Choi S U, Ryu S Y, Yoon S K, Jung N P, Park S H, Kim K H, Choi E J, Lee C O
Pharmaceutical Screening Center, Korea Research Institute of Chemical Technology, Yusong, Taejon, Korea.
Anticancer Res. 1999 Nov-Dec;19(6B):5229-33.
In this study, we investigated the cytotoxicities of flavone (F01), 3-hydroxyflavone (F02), 6- hydroxyflavone (F03), 7-hydroxyflavone (F04), 3,6-dihydroxyflavone (F05), 5,7-dihydroxyflavone (F06) and 5,6,7-trihydroxyflavone (F07) to human cancer cells including P- glycoprotein (Pgp)-expressing HCT15 cells and its multidrug resistant subline, HCT15/CL02 cells. We also examined the effects of those flavonoids on the cell cycle of these cancer cells. HCT15/CL02 cells did not reveal resistance to all the flavonoids tested in comparison with HCT15 cells. In cell cycle analysis, all the flavonoids tested, except F01 and F04, reduced the G0/G1 population of SF295 cells at growth inhibitory concentrations, and increased G2/M (F02, F03 and F06) or S (F05 and F07) populations. In addition, F02 and F03 decreased the G2/M and G0/G1 population, and increased the S and G2/M population in HCT15 cells, respectively. Meanwhile, in HCT15/CL02 cells, F02 and F03 decreased the G0/G1 populations and increased the S population. In conclusion, we deemed that the flavonoids tested had diverse cytotoxic mechanisms, and exerted their cell growth inhibitory or killing activity by distinctive ways in different cells.
在本研究中，我们调查了黄酮（F01）、3 - 羟基黄酮（F02）、6 - 羟基黄酮（F03）、7 - 羟基黄酮（F04）、3,6 - 二羟基黄酮（F05）、5,7 - 二羟基黄酮（F06）和5,6,7 - 三羟基黄酮（F07）对包括表达P - 糖蛋白（Pgp）的HCT15细胞及其多药耐药亚系HCT15/CL02细胞在内的人类癌细胞的细胞毒性。我们还研究了这些黄酮类化合物对这些癌细胞细胞周期的影响。与HCT15细胞相比，HCT15/CL02细胞对所有测试的黄酮类化合物均未表现出耐药性。在细胞周期分析中，除F01和F04外，所有测试的黄酮类化合物在生长抑制浓度下均降低了SF295细胞的G0/G1期细胞比例，并增加了G2/M期（F02、F03和F06）或S期（F05和F07）细胞比例。此外，F02和F03分别降低了HCT15细胞的G2/M期和G0/G1期细胞比例，并增加了S期和G2/M期细胞比例。同时，在HCT15/CL02细胞中，F02和F03降低了G0/G1期细胞比例并增加了S期细胞比例。总之，我们认为所测试的黄酮类化合物具有不同的细胞毒性机制，并在不同细胞中通过独特的方式发挥其细胞生长抑制或杀伤活性。
