3-O-α-L-(4″-E-p-coumaroyl) rhamnoside
Cyclocarya paliurus
Apoptosis
RM1-950
Models
Biological
Flow cytometry
Small Molecule Libraries
03 medical and health sciences
Inhibitory Concentration 50
0302 clinical medicine
medicine
Humans
Viability assay
Glycosides
Kaempferols
Pharmacology
Leukemia
medicine.diagnostic_test
Cell growth
Chemistry
Plant Extracts
Cell Differentiation
General Medicine
Cell Cycle Checkpoints
Megakaryocytic differentiation
PKCδ/ERK1/2 signaling pathway
Cell biology
Plant Leaves
Protein Kinase C-delta
030104 developmental biology
030220 oncology & carcinogenesis
Phosphorylation
Therapeutics. Pharmacology
Signal transduction
K562 Cells
Megakaryocytes
K562 cells
Erythroleukemia
Zdroj: Biomedicine & Pharmacotherapy, Vol 118, Iss, Pp-(2019)
ISSN: 0753-3322
Popis: Kaempferol-3-O-rhamnoside (KOR) has multiple potency involved in anti-cancer, anti-inflammatory and antibacterial actions. However, the potential roles of KOR and the analogues isolated from the leaves of Cyclocarya paliurus in anti-erythroleukemia remain unclear. In the present study, KOR and the two analogues (Kaempferol-3-O-(4″-O-acetyl-a-L-rhamnopyranoside) (KLR) and (kaempferol-3-O-α-L-(4″-E-p-coumaroyl) rhamnoside) (KCR) were isolated from leaves of Cyclocarya paliurus. Cell viability assay showed that KCR exerted an excellent anti-erythroleukemia activity. We observed that KCR not only significantly increased the percentage of G2 phase and apoptotic cells compared with control group, but also induced megakaryocytic differentiation in HEL and K562 cells by flow cytometry, indicating that KCR might inhibit cell proliferation through inducing differentiation-mediated apoptosis and cell cycle arrest. Mechanism investigation revealed that KCR treatment obviously increased phosphorylation levels of PKCδ and ERK1/2 as well as GATA1 expression. Taken together, these findings demonstrate that KCR induces megakaryocytic differentiation and suppresses leukemogenesis at least partly through activation of PKCδ/ERK1/2 signaling pathway in erythroleukemia cells. KCR may also serve as a promising natural compound for human erythroleukemia treatment.
Databáze: OpenAIRE
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