Chowdhury Shahead Ali, Kishino Kaori, Satoh Rie, Hashimoto Ken, Kikuchi Hirotaka, Nishikawa Hirofumi, Shirataki Yoshiaki, Sakagami Hiroshi
Meikai Pharmaco-Medical Laboratory (MPL), Meikai University School of Dentistry, Sakado, Saitama, Japan.
Anticancer Res. 2005 May-Jun;25(3B):2055-63.
A total of eleven stilbenes [1-6] and flavonoids [7-11] were investigated for their tumor- specific cytotoxicity and apoptosis-inducing activity, using four human tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG and promyelocytic leukemia HL-60) and three normal human oral cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF). All of the compounds, especially sophorastilbene A [1], (+)-alpha-viniferin [2], piceatannol [5], quercetin [9] and isoliquiritigenin [10], showed higher cytotoxicity against the tumor cell lines than normal cells, yielding tumor-specific indices of 3.6, 4.7, >3.5, >3.3 and 4.0, respectively. Among the seven cell lines, HSC-2 and HL-60 cells were the most sensitive to the cytotoxic action of these compounds. Sophorastilbene A [1], piceatannol [5], quercetin [9] and isoliquiritigenin [10] induced internucleosomal DNA fragmentation and activation of caspases -3, -8 and -9 dose-dependently in HL-60 cells. (+)-alpha-Viniferin [2] showed similar activity, but only at higher concentrations. All the compounds failed to induce DNA fragmentation and activated caspases to much lesser extents in HSC-2 cells. Western blot analysis showed that sophorastilbene A [1], piceatannol [5] and quercetin [9] did not induce any consistent changes in the expression of pro-apoptotic proteins (Bax, Bad) and antiapoptotic protein (Bcl-2) in HL-60 and HSC-2 cells. An undetectable expression of Bcl-2 protein in control and drug-treated HSC-2 cells may explain the relatively higher sensitivity of this cell line to stilbenes and flavonoids.
研究了总共11种芪类化合物[1 - 6]和黄酮类化合物[7 - 11]对肿瘤的特异性细胞毒性和诱导凋亡活性，使用了四种人类肿瘤细胞系（鳞状细胞癌HSC - 2、HSC - 3、下颌下腺癌HSG和早幼粒细胞白血病HL - 60）以及三种正常人类口腔细胞（牙龈成纤维细胞HGF、牙髓细胞HPC、牙周膜成纤维细胞HPLF）。所有这些化合物，尤其是槐果芪A[1]、(+)-α-葡萄素[2]、白皮杉醇[5]、槲皮素[9]和异甘草素[10]，对肿瘤细胞系的细胞毒性高于正常细胞，其肿瘤特异性指数分别为3.6、4.7、>3.5、>3.3和4.0。在这七种细胞系中，HSC - 2和HL - 60细胞对这些化合物的细胞毒性作用最为敏感。槐果芪A[1]、白皮杉醇[5]、槲皮素[9]和异甘草素[10]在HL - 60细胞中剂量依赖性地诱导核小体间DNA片段化以及半胱天冬酶-3、-8和-9的激活。(+)-α-葡萄素[2]表现出类似的活性，但仅在较高浓度下。所有化合物在HSC - 2细胞中诱导DNA片段化和激活半胱天冬酶的程度要小得多。蛋白质印迹分析表明，槐果芪A[1]、白皮杉醇[5]和槲皮素[9]在HL - 60和HSC - 2细胞中未诱导促凋亡蛋白（Bax、Bad）和抗凋亡蛋白（Bcl - 2）表达的任何一致变化。在对照和药物处理的HSC - 2细胞中未检测到Bcl - 2蛋白的表达，这可能解释了该细胞系对芪类化合物和黄酮类化合物相对较高的敏感性。
