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Suppression of growth of hepatocellular carcinoma by sodium butyrate in vitro and in vivo
Author(s) -
Yamamoto Hidenao,
Fujimoto Jiro,
Okamoto Eizo,
Furuyama Junichi,
Tamaoki Taiki,
HashimotoTamaoki Tomoko
Publication year - 1998
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/(sici)1097-0215(19980610)76:6<897::aid-ijc21>3.0.co;2-z
Subject(s) - in vitro , hepatocellular carcinoma , in vivo , sodium butyrate , apoptosis , dna fragmentation , cell culture , growth inhibition , plating efficiency , fragmentation (computing) , biology , cancer research , microbiology and biotechnology , butyrate , cell growth , chemistry , programmed cell death , biochemistry , ecology , genetics , fermentation
Treatment of HuH‐7 human hepatocellular carcinoma (HCC) cells with 1–10 mM sodium butyrate (SB) resulted in growth inhibition in a dose‐dependent manner. At 3 mM and higher concentrations, SB caused nuclear fragmentation and DNA ladder formation characteristic of apoptosis. In the treated cells, the expression of p21 (WAF1/CIP1) increased and that of α‐fetoprotein (AFP) decreased. These characteristic changes were also observed with 5 other human HCC cell lines with or without mutation of the p53 gene. The ability of these cells to form colonies in soft agar was suppressed by either pretreating the cells with SB prior to soft agar plating or incubating untreated cells in SB‐containing soft agar. Direct injection of SB into tumors developed from HuH‐7 cells in nude mice resulted in an increase in the p21 level, a decrease in the tumor size and an increase in the survival time of mice. When the inoculation of HuH‐7 cells into nude mice was immediately followed by subcutaneous injection of SB, development of tumors was either significantly delayed or completely suppressed. These results suggest that SB induces cellular differentiation and suppresses growth and tumorigenicity of HCC cells in vitro and in vivo by a mechanism independent of p53 but possibly dependent on p21. Int. J. Cancer 76:897–902, 1998.© 1998 Wiley‐Liss, Inc.