Midkine inhibitor (iMDK) induces apoptosis of primary effusion lymphoma via G2/M cell cycle arrest
Issued Date
2022-05-01
Resource Type
ISSN
01452126
eISSN
18735835
Scopus ID
2-s2.0-85126545200
Pubmed ID
35316715
Journal Title
Leukemia Research
Volume
116
Rights Holder(s)
SCOPUS
Bibliographic Citation
Leukemia Research Vol.116 (2022)
Suggested Citation
Ueno M., Kariya R., Gunya S., Cheevapruk K., Okada S. Midkine inhibitor (iMDK) induces apoptosis of primary effusion lymphoma via G2/M cell cycle arrest. Leukemia Research Vol.116 (2022). doi:10.1016/j.leukres.2022.106826 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83752
Title
Midkine inhibitor (iMDK) induces apoptosis of primary effusion lymphoma via G2/M cell cycle arrest
Author(s)
Other Contributor(s)
Abstract
Primary effusion lymphoma (PEL) is an aggressive B-cell non-Hodgkin lymphoma in immunocompromised individuals such as AIDS patients. PEL shows a poor prognosis (median survival time < 6 months) compared with other AIDS-related lymphomas, and is generally resistant to conventional treatments. Novel drugs for PEL treatment are required. Midkine inhibitor (iMDK) was previously found to suppress midkine protein expression. Interestingly, iMDK suppressed cell proliferation in PEL cell lines in a time- and dose-dependent manner, regardless of midkine gene expression. We examined the mechanism of iMDK on PEL. Importantly, iMDK strongly induced cell cycle arrest at the G2/M phase within 12 h of incubation and suppressed the p-CDK1 protein level, which is associated with the cell cycle checkpoint at G2/M, resulting in mitotic catastrophe with observation of multipolar division. After mitotic catastrophe, iMDK-treated PEL showed apoptosis with caspase-3, − 8, and − 9 activation at 24 h incubation. However, iMDK showed no effects on viral protein-activated signaling pathways such as JAK-STAT, PI3K-Akt and NF-κB, and HHV-8/KSHV gene expression in PEL. These results indicate that iMDK is a novel CDK1 inhibitor and a promising lead compound for PEL chemotherapy treatment.