COMPARISON OF GROWTH STIMULATION OF HELA CELLS, HL-60 CELLS, AND MOUSE FIBROBLASTS BY COENZYME Q(10)

摘要

The addition of coenzyme Q(10) to culture media stimulates the serum-free growth of HeLa, HL-60 cells, and mouse fibroblasts (Balb/3T3). With HeLa cells, the stimulation by coenzyme Q(10) is additive to the stimulation by ferricyanide, an impermeable electron acceptor for the transplasma membrane electron transport. This combined response to coenzyme Q(10) and ferricyanide is enhanced with insulin. alpha-Tocopherylquinone can also stimulate the growth of HeLa cells, but vitamin K-1 is inactive. Specificity of quinone effects is indicated. Serum-free growth of Balb/3T3 and SV 40 transformed Balb/3T3 (SV/T2) cells is also stimulated by coenzyme Q(10) with stimulation similar to HeLa cells. However, Balb/3T3 cells are not stimulated by ferricyanide, which does not increase the response to coenzyme Q(10). The transformed cells (SV/T2) respond better to ferricyanide alone, but the effects of coenzyme Q(10) and ferricyanide are not additive. Serum-free growth of HL-60 cells is stimulated dramatically by coenzyme Q(10). The extent of growth stimulation on HL-60 cells is almost six-fold that of HeLa or Balb/3T3 cells. The stimulation of NADH-ferricyanide reductase (a transmembrane redox enzyme) by coenzyme Q(10) with HL-60 cells is similar to their growth pattern in response to coenzyme Q(10). Unlike HL-60, HeLa and Balb/3T3 cells show little stimulation of ferricyanide reduction by coenzyme Q(10). The stimulatory effect on both ferricyanide reduction and cell growth by the short side-chain coenzyme Q(2) is much less than that of the long side-chain coenzyme Q(10). Ferricyanide reduction by HeLa cells is inhibited by coenzyme Q analogs such as 2,3-dimethoxy-5-chloro-6-naphthyl-mercapto-coenzyme Q and 2-methoxy-3-ethoxyl-5-methyl-6-hexadecyl-mercapto-coenzyme Q. However, these inhibitions are reversed by coenzyme Q(10). The growth inhibition of HL-60 cells by other coenzyme Q analogs, such as capsiacin can also be reversed by coenzyme Q(10). These data indicate that plasma membrane-based NADH oxidation or modification of the membrane quinone redox balance may be a basis for the growth stimulation. [References: 34]