Oncotarget

Research Papers:

ZGDHu-1 promotes apoptosis of mantle cell lymphoma cells

Liannv Qiu _, Zhenni Wang, Sufeng Chen, Weixiao Hu, Qiang Huang and Yonglie Zhou

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Oncotarget. 2017; 8:11659-11675. https://doi.org/10.18632/oncotarget.14274

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Abstract

Liannv Qiu1, Jinlin Liu1, Zhenni Wang1, Sufeng Chen1, Weixiao Hu2, Qiang Huang3, Yonglie Zhou1

1Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China

2College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, Zhejiang, China

3Department of Hematology, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China

Correspondence to:

Liannv Qiu, email: [email protected]

Yonglie Zhou, email: [email protected]

Keywords: N, N’-di-(m-methylphenyi)-3, 6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide; mantle cell lymphoma; cell cycle; apoptosis; NF-κB

Received: April 09, 2016    Accepted: November 30, 2016    Published: December 27, 2016

ABSTRACT

Mantle cell lymphoma (MCL) is a well-defined aggressive Non-Hodgkin-lymphoma with short survival rates and remains incurable to date. Previously, we demonstrated the antitumor activity of ZGDHu-1(N, N’-di-(m-methylphenyi)-3, 6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide) in chronic lymphocytic leukemia. In this study, ZGDHu-1 shows potent anti-lymphoma activity in MCL cells. ZGDHu-1 significantly induces cell cycle G2/M phase arrest and apoptosis in MCL cells. ZGDHu-1 reduces the protein levels of Mcl-1, Bcl-XL and cyclin D1. Importantly, ZGDHu-1 inhibits TNFα-induced IkBa phosphorylation, p65 nuclear translocation and NF-kB downstream target gene expression in MCL cells. MCL samples expressing high levels of Bcl-2 and high Bcl-2/Bax ratios tend to be less effective to ZGDHu-1. Together, these results suggest that ZGDHu-1 could inhibit the NF-kB signaling pathway partly, which may lead to the suppression of cell proliferation and the induction of apoptosis in MCL cells. Thus, our studies provide evidence of the potential of ZGDHu-1 in treating mantle cell lymphoma.


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