Kuo C L, Chou C C, Yung B Y
Graduate Institute of Pharmacology, Yang Ming Medical College, Taiwan, ROC.
Cancer Lett. 1995 Jul 13;93(2):193-200. doi: 10.1016/0304-3835(95)03809-b.
Berberine, an alkaloid initially isolated from Chinese herbal medicine exhibited the ability to induce morphological changes and internucleosomal DNA fragmentation, characteristic of apoptosis in promyelocytic leukemia HL-60 cells. Cell cycle studies showed that only about 20% of the cells underwent apoptosis at the early time (6 h) of berberine (25 micrograms/ml) treatment; these appeared to be cells in S phase at the time of berberine treatment. At extended time (6-48 h), cells were cell cycle arrested, the number of cells of each phase, particularly the cells of S phase decreased and much more (> 50%) of the cells appeared with DNA content less than G1. Attempts were also made to isolate possible berberine-DNA complexes from cell cultures treated with berberine (25 micrograms/ml; 2-24 h). Shifts of absorption maxima of berberine in the direction of longer wavelengths were observed in the isolated berberine-DNA complexes. Palmatine, an analog of berberine, which was not able to induce apoptosis, also complexed with DNA in cells treated with palmatine (25 micrograms/ml; 2-24 h). Our results suggest that some important cellular processes other than the intracellular DNA-interacting action of berberine may be involved in the berberine-induced apoptosis in HL-60 cells.
小檗碱是一种最初从中药中分离出来的生物碱，它能够诱导早幼粒细胞白血病HL-60细胞发生形态变化和核小体间DNA断裂，这些是细胞凋亡的特征。细胞周期研究表明，在小檗碱（25微克/毫升）处理的早期（6小时），只有约20%的细胞发生凋亡；这些细胞在小檗碱处理时似乎处于S期。在延长时间（6 - 48小时）时，细胞出现细胞周期停滞，各期细胞数量，尤其是S期细胞数量减少，并且更多（>50%）的细胞出现DNA含量低于G1期的情况。研究人员还尝试从用小檗碱（25微克/毫升；2 - 24小时）处理的细胞培养物中分离可能的小檗碱 - DNA复合物。在分离出的小檗碱 - DNA复合物中观察到小檗碱的吸收峰向更长波长方向移动。巴马汀是小檗碱的类似物，它不能诱导细胞凋亡，但在用巴马汀（25微克/毫升；2 - 24小时）处理的细胞中也能与DNA结合。我们的结果表明，除了小檗碱与细胞内DNA相互作用的作用外，一些重要的细胞过程可能也参与了小檗碱诱导HL-60细胞凋亡的过程。
