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Phenylacetate synergizes with retinoic acid in inducing the differentiation of human neuroblastoma cells
Author(s) -
Sidell Neil,
Wada Randal,
Han Guangyang,
Chang Bieshia,
Shack Sonsoles,
Moore Theodore,
Samid Divorit
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910600414
Subject(s) - phenylacetate , retinoic acid , neuroblastoma , cellular differentiation , cancer research , tretinoin , chemistry , biology , microbiology and biotechnology , endocrinology , biochemistry , cell culture , genetics , gene
Phenylacetate, a natural metabolite of phenylalanine which was originally described as a plant growth hormone, has recently gained attention as a possible differentiation inducer for a variety of human tumor cell types. This interest prompted us to assess the ability of sodium phenylacetate (NaPA) to promote the differentiation of human neuroblastoma cells, both alone and in combination with retinoic acid (RA), a known inducer of neuroblastoma differentiation and maturation. Using the LA‐N‐5 cell line, we have determined that NaPA can stimulate the differentiation of neuroblastoma cells, as evidenced by dose‐dependent inhibition of cell proliferation, neu‐rite outgrowth, increased acetylcholinesterase activity and reduction of N‐myc expression. Furthermore, NaPA and RA synergized in inducing differentiation, in that combination treatment resulted in cessation of cell growth along with morphologic and biochemical changes indicative of the loss of malignant properties. We have determined that NaPA can markedly enhance mRNA levels of the nuclear RA receptor‐β (RARβ) in LA‐N‐5 cells prior to morphologic or other pheno‐typic changes induced by this compound. This effect appeared to be distinct from the ability of NaPA to alter tumor cell lipid metabolism via inhibition of protein isoprenylation. Thus among its varied effects on LA‐N‐5 cells, NaPA appears to interact with the RA pathway at the nuclear level by up‐regulating RARβ expression.