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Arsenic Trioxide Controls the Fate of the PML-RARα Oncoprotein by Directly Binding PML
It is shown that arsenic binds directly to cysteine residues in zinc fingers located within the RBCC domain of PML-RARα and PML, identifying PML as a direct target of As2O3 and providing new insights into the drug’s mechanism of action and its specificity for APL.
Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia
- Lan Wang, Guang-Biao Zhou, Zhu Chen
- BiologyProceedings of the National Academy of Sciences
- 25 March 2008
ITA causes intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor α (RARα) oncoprotein, stronger reprogramming of myeloid differentiation regulators, and enhanced G1/G0 arrest in APL cells through hitting multiple targets compared with the effects of mono- or biagents.
AML1-ETO and C-KIT mutation/overexpression in t(8;21) leukemia: implication in stepwise leukemogenesis and response to Gleevec.
- Yue-Ying Wang, Guang-Biao Zhou, Saijuan Chen
- BiologyProceedings of the National Academy of Sciences…
- 25 January 2005
The data strongly suggest that t(8;21) AML follows a stepwise model in leukemogenesis, i.e., AE represents the first, fundamental genetic hit to initiate the disease, whereas activation of the C-KIT pathway may be a second but also crucial hit for the development of a full-blown leukemia.
Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia
- Jiong Hu, Yuan-fang Liu, Zhu Chen
- MedicineProceedings of the National Academy of Sciences
- 3 March 2009
The results demonstrate the high efficacy and minimal toxicity of ATRA/ATO treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for de novo APL.
Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21) leukemia in vitro and in vivo.
The results suggest that oridonin may be a potential antileukemia agent that targets AE oncoprotein at residue D188 with low adverse effect, and may be helpful for the treatment of patients with t(8;21) AML.
From an old remedy to a magic bullet: molecular mechanisms underlying the therapeutic effects of arsenic in fighting leukemia.
- Saijuan Chen, Guang-Biao Zhou, Xiao-Wei Zhang, J. Mao, H. de Thé, Zhu Chen
- Biology, ChemistryBlood
- 16 June 2011
The successful revival of arsenic in acute promyelocytic leukemia, together with modern mechanistic studies, has thus allowed a new paradigm to emerge in translational medicine.
Cancerous inhibitor of PP2A is targeted by natural compound celastrol for degradation in non-small-cell lung cancer.
Celastrol binds CIP2A and enhances CIP2A-CHIP interaction, leading to ubiquitination/degradation of CIP2A and inhibition of lung cancer cells in vitro and in vivo. Celastrol potentiates cisplatin's…
Overexpression and Small Molecule-Triggered Downregulation of CIP2A in Lung Cancer
It is found that a natural compound, rabdocoetsin B which is extracted from a Traditional Chinese Medicinal herb Rabdosia coetsa, could induce down-regulation of CIP2A and inactivation of Akt pathway, and inhibit proliferation and induce apoptosis in a variety of lung cancer cells.
The natural compound magnolol inhibits invasion and exhibits potential in human breast cancer therapy
Results indicate that Mag suppresses tumor invasion by inhibiting MMP-9 through the NF-κB pathway, an enzyme critical to tumor invasion.
The Aryl hydrocarbon receptor mediates tobacco-induced PD-L1 expression and is associated with response to immunotherapy
It is demonstrated that tobacco smoke enables lung epithelial cells to escape from adaptive immunity to promote tumorigenesis, and AhR predicts the response to immunotherapy and represents an attractive therapeutic target.