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Growth and intestinal differentiation are independently regulated in HT29 colon cancer cells
Author(s) -
Schroy Paul C.,
Rustgi Anil K.,
Ikonomu Ekaterini,
Liu Xiu P.,
Polito Joseph,
Andry Chris,
O'Keane J. Connor
Publication year - 1994
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041610114
Subject(s) - sodium butyrate , cellular differentiation , alkaline phosphatase , cell growth , differentiation therapy , biology , cell , cancer research , microbiology and biotechnology , chemistry , cell culture , biochemistry , enzyme , genetics , acute promyelocytic leukemia , retinoic acid , gene
The polar‐planar compound hexamethylene bisacetamide (HMBA) can inhibit HT29 colon carcinoma cell growth and induce a more benign phenotype, as defined by decreased anchorage‐independent clonogenicity, loss of a cell surface malignancy marker, and decreased in vivo tumorigenicity. The principle aim of this study was to determine whether HMBA's effects on HT29 cell growth and biologic behavior correlate with effects on intestinal differentiation. Parallel studies were performed with sodium butyrate (NaBT), a potent inducer of intestinal differentiation HT29 cell growth, proliferation, and markers of intestinal differentiation were assayed after short‐ and long‐term treatment with HMBA, NaBT, or the combination. Both 5 mM HMBA and 5 mM NaBT were potent inhibitors of monolayer growth; in combination their effects were nearly additive. Inhibition of DNA synthesis was detectable within 6 h of treatment and was preceded by down‐regulation of c‐ myc expression. Soft agar clonogenicity was also decreased by 90%, > 99%, and > 99% by HMBA, NaBT, and the combination, respectively. Despite these parallel effects on growth and in vitro markers of a benign phenotype, effects on intestinal differentiation were discordant. NaBT induced significant increases in membrane‐associated alkaline phosphatase activity, cytosolic mucin content, PAS + /diastase‐resistant cells, and ultrastructural evidence of intestinal cell differentiation. HMBA not only failed to induce markers of intestinal differentiation, but attenuated NaBT's effects when used in combination. These data suggest that growth and intestinal differentiation may be independently regulated in HT29 cells. They also suggest that expression of intestinal markers of differentiation is not a prerequisite for the acquisition of a more benign phenotype. © 1994 Wiley‐Liss, Inc.