Methylcobalamin Decreases mRNA Levels of Androgen-Induced Growth Factor in Androgen-Dependent Shionogi Carcinoma 115 Cells

Abstract

Methylcobalamin (MeCbl) is an important enzyme cofactor required for methionine synthase activity. It also inhibits, in a dose-dependent manner, the proliferation of an androgen-dependent cell line, SC-3, derived from an androgen-dependent mouse mammary tumor (Shionogi carcinoma 115). In SC-3 cells, androgen induces the production of androgen-induced growth factor (AIGF), an autocrine growth factor increasing the proliferation of SC-3 cells. MeCbl treatment suppressed the androgen-induced, AIGF-mediated growth of SC-3 cells, as well as the androgen-induced increase of AIGF mRNA. In SC-3 cells, androgen receptors linked with androgen form complexes that tightly bind DNA and act as transcription factors in the nucleus to regulate the expression of specific genes such as AIGF. The number and dissociation constants of androgen receptors in control and MeCbl-treated SC-3 cells were the same. Similarly, the extent of binding of normal androgen receptors in nuclei from control and MeCbl-treated cells was virtually identical. The androgen receptors from control and MeCbl-treated cells showed similar capacities for conversion to a form that tightly binds to DNA on heat activation. These results suggest that the reduction of AIGF mRNA, subsequent to the nuclear binding of androgen receptors, may be a partial cause of the growth-inhibitory activity of MeCbl in SC-3 cells.

Propionylcarnitine and methionine concentrations in newborns with hypospadias

“…Androgen and androgen receptors have been thought to play a crucial role in male external genital development [2]. Interestingly, in a dose-dependant manner, cobalamin influences the proliferation of androgen–dependent cell lines [16]. Susceptibility to vitamin B 12 status might depend not only on the low level of cobalamin, indexed as increased propionylcarnitine, itself, but also on individual sensitivity modulated by genetic background, including gene polymorphisms and epigenetic modifications.…”