Comparison of growth stimulation of HeLa cells, HL-60 cells, and mouse fibroblasts by coenzyme Q10

Abstract

The addition of coenzyme Q10 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 Q10 is additive to the stimulation by ferricyanide, an impermeable electron acceptor for the transplasma membrane electron transport. This combined response to coenzyme Q10 and ferricyanide is enhanced with insulin. α-Tocopherylquinone can also stimulate the growth of HeLa cells, but vitamin K1 is inactive. Specificity of quinone effects is indicated. Serum-free growth of Balb/3T3 and SV 40 transformed BaIb/3T3 (SV/T2) cells is also stimulated by coenzyme Qio with stimulation similar to HeLa cells. However, Balb/3T3 cells are not stimulated by ferricyanide, which does not increase the response to coenzyme Q10. The transformed cells (SV/T2) respond better to ferricyanide alone, but the effects of coenzyme Qio and ferricyanide are not additive. Serum-free growth of HL-60 cells is stimulated dramatically by coenzyme Q10. 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 Q10 with HL-60 cells is similar to their growth pattern in response to coenzyme Q10. Unlike HL-60, HeLa and Balb/3T3 cells show little stimulation of ferricyanide reduction by coenzyme Q10. The stimulatory effect on both ferricyanide reduction and cell growth by the short side-chain coenzyme Q2 is much less than that of the long side-chain coenzyme Q10. 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 Q10. The growth inhibition of HL-60 cells by other coenzyme Q analogs, such as capsiacin can also be reversed by coenzyme Q10. 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.