Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 171

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Arsenic trioxide–induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL

Liu, Qun, Hilsenbeck, Susan, Gazitt, Yair·2003·Blood
DOI 10.1182/blood-2002-10-3231
Open this paper in CoChat — free account

Abstract

Arsenic trioxide (ATO) has been shown to induce differentiation and apoptosis in acute promyelocytic leukemia (APL) cells concomitant with down-regulation of the PML-RARα fusion protein, a product of the t(15:17) translocation characteristic of APL leukemic cells. However, ATO is also a potent inducer of apoptosis in a number of other cancer cells lacking the t(15:17) translocation. The exact mechanism of ATO-induced apoptosis in these cells is not yet clear. We tested the effect of ATO on 7 myeloma cell lines with varying p53 status and report that in cells with mutated p53, ATO induced rapid and extensive (more than 90%) apoptosis in a time- and dose-dependent manner concomitant with arrest of cells in G2/M phase of the cell cycle. Myeloma cells with wild-type (wt) p53 were relatively resistant to ATO with maximal apoptosis of about 40% concomitant with partial arrest of cells in G1 and up-regulation of p21. The use of caspase blocking peptides, fluorescence-tagged caspase-specific substrate peptides, and Western immunoblotting confirmed the involvement of primarily caspase-8 and -3 in ATO-induced apoptosis in myeloma cells with mutated p53 and primarily caspase-9 and -3 in cells expressing wt p53. We also observed up-regulation by ATO of R1 and R2 APO2/TRAIL (tumor necrosis factor–related apoptosis-inducing ligand) receptors. Most important, however, we observed a synergy between ATO and APO2/TRAIL in the induction of apoptosis in the partially resistant myeloma cell lines and in myeloma cells freshly isolated from myeloma patients. Our results justify the use of the combination of these 2 drugs in clinical setting in myeloma patients.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1182/blood-2002-10-3231

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 2 references

Research works printed but not linked: 54

  1. Gregory, 1992, Combination chemotherapy versus melphalan and prednisone in the treatment of multiple myeloma: an overview of published trials., J Clin Oncol., 10, 336, 10.1200/JCO.1992.10.2.334 · DOI · Paper page
  2. Alexanian, 1992, Primary dexamethasone treatment for multiple myeloma., Blood., 80, 887, 10.1182/blood.V80.4.887.887 · DOI · Paper page
  3. Attal, 1996, A prospective randomized trial of autologous transplantation and chemotherapy in multiple myeloma., N Engl J Med., 335, 91, 10.1056/NEJM199607113350204 · DOI · Paper page
  4. Soignet, 1998, Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide., N Engl J Med., 339, 1341, 10.1056/NEJM199811053391901 · DOI · Paper page
  5. Cai, 2000, Arsenic trioxide-induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia., Leukemia., 14, 262, 10.1038/sj.leu.2401650 · DOI · Paper page
  6. Hu, 1999, Long-term survival and prognostic study in acute promyelocytic leukemia treated with ATRA, chemotherapy, and As2O3: an experience of 120 patients., Int J Hematol., 70, 248
  7. Perkins, 2000, Arsenic induces apoptosis of multidrug-resistant human myeloid leukemia cells that express Bcr-Abl or overexpress MDR, MRP, Bcl-2, or Bcl-xL., Blood., 95, 1014, 10.1182/blood.V95.3.1014.003k04_1014_1022 · DOI · Paper page
  8. Zhang, 1999, Induction of apoptosis and inhibition of human gastric cancer MGC-803 cell growth by arsenic trioxide., Eur J Cancer., 35, 1258, 10.1016/S0959-8049(99)00106-9 · DOI
  9. Ora, 2000, Arsenic trioxide inhibits neuroblastoma growth in vivo and promotes apoptotic cell death in vitro., Biochem Biophys Res Commun., 277, 179, 10.1006/bbrc.2000.3651 · DOI
  10. Akao, 1999, Arsenic trioxide induces apoptosis in neuroblastoma cell lines through the activation of caspase 3 in vitro., FEBS Lett., 455, 59, 10.1016/S0014-5793(99)00841-8 · DOI · Paper page
  11. Park, 2000, Arsenic trioxide-mediated growth inhibition in MC/CAR myeloma cells via cell cycle arrest and induction of cyclin-dependent kinase inhibitor, p21, and apoptosis., Cancer Res., 60, 3065
  12. Kinjo, 2000, Arsenic trioxide (As2O3)-induced apoptosis and differentiation in retinoic acid-resistant acute promyelocytic leukemia model in hGM-CSF-producing transgenic SCID mice., Leukemia., 14, 431, 10.1038/sj.leu.2401646 · DOI
  13. Rego, 1017, Retinoic acid (RA) and As2O3 treatment in transgenic models of acute promyelocytic leukemia (APL) unravel the distinct nature of the leukemogenic process induced by the PML-RARα and PLZF-RARα oncoproteins., Proc Natl Acad Sci U S A., 200, 97
  14. Shen, 2000, Multiple mechanisms are involved in differentiation induced by arsenic trioxide in acute promyelocytic leukemia [abstract]., Blood., 96, 310a
  15. Shen, 2000, The alteration of mitochondria is an early event of arsenic trioxide induced apoptosis in esophageal carcinoma cells., Int J Mol Med., 5, 155
  16. Warrell, 1999, Arsenicals and inhibitors of histone deacetylase as anticancer therapy., Haematologica., 84, 75
  17. Park, 2001, Arsenic trioxide induces G2/M growth arrest and apoptosis after caspase-3 activation and bcl-2 phosphorylation in promonocytic U937 cells., Biochem Biophys Res Commun., 6, 726, 10.1006/bbrc.2001.5416 · DOI
  18. Jiang, 2001, Arsenic trioxide induces apoptosis in human gastric cancer cells through up-regulation of p53 and activation of caspase-3., Int J Cancer., 93, 916, 10.1002/ijc.1442 · doi:10.1002/ijc.1442
  19. Seol, 2001, Potential role of caspase-3 and -9 in arsenic trioxide-mediated apoptosis in PCI-1 head and neck cancer cells., Int J Oncol., 18, 249
  20. Kitamura, 2000, Involvement of CD95-independent caspase 8 activation in arsenic trioxide-induced apoptosis., Leukemia., 14, 1743, 10.1038/sj.leu.2401900 · DOI
  21. Pitti, 1996, Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family., J Biol Chem., 271, 12687, 10.1074/jbc.271.22.12687 · DOI · Paper page
  22. Marsters, 1996, Apo-3, a new member of the tumor necrosis factor receptor family, contains a death domain and activates apoptosis and NF-κ B., Curr Biol., 6, 1669, 10.1016/S0960-9822(02)70791-4 · DOI
  23. Griffith, 1998, Intracellular regulation of APO2/TRAIL-induced apoptosis in human melanoma., J Immunol., 161, 2833, 10.4049/jimmunol.161.6.2833 · DOI · Paper page
  24. Pan, 1997, An antagonistic decoy receptor and a death domain containing receptor for APO2/TRAIL., Science., 277, 815, 10.1126/science.277.5327.815 · DOI · Paper page
  25. Sheikh, 1999, The antiapoptotic decoy receptor TRID/APO2/TRAIL-R3 is a p53 regulated DNA damage inducible gene that is overexpressed in primary tumors of the gastrointestinal tract., Oncogene., 18, 4153, 10.1038/sj.onc.1202763 · DOI
  26. Sheridan, 1997, Control of APO2/TRAIL-induced apoptosis by a family of signaling and decoy receptors., Science., 277, 818, 10.1126/science.277.5327.818 · DOI · Paper page
  27. Kim, 2000, Molecular determinants of response to APO2/TRAIL in killing of normal and cancer cells., Clin Cancer Res., 6, 335
  28. Sprick, 2000, FADD/MORT1 and caspase-8 are recruited to APO2/TRAIL receptors 1 and 2 and are essential for apoptosis mediated by APO2/TRAIL receptor 2., Immunity., 12, 599, 10.1016/S1074-7613(00)80211-3 · DOI · Paper page
  29. Kischkel, 2000, APO2/TRAIL dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5., Immunity., 12, 611, 10.1016/S1074-7613(00)80212-5 · DOI · Paper page
  30. Gazitt, 1999, Apoptosis induced by APO2/TRAIL and TNFα in human multiple myeloma cells is not blocked by bcl-2., Cytokine., 11, 1010, 10.1006/cyto.1999.0536 · DOI
  31. Gazitt, 1999, APO2/TRAIL is a potent inducer of apoptosis in myeloma cells derived from multiple myeloma patients and is not cytotoxic to hematopoietic stem cells., Leukemia., 13, 1817, 10.1038/sj.leu.2401501 · DOI
  32. Liu, 2000, Adenovirus-mediated delivery of p53 results in a substantial apoptosis to myeloma cells and is not cytotoxic to flow-sorted CD34+ hematopoietic progenitor cells and normal lymphocytes., Exp Hematol., 28, 1354, 10.1016/S0301-472X(00)00556-7 · doi:10.1016/s0301-472x(00)00556-7
  33. Kim, 2001, Enhanced APO2/TRAIL sensitivity by p53 overexpression in human cancer but not normal cells., Int J Oncol., 18, 241
  34. Liu, 2001, Additive effect of Apo2L/TRAIL and Adeno-p53 in the induction of apoptosis in myeloma cell lines., Exp Hematol., 29, 962, 10.1016/S0301-472X(01)00677-4 · DOI
  35. Wu, 1997, KILLER/DR5 is a DNA damage-inducible, p53 regulated death receptor gene., Nat Genet., 17, 141, 10.1038/ng1097-141 · DOI · Paper page
  36. Nagane, 2000, Increased death receptor 5 expression by chemotherapeutic agents in human gliomas causes synergistic cytotoxicity with tumor necrosis factor related apoptosis inducing ligand in vitro and in vivo., Cancer Res., 60, 847
  37. Gliniak, 1999, Tumor necrosis factor-related apoptosis inducing ligand's antitumor activity in vivo is enhanced by the chemotherapeutic agent CPT-11., Cancer Res., 59, 6153
  38. Chinnaiyan, 2000, Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy., Proc Natl Acad Sci U S A., 97, 1754, 10.1073/pnas.030545097 · DOI · Paper page
  39. Ashkenazi, 1999, Safety and antitumor activity of recombinant soluble Apo2 ligand., J Clin Invest., 104, 155, 10.1172/JCI6926 · DOI · Paper page
  40. Gazitt, 2001, The mechanism of arsenic trioxide (ATO, Trisenox)-induced apoptosis: independence of Bcl-2; involvement of G2/M cell cycle arrest and upregulation of surface APO2/TRAIL-receptors [abstract]., Blood., 98, 159a
  41. Gazitt, 1998, Bcl-2 overexpression is associated with resistance to paclitaxel but not gemcitabine in multiple myeloma cell lines., Int J Oncol., 13, 839
  42. Mazars, 1992, Mutation of p53 gene in human myeloma cell lines., Oncogene., 7, 1015
  43. Tian, 1996, Bcl-2 plays a critical role in growth and in spontaneous or induced apoptosis in myeloma cell lines: a study with inducible bcl-2 transfection constructs., Int J Oncol., 9, 165
  44. Tian, 1996, The role of P53, bcl-2 and bax in dexamethasone induced apoptosis in myeloma cell lines., Int J Oncol., 8, 719
  45. Laska, 1994, Simple designs and model-free tests for synegy., Biometrics., 50, 834, 10.2307/2532796 · DOI
  46. Woods, 2001, Regulation of p53 function., Exp Cell Res., 264, 56, 10.1006/excr.2000.5141 · DOI · Paper page
  47. Bargonetti, 2002, Multiple roles of the tumor suppressor p53., Curr Opin Oncol., 14, 86, 10.1097/00001622-200201000-00015 · DOI · Paper page
  48. Oda, 2000, p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53., Cell., 102, 849, 10.1016/S0092-8674(00)00073-8 · DOI · Paper page
  49. Taylor, 2001, Regulation of the G2/M transition by p53., Oncogene., 20, 1803, 10.1038/sj.onc.1204252 · DOI · Paper page
  50. Lacour, 2001, Anticancer agents sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis., Cancer Res., 61, 1645
  51. Mitsiades, 2002, Intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human multiple myeloma cells., Blood., 99, 2162, 10.1182/blood.V99.6.2162 · DOI
  52. Adams, 1998, The bcl-2 protein family: arbiters of cell survival., Science., 281, 1322, 10.1126/science.281.5381.1322 · DOI · Paper page
  53. Roth, 2002, Apoptosis and cancer: when BAX is TRAILing away., Nat Med., 8, 216, 10.1038/nm0302-216 · DOI
  54. Sun, 2000, Augmentation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by the synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) through up-regulation of TRAIL receptors in human lung cancer cells., Cancer Res., 60, 7149

Cited by

See all 171

Metadata

Authors
Liu, Q., Hilsenbeck, S., & Gazitt, Y.
Affiliations
From the University of Texas Health Science Center, San Antonio; and Breast Center, Baylor College of Medicine, Houston, TX.
Venue
Blood
Publisher
American Society of Hematology
Published
2003-05-15
Volume
101
Issue
10
Pages
4078-4087
ISSN
  • 1528-0020
  • 0006-4971
DOI
10.1182/blood-2002-10-3231
Cited by
171
References
2
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Arsenic trioxide–induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL. https://app.cochat.ai/papers/10.1182/blood-2002-10-3231
The paper
Liu, Q., Hilsenbeck, S., & Gazitt, Y. (2003). Arsenic trioxide–induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL. Blood. https://doi.org/10.1182/blood-2002-10-3231

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.