Doxorubicin induces ZAKα overexpression with a subsequent enhancement of apoptosis and attenuation of survivability in human osteosarcoma cells.

Abstract

Human osteosarcoma (OS) is a malignant cancer of the bone. It exhibits a characteristic malignant osteoblastic transformation and produces a diseased osteoid. A previous study demonstrated that doxorubicin (DOX) chemotherapy decreases human OS cell proliferation and might enhance the relative RNA expression of ZAK. However, the impact of ZAKα overexpression on the OS cell proliferation that is inhibited by DOX and the molecular mechanism underlying this effect are not yet known. ZAK is a protein kinase of the MAPKKK family and functions to promote apoptosis. In our study, we found that ZAKα overexpression induced an apoptotic effect in human OS cells. Treatment of human OS cells with DOX enhanced ZAKα expression and decreased cancer cell viability while increasing apoptosis of human OS cells. In the meantime, suppression of ZAKα expression using shRNA and inhibitor D1771 both suppressed the DOX therapeutic effect. These findings reveal a novel molecular mechanism underlying the DOX effect on human OS cells. Taken together, our findings demonstrate that ZAKα enhances the apoptotic effect and decreases cell viability in DOX-treated human OS cells.

• Authors: Chien-Yao Fu, Yan-Shen Tseng, Ming-Cheng Chen, Hsi-Hsien Hsu, Jaw-Ji Yang, Chuan-Chou Tu, Yueh-Min Lin, Vijaya Padma Viswanadha, Wei-Wen Kuo, Chih-Yang Huang
• Journal: Environmental toxicology (Environ Toxicol) Vol. 33 Issue 2 Pg. 191-197 (Feb 2018) ISSN: 1522-7278 [Electronic] United States
• PMID: 29105997 (Publication Type: Journal Article)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Antibiotics, Antineoplastic
• NF-kappa B
• RNA, Small Interfering
• bcl-X Protein
• Doxorubicin
• Protein Kinases
• MAP Kinase Kinase Kinases
• MAP3K20 protein, human
• Caspase 3

Topics

• Antibiotics, Antineoplastic (toxicity)
• Apoptosis (drug effects)
• Bone Neoplasms (metabolism, pathology)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Doxorubicin (toxicity)
• Humans
• MAP Kinase Kinase Kinases
• NF-kappa B (metabolism)
• Osteosarcoma (metabolism, pathology)
• Protein Kinases (chemistry, genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• bcl-X Protein (metabolism)