Abe-Dohmae S, Ito J, Kato T, Tanaka R
Departments of Biochemistry and Bioregulation Research, Nagoya City University Medical School, Mizuho-ku, Nagoya 467, Japan.
Neurochem Int. 1990;17(1):93-100. doi: 10.1016/0197-0186(90)90072-2.
Synthesized sialosyl cholesterol (?-sialosyl cholesterol) induced growth inhibition of rat astrocytoma cells (GA-1) or schwannoma cells (354-A) which was detected as a decline of cell growth curves and a suppression of DNA syntheses. The incubation time to initiate growth inhibition of GA-1 was as short as 10 min and that to complete the action was 2 h after the initiation of drug-stimulation, indicating an immediate incorporation of sialosyl cholesterol into glioma cells. The morphological alteration of 354-A, but not GA-1, from an epithelioid cell shape to a spindle-like shape was also detected by the stimulation and ascertained by fluorescence visualization of cytoskeletons: the reorganization of actin filaments distributing as a plasmalemmal undercoat to form stress actin fibers and no detectable change in distribution of tubulins. The results provide a possibility that sialosyl cholesterol incorporated into the plasma membrane may cause growth inhibition of both glioma cells and morphological differentiation of schwannoma cells mostly through alterations of membrane characteristics and/or cytoskeletal anchorage, and also suggest the therapeutic potential of sialosyl cholesterol for brain tumors.
合成唾液酸胆固醇(α-唾液酸胆固醇)可诱导大鼠星形细胞瘤细胞(GA-1)或雪旺氏细胞瘤细胞(354-A)生长抑制,这可通过细胞生长曲线下降和DNA合成受抑制检测到。启动GA-1生长抑制的孵育时间短至10分钟,完成作用的时间是药物刺激开始后2小时,这表明唾液酸胆固醇可立即进入胶质瘤细胞。通过刺激还检测到354-A(而非GA-1)从上皮样细胞形态转变为纺锤样形态,并通过细胞骨架的荧光可视化得以确定:肌动蛋白丝作为质膜下涂层分布重新组织形成应激肌动蛋白纤维,微管蛋白分布无明显变化。这些结果表明,进入质膜的唾液酸胆固醇可能主要通过改变膜特性和/或细胞骨架锚定导致胶质瘤细胞生长抑制和雪旺氏细胞瘤细胞形态分化,也提示了唾液酸胆固醇对脑肿瘤的治疗潜力。