Azacytidine sensitizes acute myeloid leukemia cells to arsenic trioxide by up-regulating the arsenic transporter aquaglyceroporin 9

Chau, David; Ng, Karen Ka Man; Chan, Thomas S. Y.; Cheng, Y.Y.; Fong, Bonnie Mei-Wah; Tam, Sidney; Kwong, Yok–Lam; Tse, Eric

doi:10.1186/s13045-015-0143-3

Cited by 27 publications

(24 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we used a concentration of ATO (6 μ M) to construct an in vitro liver cell injury model. A relative high concentration of ATO in anti-blood tumor researches is 6 μ M, 40 , 41 but commonly used in solid tumor researches. 42 , 43 , 44 By in vitro and in vivo assays, we demonstrated the protective effects of metformin on ATO-induced liver injury.…”

Section: Discussionmentioning

confidence: 99%

Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I

et al. 2017

View full text Add to dashboard Cite

Arsenic trioxide (ATO) is a well-accepted chemotherapy agent in managing promyelocytic leukemia. ATO often causes severe health hazards such as hepatotoxicity, dermatosis, neurotoxicity, nephrotoxicity and cardiotoxicity. The production of reactive oxygen species, (ROS) play a significant role in ATO-induced hepatotoxicity. The oral hypoglycemic drug, metformin, is considered to be a potential novel agent for chemoprevention in the treatment of cancer. Moreover, metformin has also been shown to have hepatoprotective effects. In the present study, we demonstrated that metformin protected normal hepatocytes from ATO-induced apoptotic cell death in vitro and in vivo. Gene expression screening revealed that glucose metabolism might be related to the metformin-induced protective effect on ATO-treated AML12 cells. The metformin-promoted or induced glycolysis was not responsible for the protection of AML12 cells from ATO-induced apoptotic cell death. Instead, metformin increased the intracellular NADH/NAD+ ratio by inhibiting mitochondrial respiratory chain complex I, further decreasing the intracellular ROS induced by ATO. Treatment with low glucose or rotenone, a mitochondrial respiratory chain complex I inhibitor, also protected AML12 cells from ATO-induced apoptotic cell death. We show for the first time that metformin protects the hepatocyte from ATO by regulating the mitochondrial function. With its properties of chemoprevention, chemosensitization and the amelioration of liver damage, metformin has great prospects for clinical application other than type 2 diabetes mellitus (T2DM).

show abstract

Section: Discussionmentioning

confidence: 99%

Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I

et al. 2017

View full text Add to dashboard Cite

show abstract

“… 30 , 31 In some recent studies, AZT exhibited significant synergistic therapeutic with other drugs for tumors in a safe dosage range. 32 – 34 Chau et al 35 suggested that the combination of azacytidine with As 2 O 3 would be a logical drug combination for treatment of AML in the future. Wang et al 36 reported that the combination of AZT with emodin could co-inhibit the proliferation of leukemia KG-1a cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of the combination of As<sub>2</sub>O<sub>3</sub> and AZT on proliferation inhibition and apoptosis induction of hepatoma HepG2 cells following silencing of Egr-1

Zhao

Wang

Liu

et al. 2018

OTT

View full text Add to dashboard Cite

ContextPrevious studies have demonstrated that 3′-azido-3′-deoxythymidine (AZT) and arsenic trioxide (As2O3), traditional chemotherapy agents, can synergically inhibit the growth of hepatocellular carcinoma cells. However, the molecular mechanisms underlying As2O3 and AZT anti-hepatoma activity are unknown.ObjectiveThis study aimed to investigate the role of early growth response protein 1 (Egr-1) in the process of As2O3 combined with AZT inhibiting proliferation and inducing apoptosis of human hepatocellular carcinoma HepG2 cells, and explore the possible mechanism.Materials and methodsThe expression of Egr-1 was silenced using siRNA, and then HepG2 cells were treated with As2O3 (2 μM) and AZT (20 μM). The rates of cell inhibition and apoptosis were determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) method and flow cytometry, respectively. The mRNA and protein expression of p53, caspase-3, and Egr-1 were detected by real-time quantitative polymerase chain reaction and Western blotting, respectively.ResultsThe inhibitory rate of As2O3 (2 μM) combined with AZT (20 μM) on proliferation of HepG2 cells was significantly higher than that of As2O3 alone. The combination index (CI) values were 0.2

show abstract

“…As indicated in lung cancer and glioma, BSO was shown to enhance the ATOinduced anticancer effect by mediating ROS generation in AML cells [87] and other leukemic/lymphoma cells [88], suggesting that combined ATO-BSO treatment would be one of the attractive alternative therapies for cancer treatment. It has also been reported that combined treatment with ATO and dichloroacetate [89], azacytidine [90], rapamycin [91], and aclacino-…”

Section: Acute Myeloid Leukemia (Aml)mentioning

confidence: 95%

Arsenic-Based Anticancer-Combined Therapy: Novel Mechanism Inducing Apoptosis of Cancer Cells

Ota¹,

Wahiduzzaman²,

Hosokawa³

2018

Current Understanding of Apoptosis - Programmed Cell Death

View full text Add to dashboard Cite

Arsenic, known as both a naturally occurring toxic element and a traditionally used drug, has caught a great deal of attention from worldwide people due to its curable anticancer effect in patients with acute promyelocytic leukemia (APL). Among the arsenicals, arsenic trioxide (ATO) has been the most widely used anticancer drug. Since ATO exerts an anticancer effect by mediating apoptosis, numerous studies have made efforts to uncover the molecular mechanisms by which ATO activates and/or mediates the apoptotic signaling pathway in cancer cells. Recent advances in cancer therapeutics have led to a paradigm shift away from the traditional cytotoxic drugs toward the targeting of proteins closely associated with driving the cancer phenotype. Here, we discuss novel current arsenic-based combination therapies to treat cancer in both clinical and experimental settings. We also discuss the novel molecular mechanism underlying apoptosis induced by the combined therapies.

show abstract

Azacytidine sensitizes acute myeloid leukemia cells to arsenic trioxide by up-regulating the arsenic transporter aquaglyceroporin 9

Cited by 27 publications

References 30 publications

Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I

Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I

Effects of the combination of As<sub>2</sub>O<sub>3</sub> and AZT on proliferation inhibition and apoptosis induction of hepatoma HepG2 cells following silencing of Egr-1

Arsenic-Based Anticancer-Combined Therapy: Novel Mechanism Inducing Apoptosis of Cancer Cells

Contact Info

Product

Resources

About