Bortezomib Sensitizes Human Acute Myeloid Leukemia Cells to All-Trans-Retinoic Acid–Induced Differentiation by Modifying the RARα/STAT1 Axis
Meidan Ying,Xinglu Zhou,Like Zhong,Nengming Lin,Hui Jing,Peihua Luo,Xiaochun Yang,Hua Song,Bo Yang,Qiaojun He +9 more
TLDR
It is observed that bortezomib sensitized AML cells to ATRA-induced morphologic, biochemical, and functional changes, indicative of myeloid differentiation without cell death, which was the first to evaluate bortzomib and ATRA synergy in AML cell differentiation.Abstract:
All-trans-retinoic acid (ATRA) has held great promise for differentiation-based therapy but reportedly downregulates retinoic acid receptor-α (RARα) in a proteasome-dependent manner, which leads to decreased acute myeloid leukemia (AML) cell differentiation efficiency. Therefore, research strategies that seek to further sensitize cells to retinoids and extend the range of retinoid-affected myeloid malignancies beyond acute promyelocytic leukemia (APL) are key investigative avenues. Here, we show that bortezomib, the first proteasome inhibitor approved for newly diagnosed and relapsed multiple myeloma, exhibited strong synergism with ATRA to promote HL60 and NB4 AML cell differentiation. We observed that bortezomib sensitized AML cells to ATRA-induced morphologic, biochemical, and functional changes, indicative of myeloid differentiation without cell death. In addition, treatment of human leukemia HL60 xenografts with bortezomib and ATRA together did not increase bortezomib-induced progressive weight loss but resulted in significant tumor growth inhibition in addition to increased differentiation (P < 0.05). These enhanced differentiation effects were accompanied by RARα stabilization and STAT1 activation. Taken together, our study was the first to evaluate bortezomib and ATRA synergy in AML cell differentiation and to assess new opportunities for bortezomib and ATRA combination as a promising approach for future differentiation therapy.read more
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Overview of Proteasome Inhibitor-Based Anti-cancer Therapies: Perspective on Bortezomib and Second Generation Proteasome Inhibitors versus Future Generation Inhibitors of Ubiquitin-Proteasome System
Q. Ping Dou,Jeffrey A. Zonder +1 more
TL;DR: Targeting the immunoproteasome, ubiquitin E3 ligases, the 19S proteasome and deubiquitinases in pre-clinical studies represents possible directions for future generation inhibitors of ubiquit in-proteasome system in the treatment of MM and other cancers.
Journal ArticleDOI
The oxidation states of DJ-1 dictate the cell fate in response to oxidative stress triggered by 4-hpr: autophagy or apoptosis?
Ji Cao,Meidan Ying,Nan Xie,Guanyu Lin,Rong Dong,Jun Zhang,Hailin Yan,Xiaochun Yang,Qiaojun He,Bo Yang +9 more
TL;DR: ROS-mediated changes in the oxidation state of DJ-1 are involved in 4-HPR's effect on pushing autophagy down to apoptosis, and the results suggest thatDJ-1 might be a potent therapeutic target for cancer treatment.
Journal ArticleDOI
The success and the challenge of all-trans retinoic acid in the treatment of cancer
Xiaoling Ni,Guohua Hu,Xun Cai +2 more
TL;DR: All-trans retinoic acid (ATRA), an active metabolite of vitamin A, plays important roles in cell proliferation, cell differentiation, apoptosis, and embryonic development and its role in cancer treatment is discussed.
Journal ArticleDOI
Ubiquitin-dependent degradation of CDK2 drives the therapeutic differentiation of AML by targeting PRDX2
Meidan Ying,Xuejing Shao,Hui Jing,Yujia Liu,Xiaotian Qi,Ji Cao,Yingqian Chen,Senfeng Xiang,Hua Song,Ronggui Hu,Guoqing Wei,Bo Yang,Qiaojun He +12 more
TL;DR: This work unveils a new role for cyclin-dependent kinase 2 (CDK2) in blocking myeloid differentiation in AML and uncovers the biological function of the CDK2-PRDX2 axis in blocking AML differentiation.
Journal ArticleDOI
Hyperoside, a Flavonoid Compound, Inhibits Proliferation and Stimulates Osteogenic Differentiation of Human Osteosarcoma Cells
TL;DR: It is demonstrated that hyperoside inhibits the proliferation of osteosarcoma cells by inducing G0/G1 arrest in the cell cycle, without causing obvious cell death, and the possible potential forhyperoside treatment as a future therapeutic approach for osteosARcoma differentiation therapy is assessed.
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