Effects of retinoic acid metabolites on proliferation and differentiation of the clonal rhabdomyosarcoma cell line BA-HAN-1C
Abstract
The clonal rat rhabdomyosarcoma cell line BA-HAN-1C 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 5,6-epoxy 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.
See also:
- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives);
- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;