Dose-dependent effects of selenite (Se4+) on arsenite (As3+)-induced apoptosis and differentiation in acute promyelocytic leukemia cells

Wang, Shaohe; Geng, Zhirong; Shi, Nan; Li, X; Wang, Z

doi:10.1038/cddis.2014.563

Cited by 21 publications

(4 citation statements)

References 39 publications

(77 reference statements)

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“…While we have been pursuing our work, a parallel study has reported abrogation of PML/RARα protein expression following selenite treatment [33]. Consistent with this study, we also provide evidence for abrogation of PML/RARα expression by selenite alone in a different experimental set up.…”

Section: Discussionsupporting

confidence: 86%

Selenite promotes all-trans retinoic acid-induced maturation of acute promyelocytic leukemia cells

et al. 2016

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Selective targeting of the PML/RARα oncoprotein demonstrates a successful molecular targeted therapy in acute promyelocytic leukemia (APL) with a typical t(15:17) chromosomal translocation. The zinc-thiolate coordination is critical for structural stability of zinc finger proteins, including the PML moiety of PML/RARα. Based on the known interaction of redox-active selenium compounds with thiolate ligands of zinc, we herein have investigated the abrogatory effects of selenite alone or in combination with all-trans retinoic acid on PML/RARα and the possible effects on differentiation in these cells. At pharmacological concentrations, selenite inhibited the proliferation and survival of APL originated NB4 cells. In combination with ATRA, it potentiated the differentiation of NB4 cells without any differentiating effects of its own as a single agent. Concordant with our hypothesis, PML/RARα oncoprotein expression was completely abrogated by selenite. Increased expression of RAR, PU.1 and FOXO3A transcription factors in the combined treatment suggested the plausible basis for increased differentiation in these cells. We show that selenite at clinically achievable dose targets PML/RARα oncoprotein for degradation and potentiates differentiation of promyelocytic leukemic cells in combination with ATRA. The present investigation reveals the hitherto unknown potential of selenite in targeted abrogation of PML/RARα in APL cells with prospective therapeutic value.

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Section: Discussionsupporting

confidence: 86%

Selenite promotes all-trans retinoic acid-induced maturation of acute promyelocytic leukemia cells

et al. 2016

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“…After 72 h of treatment, 1.6 μM BKM120 increased the percentage of DCF-positive cells, indicating an increase of cellular ROS (Fig. 2 B) 37 . Compared with control, the effect of 9.6 μM olaparib on the accumulation of cellular ROS was not obvious.…”

Section: Resultsmentioning

confidence: 89%

BKM120 sensitizes BRCA-proficient triple negative breast cancer cells to olaparib through regulating FOXM1 and Exo1 expression

Liu

Wang

Zhang

et al. 2021

Sci Rep

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Poly (ADP-ribose) polymerase (PARP) inhibitors offer a significant clinical benefit for triple-negative breast cancers (TNBCs) with BRCA1/2 mutation. However, the narrow clinical indication limits the development of PARP inhibitors. Phosphoinositide 3-kinase (PI3K) inhibition sensitizes BRCA-proficient TNBC to PARP inhibition, which broadens the indication of PARP inhibitors. Previously researches have reported that PI3K inhibition induced the defect of homologous recombination (HR) mediated repair by downregulating the expression of BRCA1/2 and Rad51. However, the mechanism for their synergistic effects in the treatment of TNBC is still unclear. Herein, we focused on DNA damage, DNA single-strand breaks (SSBs) repair and DNA double-strand breaks (DSBs) repair three aspects to investigate the mechanism of dual PI3K and PARP inhibition in DNA damage response. We found that dual PI3K and PARP inhibition with BKM120 and olaparib significantly reduced the proliferation of BRCA-proficient TNBC cell lines MDA-MB-231 and MDA231-LM2. BKM120 increased cellular ROS to cause DNA oxidative damage. Olaparib resulted in concomitant gain of PARP1, forkhead box M1 (FOXM1) and Exonuclease 1 (Exo1) while inhibited the activity of PARP. BKM120 downregulated the expression of PARP1 and PARP2 to assist olaparib in blocking PARP mediated repair of DNA SSBs. Meanwhile, BKM120 inhibited the expression of BRAC1/2 and Rad51/52 to block HR mediated repair through the PI3K/Akt/NFκB/c-Myc signaling pathway and PI3K/Akt/ FOXM1/Exo1 signaling pathway. BKM120 induced HR deficiency expanded the application of olaparib to HR proficient TNBCs. Our findings proved that PI3K inhibition impaired the repair of both DNA SSBs and DNA DSBs. FOXM1 and Exo1 are novel therapeutic targets that serves important roles in DNA damage response.

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“…N-acetyl-L-cysteine, L-ascorbic acid, and selenite (SeO 3 2− ) prevented AsO 2 − -induced apoptosis, oxidative stress, a cell viability decrease, mitochondrial disfunction, cytochrome c release, and an ROS production increase in experiments with L02 hepatocytes, mouse oligodendrocyte precursor cells, human myeloid leukemia U937 cells, and acute promyelocytic leukemia NB4 cells [279,[299][300][301]. The effect of SeO 3 2− can be caused by the inhibition of AsO 2 − transport in NB4 cells [301]. Pterostilbene or tert-butylhydroquinone activating the Nrf2 pathway alleviated similar AsO 2 − -induced effects in human HaCaT keratinocytes, mouse epidermal JB6 cells, and human epithelial HaCaT cells [302,303].…”

Section: Al(iii) Ga(iii) and In(iiimentioning

confidence: 99%

Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria

Korotkov

2023

IJMS

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This review analyzes the causes and consequences of apoptosis resulting from oxidative stress that occurs in mitochondria and cells exposed to the toxic effects of different-valence heavy metals (Ag+, Tl+, Hg2+, Cd2+, Pb2+, Al3+, Ga3+, In3+, As3+, Sb3+, Cr6+, and U6+). The problems of the relationship between the integration of these toxic metals into molecular mechanisms with the subsequent development of pathophysiological processes and the appearance of diseases caused by the accumulation of these metals in the body are also addressed in this review. Such apoptosis is characterized by a reduction in cell viability, the activation of caspase-3 and caspase-9, the expression of pro-apoptotic genes (Bax and Bcl-2), and the activation of protein kinases (ERK, JNK, p53, and p38) by mitogens. Moreover, the oxidative stress manifests as the mitochondrial permeability transition pore (MPTP) opening, mitochondrial swelling, an increase in the production of reactive oxygen species (ROS) and H2O2, lipid peroxidation, cytochrome c release, a decline in the inner mitochondrial membrane potential (ΔΨmito), a decrease in ATP synthesis, and reduced glutathione and oxygen consumption as well as cytoplasm and matrix calcium overload due to Ca2+ release from the endoplasmic reticulum (ER). The apoptosis and respiratory dysfunction induced by these metals are discussed regarding their interaction with cellular and mitochondrial thiol groups and Fe2+ metabolism disturbance. Similarities and differences in the toxic effects of Tl+ from those of other heavy metals under review are discussed. Similarities may be due to the increase in the cytoplasmic calcium concentration induced by Tl+ and these metals. One difference discussed is the failure to decrease Tl+ toxicity through metallothionein-dependent mechanisms. Another difference could be the decrease in reduced glutathione in the matrix due to the reversible oxidation of Tl+ to Tl3+ near the centers of ROS generation in the respiratory chain. The latter may explain why thallium toxicity to humans turned out to be higher than the toxicity of mercury, lead, cadmium, copper, and zinc.

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Dose-dependent effects of selenite (Se4+) on arsenite (As3+)-induced apoptosis and differentiation in acute promyelocytic leukemia cells

Cited by 21 publications

References 39 publications

Selenite promotes all-trans retinoic acid-induced maturation of acute promyelocytic leukemia cells

Selenite promotes all-trans retinoic acid-induced maturation of acute promyelocytic leukemia cells

BKM120 sensitizes BRCA-proficient triple negative breast cancer cells to olaparib through regulating FOXM1 and Exo1 expression

Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria

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