Oncotarget

Research Papers:

Stellettin B induces apoptosis in human chronic myeloid leukemia cells via targeting PI3K and Stat5

Yali Chen, Qianxiang Zhou, Lei Zhang, Yuxu Zhong, Guanwei Fan, Zhe Zhang, Ran Wang, Meihua Jin, Yuling Qiu and Dexin Kong _

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Oncotarget. 2017; 8:28906-28921. https://doi.org/10.18632/oncotarget.15957

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Abstract

Yali Chen1,2, Qianxiang Zhou1,2, Lei Zhang1,2, Yuxu Zhong3, Guanwei Fan4, Zhe Zhang1, Ran Wang1, Meihua Jin1, Yuling Qiu1, Dexin Kong1,2

1Department of Biopharmaceutical Sciences, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China

2Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China

3State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

4Institute of Traditional Chinese Medicine Research, State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China

Correspondence to:

Dexin Kong, email: kongdexin@tmu.edu.cn

Yuling Qiu, email: qiuyuling@tmu.edu.cn

Keywords: stellettin B, K562, apoptosis, PI3K, combination

Received: October 20, 2016     Accepted: February 15, 2017    Published: March 07, 2017

ABSTRACT

Novel agents are still urgently expected for therapy of chronic myeloid leukemia (CML). The in vitro anti-leukemia activity of Stellettin B (Stel B), a triterpenoid we isolated from marine sponge Jaspis stellifera, on human CML K562 and KU812 cells was recently investigated. Stel B inhibited K562 and KU812 cell proliferation with IC50 as 0.035 μM and 0.95 μM respectively. While no obvious cell cycle arrest was observed, apoptosis was induced in K562 cells after Stel B treatment. The Stel B-induced apoptosis might be in mitochondrial pathway, with increase of Bad and Bax, decrease of Bcl-2 and activation of caspase-9. In addition, dose-dependent increase of reactive oxygen species (ROS) and loss of mitochondrial membrane potential (MMP) occurred. Meanwhile, Stel B inhibited phosphorylation of Stat5, expression of 4 PI3K catalytic isoforms, and phosphorylation of the downstream effectors including PDK1 and Akt, suggesting that inhibition against Stat5 and PI3K might be involved in the apoptosis-inducing effect. Combination of Stel B with Imatinib with ratio as IC50 Stel B : 5×IC50 Imatinib led to synergistic effect. Stel B might become a promising candidate for CML therapy alone or together with Imatinib.


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