Histone deacetylase inhibitors and retinoic acids inhibit growth of human neuroblastoma in vitro Journal Article

  


Authors: Coffey, D. C.; Kutko, M. C.; Glick, R. D.; Swendeman, S. L.; Butler, L.; Rifkind, R.; Marks, P. A.; Richon, V. M.; LaQuaglia, M. P.
Article Title: Histone deacetylase inhibitors and retinoic acids inhibit growth of human neuroblastoma in vitro
Abstract: Background. Neuroblastoma is a common childhood cancer with a poor overall prognosis. Retinoic acids (RAs) have been studied as a potential therapy, showing promise in recurrent disease. The histone deacetylase inhibitor (HDACI) M-carboxycinnamic acid bishydroxamide (CBHA) is another potential therapy, which we recently described. Combinations of RAs and HDACIs currently under investigation display synergy in certain neoplasms. In this study, we evaluate the effect of combinations of RAs and HDACIs on human neuroblastoma cells. Procedure. Established cell lines were cultured in increasing concentrations of HDA-CIs, RAs, and combinations thereof. Following exposure, viable cell number was quantified by trypan blue dye exclusion on a hemacytometer. Cell cycle analysis was performed by propidium iodide staining and FACS. Results. All assayed HDACIs and RAs decreased viable cell number. Lower concentrations of each agent were effective when the two were combined. The primary reason for decreased cell number appears to be apoptosis following HDACI exposure and G1 arrest following RA exposure. Both effects are seen with cotreatment. Caspase inhibition abrogates the apoptotic response. Conclusions. CBHA causes apoptosis of human neuroblastoma in vitro, an effect that can add to the effects of RA. HDACIs and RAs inhibit neuroblastoma in significantly lower concentrations when used together than when used individually. Combination therapy may improve the ultimate efficacy while reducing the side effects of these agents in clinical use. (C) 2000 Wiley-Liss, Inc.
Keywords: controlled study; unclassified drug; human cell; drug efficacy; drug potentiation; conference paper; cell cycle; cell division; apoptosis; antineoplastic combined chemotherapy protocols; tumor cells, cultured; caspases; childhood cancer; drug mechanism; neuroblastoma; tumor cell line; histone deacetylase inhibitors; histone deacetylases; g1 phase; histone deacetylase; carboxycinnamic acid bishydroxamide; cinnamic acid derivative; cinnamates; tretinoin; retinoic acids; drug mixture; retinoic acid derivative; humans; prognosis; human; priority journal
Journal Title: Medical and Pediatric Oncology
Volume: 35
Issue: 6
ISSN: 0098-1532
Publisher: Wiley Liss  
Date Published: 2000-12-01
Start Page: 577
End Page: 581
Language: English
DOI: 10.1002/1096-911x(20001201)35:6<577::aid-mpo18>3.0.co;2-3
PUBMED: 11107121
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0033646839&partnerID=40&md5=89e00a28266952e0a755e6b51f1f7977
Notes: Export Date: 18 November 2015 -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Victoria M Richon
    91 Richon
  2. Steven L Swendeman
    15 Swendeman
  3. Michael P La Quaglia
    411 La Quaglia
  4. Lisa M Butler-van Den Heuvel
    8 Butler-van Den Heuvel
  5. Paul Marks
    186 Marks
  6. Richard Rifkind
    118 Rifkind
Related MSK Work