Sudan Sudhanshu, Rupasinghe H P Vasantha
a Department of Environmental Sciences, Faculty of Agriculture , Dalhousie University , Truro , Nova Scotia , Canada.
Nutr Cancer. 2014;66(7):1237-46. doi: 10.1080/01635581.2014.951733. Epub 2014 Sep 25.
Apples are a major source of dietary phytochemicals such as flavonoids in the Western diet. Here we report anticancer properties and possible mechanism of action of apple flavonoid-enriched fraction (AF4) isolated from the peels of Northern Spy apples in human hepatocellular carcinoma cells, HepG2. Treatment with AF4 induced cell growth inhibition in HepG2 cells in time- and dose-dependent manner. Concentration of 50 μg/ml (50 μg total monomeric polyphenols/ml) AF4 was sufficient to induce a significant reduction in cell viability within 6 h of treatment (92%, P < 0.05) but had very low toxicity (minimum 4% to maximum 16%) on primary liver and lung cells, which was significantly lower than currently prescribed chemotherapy drug Sorafenib (minimum 29% to maximum 49%, P < 0.05). AF4 induced apoptosis in HepG2 cells within 6 h of treatment via activation of caspase-3. Cell cycle analysis via flow-cytometer showed that AF4 induced G2/M phase arrest. Further, results showed that AF4 acts as a strong DNA topoisomerase II catalytic inhibitor, which may be a plausible reason to drive the cells to apoptosis. Overall, our data suggests that AF4 possesses a significantly stronger antiproliferative and specific action than Sorafenib in vitro and is a potential natural chemotherapy agent for treatment of liver cancer.
在西方饮食中，苹果是膳食植物化学物质（如类黄酮）的主要来源。在此，我们报告了从北方间谍苹果皮中分离出的富含苹果类黄酮的组分（AF4）在人肝癌细胞HepG2中的抗癌特性及可能的作用机制。用AF4处理以时间和剂量依赖的方式诱导HepG2细胞的生长抑制。50μg/ml（50μg总单体多酚/ml）的AF4浓度足以在处理6小时内诱导细胞活力显著降低（92%，P<0.05），但对原代肝细胞和肺细胞的毒性非常低（最低4%至最高16%），这显著低于目前处方的化疗药物索拉非尼（最低29%至最高49%，P<0.05）。AF4在处理6小时内通过激活caspase-3诱导HepG2细胞凋亡。通过流式细胞仪进行的细胞周期分析表明，AF4诱导G2/M期阻滞。此外，结果表明AF4是一种强大的DNA拓扑异构酶II催化抑制剂，这可能是促使细胞凋亡的一个合理原因。总体而言，我们的数据表明，AF4在体外具有比索拉非尼更强的抗增殖和特异性作用，是一种治疗肝癌的潜在天然化疗药物。
