Selective Activation of ZAK β Expression by 3-Hydroxy-2-Phenylchromone Inhibits Human Osteosarcoma Cells and Triggers Apoptosis via JNK Activation

Autor: B Mahalakshmi Bharath, Yu-Lan Yeh, Chien-Yao Fu, Chih Yang Huang, Tso-Fu Wang, Marthandam Asokan Shibu, Yan-Shen Tseng, Ing-Shiow Lay, Wei Wen Kuo, Jaw-Ji Yang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
MAP Kinase Kinase 4
medicine.medical_treatment
ZAKβ
lcsh:Chemistry
0302 clinical medicine
Loss of Function Mutation
Protein Isoforms
lcsh:QH301-705.5
Spectroscopy
Membrane Potential
Mitochondrial
Caspase 3
Chemistry
Kinase
apoptosis
General Medicine
MAP Kinase Kinase Kinases
Up-Regulation
Computer Science Applications
Gain of Function Mutation
030220 oncology & carcinogenesis
Osteosarcoma
Signal Transduction
Antineoplastic Agents
Bone Neoplasms
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
3-Hydroxy-2-phenylchromone
Cell Line
Tumor
osteosarcoma
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
Loss function
Flavonoids
Chemotherapy
MAP kinase kinase kinase
Cell growth
Organic Chemistry
Cancer
medicine.disease
Enzyme Activation
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Apoptosis
Cancer research
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 9
International Journal of Molecular Sciences, Vol 21, Iss 3366, p 3366 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21093366
Popis: Although various advancements in radical surgery and neoadjuvant chemotherapy have been developed in treating osteosarcoma (OS), their clinical prognosis remains poor. A synthetic chemical compound, 3-hydroxylflavone, that is reported to regulate ROS production is known to inhibit human bone osteosarcoma cells. However, its role and mechanism in human OS cells remains unclear. In this study, we have determined the potential of 3-Hydroxy-2-phenylchromone (3-HF) against OS using human osteosarcoma (HOS) cells. Our previous studies showed that Zipper sterile-alpha-motif kinase (ZAK), a kinase member of the MAP3K family, was involved in various cellular events such as cell proliferation and cell apoptosis, and encoded two transcriptional variants, ZAK&alpha
and &beta
In this study, we show that 3-HF induces the expression of ZAK and thereby enhances cellular apoptosis. Using gain of function and loss of function studies, we have demonstrated that ZAK activation by 3-HF in OS cells is confined to a ZAK&beta
form that presumably plays a leading role in triggering ZAK&alpha
expression, resulting in an aggravated cancer apoptosis. Our results also validate ZAK&beta
as the predominant form of ZAK to drive the anticancer mechanism in HOS cells.
Databáze: OpenAIRE
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