ZGDHu-1 and fludarabine have a synergistic effect on apoptosis of chronic lymphocytic leukemia cells

Qiu, Liannv; Liu, Jinlin; Wang, Zhenni; Hu, Wei‐Xiao; Huang, Qiang; Zhou, Yongchao

doi:10.3892/or.2015.4115

Cited by 6 publications

(5 citation statements)

References 28 publications

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“…ZGDHu-1 [N,N ′ -di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide] is a proteasome inhibitor and has been reported to exhibit antitumor activity [ 64 , 65 ]. A study has recently been conducted to assess whether this drug has a synergistic effect with fludarabine and mediates apoptosis in CLL cells [ 66 ]. CLL cell-specific apoptosis occurred through the mitochondrial pathway as normal cells remained unaffected.…”

Section: List Of Therapeutic Compounds Targeting Mitochondrial Biomentioning

confidence: 99%

Targeting Mitochondrial Bioenergetics as a Therapeutic Strategy for Chronic Lymphocytic Leukemia

Chowdhury

Banerji

2018

Oxidative Medicine and Cellular Longevity

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Altered cellular metabolism is considered a hallmark of cancer and is fast becoming an avenue for therapeutic intervention. Mitochondria have recently been viewed as an important cellular compartment that fuels the metabolic demands of cancer cells. Mitochondria are the major source of ATP and metabolites necessary to fulfill the bioenergetics and biosynthetic demands of cancer cells. Furthermore, mitochondria are central to cell death and the main source for generation of reactive oxygen species (ROS). Overall, the growing evidence now suggests that mitochondrial bioenergetics, biogenesis, ROS production, and adaptation to intrinsic oxidative stress are elevated in chronic lymphocytic leukemia (CLL). Hence, recent studies have shown that mitochondrial metabolism could be targeted for cancer therapy. This review focuses the recent advancements in targeting mitochondrial metabolism for the treatment of CLL.

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Section: List Of Therapeutic Compounds Targeting Mitochondrial Biomentioning

confidence: 99%

Targeting Mitochondrial Bioenergetics as a Therapeutic Strategy for Chronic Lymphocytic Leukemia

Chowdhury

Banerji

2018

Oxidative Medicine and Cellular Longevity

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“…Thus, reducing the toxicity of fludarabine by reducing its dose and the identification of novel candidate drugs are warranted. In our study, it was revealed that ZGDHu-1 and fludarabine had a synergistic effect on the cytotoxicity and apoptosis of CLL cells, and this effect was also dependent on the loss of ΔΨm, PS translocation and ROS accumulation ( 14 ). The combination also significantly induced the cleavage of caspase-3 and significantly decreased anti-apoptotic Bcl-2 expression in CLL cells ( 14 ).…”

Section: Anti-leukemic Activity Of Zgdhu-1mentioning

confidence: 89%

“…Therefore, the combination of ZGDHu-1 and fludarabine may be useful for the maintenance therapy of patients with CLL, as it can sensitize CLL cells to low doses of fludarabine without increasing the risk of long-term side effects on the immune system or other opportunistic infections ( 14 ). However, numerous important questions remain unresolved regarding what type of biomarkers that distinguish lymphoid malignancies will respond to ZGDHu-1 as a monotherapy or combination with other chemotherapy drugs, and whether relapsed or refractory patients with CLL are sensitive to the ZGDHu-1.…”

Section: Anti-leukemic Activity Of Zgdhu-1mentioning

confidence: 99%

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ZGDHu‑1 for cancer therapy (Review)

et al. 2017

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N,N'-di-(m-methylphenyl)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1) is a novel tetrazine derivative that was initially designed and produced by Professor W.X. Hu, and which has been reported by our group to exhibit antitumor activity. Accumulating evidence suggests that the anticancer mechanisms of ZGDHu-1 may be involved indifferent biological activities, particularly in acute myeloid leukemia (AML) cells. At a high concentration, ZGDHu-1 has been demonstrated to inhibit the proliferation of the leukemia cells by arresting the cell cycle at the G2/M phase, and by inducing cell apoptosis via inducing the accumulation of reactive oxygen species, the translocation of phosphatidylserine across the plasma membrane and the loss of mitochondrial membrane potential. Furthermore, at a low concentration, it was demonstrated to induce the differentiation and degrade the AML1-eight-twenty-one fusion protein in AML cells. Finally, results from a previous study indicate that ZGDHu-1 is a potential proteasome inhibitor. Overall, our preliminary research suggests that ZGDHu-1 may be a promising anticancer drug; however, further research is warranted to identify the exact drug target and potential clinical application in leukemia cells or solid tumors. In the present review, the application of ZGDHu-1 in cancer research, in addition to the specific underlying targets of ZGDHu-1, are discussed.

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“…Antitumor effects include anti-leukemia cells, proliferation and suppression of pancreatic cancer cells. Potential therapeutic effects include promotion of apoptosis of chronic lymphocytic leukemia (CLL) cells for treatment of lung cancer, a synergistic effect on apoptosis of CLL cells with fludarabine, and excellent results in treatment of acute myeloid leukemia (3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of ZGDHu-1 Nanoparticles

Shi¹,

Liu²,

Wu³

et al. 2021

Dissolution Technol.

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The purpose of this study was to establish the preparation process of ZGDHu-1 nanoparticles and to study its physicochemical properties. The nanoparticles were prepared using a high-pressure homogenization method. Natural phospholipid and soybean oil were used as drug carriers, and Cremophor EL was used as surfactant. The resulting nanoparticles had a spherical shape, with a mean ± SD particle size of 106.8 ± 15.9 nm, polydispersity index (PDI) of 0.136 ± 0.011, zeta potential of -63.97 ± 3.57 mV, encapsulation efficiency of 86.95%, and in vitro cumulative release rate of 84.67% in 24 hours. The nanoparticle preparation process was simple and reproducible. The nanoparticles had good physicochemical properties and in vitro release was improved by increasing solubility. This study provides a method for improving in vitro release for development of ZGDHu-1 nanoparticle formulations.

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ZGDHu-1 and fludarabine have a synergistic effect on apoptosis of chronic lymphocytic leukemia cells

Cited by 6 publications

References 28 publications

Targeting Mitochondrial Bioenergetics as a Therapeutic Strategy for Chronic Lymphocytic Leukemia

Targeting Mitochondrial Bioenergetics as a Therapeutic Strategy for Chronic Lymphocytic Leukemia

ZGDHu‑1 for cancer therapy (Review)

Preparation and Characterization of ZGDHu-1 Nanoparticles

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