Heath T D, Brown C S, Stern W H
School of Pharmacy, University of Wisconsin Madison 53706.
Invest Ophthalmol Vis Sci. 1990 Jul;31(7):1245-51.
Fluoroorotate, tunicamycin, and actinomycin D exhibit optimal effects on cell contractility if cells are exposed to the drug for 72 hr, followed by 24 hr of exposure during the contractility assay. Under these conditions, fluoroorotate and tunicamycin inhibit contractility at concentrations very similar to those required to inhibit proliferation, and at higher concentrations affect cell viability. In contrast, the concentrations at which actinomycin D inhibits cell contractility and viability are very similar, and the concentration at which it inhibits cell proliferation is much lower. These results suggest that fluoroorotate and tunicamycin inhibit cell contractility by inhibiting membrane protein glycosylation. Actinomycin D, which inhibits RNA synthesis, appears to block cell contractility only by blocking cell viability, and its most potent effect inhibits only cell proliferation. Daunomycin exhibits very similar effects on cell contractility if cells are exposed to drug for 48 or 72 hr prior to the assessment of contractility, and its effects are not appreciably increased by the further inclusion of the drug for 24 hr during the contractility assay. Daunomycin also has appreciable effects on contractility if cells are exposed to the drug only for the 24 hr of the contractility assay. Similar to actinomycin D, daunomycin inhibits cell contractility and viability at similar concentrations, and inhibits cell proliferation at much lower concentrations. Moreover, daunomycin can appreciably inhibit cell viability in 24 hr of exposure. Therefore, daunomycin appears only to block cell contractility by blocking cell viability, and its most potent effect inhibits only cell proliferation.
如果在收缩性测定前，细胞暴露于氟乳清酸、衣霉素和放线菌素D 72小时，随后在收缩性测定期间再暴露24小时，那么这三种药物对细胞收缩性会呈现出最佳效果。在这些条件下，氟乳清酸和衣霉素抑制收缩性的浓度与抑制增殖所需的浓度非常相似，且在更高浓度下会影响细胞活力。相比之下，放线菌素D抑制细胞收缩性和活力的浓度非常相似，而其抑制细胞增殖的浓度则低得多。这些结果表明，氟乳清酸和衣霉素通过抑制膜蛋白糖基化来抑制细胞收缩性。抑制RNA合成的放线菌素D似乎仅通过阻断细胞活力来阻断细胞收缩性，其最显著的作用仅抑制细胞增殖。如果在评估收缩性之前，细胞暴露于柔红霉素48或72小时，那么柔红霉素对细胞收缩性会呈现出非常相似的效果，且在收缩性测定期间再加入该药物24小时，其效果不会明显增强。如果细胞仅在收缩性测定的24小时内暴露于柔红霉素，那么它对收缩性也有显著影响。与放线菌素D相似，柔红霉素在相似浓度下抑制细胞收缩性和活力，而在低得多的浓度下抑制细胞增殖。此外，柔红霉素在暴露24小时后就能显著抑制细胞活力。因此，柔红霉素似乎也仅通过阻断细胞活力来阻断细胞收缩性，其最显著的作用仅抑制细胞增殖。
