Singh Ajay P, Singh Rakesh K, Kim Kyu Kwang, Satyan K S, Nussbaum Roger, Torres Monica, Brard Laurent, Vorsa Nicholi
Department of Plant Biology and Plant Pathology, Rutgers University, New Brunswick, NJ 08019, USA.
Phytother Res. 2009 Aug;23(8):1066-74. doi: 10.1002/ptr.2667.
Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A-type PACs with 1-4 linkages containing between 2-8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79-479 microg/mL) but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 microg/ml). SKOV-3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3 cells with PACs (106 microg/ml) resulted in a significant reduction of the paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV-3 cell cultures co-treated with PAC-1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells.
对蔓越莓中主要类黄酮类的多酚提取物进行了体外筛选，以检测其对实体瘤细胞系的细胞毒性，确定了两个主要由原花青素（PACs）组成的具有潜在抗癌活性的组分。对原花青素（PACs）组分进行基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF-MS）分析表明，存在具有1-4连接的A型PACs，其含有2-8个表儿茶素单元，最多1个表没食子儿茶素单元。PACs对铂耐药的人卵巢癌、神经母细胞瘤和前列腺癌细胞系表现出体外细胞毒性（IC50 = 79-479微克/毫升），但对肺成纤维细胞无细胞毒性（IC50 > 1000微克/毫升）。用PACs处理的SKOV-3卵巢癌细胞表现出典型的凋亡变化。PACs在SKOV-3细胞中与顺铂发挥协同作用。用PACs（106微克/毫升）预处理SKOV-3细胞导致顺铂IC50值显著降低。同样，在BrdU掺入试验中，将SKOV-3细胞与PACs和顺铂共同处理显示，在比单独使用更低的浓度下细胞增殖减少。在与PAC-1和顺铂共同处理的SKOV-3细胞培养物中，HPLC分析表明存在不同定量的各种PAC低聚物，如DP-8、-9、-11和-14，表明存在选择性结合或摄取。蔓越莓原花青素在铂耐药的SKOV-3卵巢癌细胞中表现出细胞系特异性细胞毒性，诱导凋亡标志物并增强顺铂的细胞毒性。
