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Effects of retinoic acid metabolites on proliferation and differentiation of the clonal rhabdomyosarcoma cell line BA‐HAN‐1C
Author(s) -
Ramp Uwe,
Gerharz Claus Dieter,
Eifler Edith,
Biesalski Hans Konrad,
Gabbert Helmut Erich
Publication year - 1994
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1016/0248-4900(94)90052-3
Subject(s) - retinoic acid , biology , cell culture , cellular differentiation , cell growth , microbiology and biotechnology , biochemistry , genetics , gene
Summary— The clonal rat rhabdomyosarcoma cell line BA‐HAN‐IC is composed of proliferating mononuclear cells, some of which spontaneously fuse to terminally differentiated myotube‐like giant cells. This cell line has been shown to be susceptible to differentiation induction with all‐ trans retinoic acid (RA). Since it is still unknown whether exclusively all‐ trans RA itself or also its metabolites can act as inductive compounds in our cell line, we exposed BA‐HAN‐1C cells to the metabolites 4‐hydroxy RA, 4‐oxo RA and 5,6epoxy RA. Exposure to these RA metabolites resulted in a significant inhibition of proliferation (P < 0.001) and induction of cellular differentiation, as evidenced by a significant increase in the number of myotube‐like giant cells (P < 0.05) and a significant increase in creatine kinase activity (P < 0.05). However, differences in the inductive potency of these RA metabolites became apparent. Furthermore, RA metabolites exhibited a significantly weaker (P < 0.05) inductive activity when compared to all‐ trans RA. Summarizing our results we could demonstrate that the endogenous metabolites 4‐hydroxy RA, 4‐oxo RA and 5,6‐epoxy RA are not merely deactivated cellular excretion products of all‐ trans RA, but potent inducers of differentiation and inhibitors of proliferation, possibly contributing to the complex physiological actions of retinoic acid.