Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai 981-8553, Japan.
Oncol Rep. 2012 Jan;27(1):204-9. doi: 10.3892/or.2011.1498. Epub 2011 Oct 12.
Flavonoids are naturally occurring antioxidants, with several flavonoids shown to have chemopreventive effects on cancer. We investigated the effects of the flavonoid acacetin on human T cell leukemia Jurkat cells. Acacetin inhibited the proliferation of Jurkat cells by inducing apoptosis in a concentration- and time-dependent manner. Acacetin-induced cell death was characterized by changes in nuclear and cell morphology. Treatment of Jurkat cells with acacetin also induced caspase-3, -8 and -9 activities in a time-dependent manner. Acacetin-induced apoptosis was blocked by a broad-spectrum caspase inhibitor, a caspase-3 inhibitor and a caspase-8 inhibitor, but not by a caspase-9 inhibitor. In addition, acacetin promoted the expression of FAF1, phosphor-FADD, Apaf-1 and cytochrome c. Acacetin-induced apoptosis was also accompanied by upregulation of Bax, and downregulation of Bcl-2. Taken together, these results suggest that acacetin may induce apoptosis in T cell leukemia cells, possibly by activating the Fas-mediated pathway. These findings may help in designing cancer therapeutic and chemopreventive agents.
类黄酮是天然存在的抗氧化剂，已有几种类黄酮显示出对癌症的化学预防作用。我们研究了类黄酮 Acacetin 对人 T 细胞白血病 Jurkat 细胞的影响。Acacetin 通过诱导细胞凋亡，以浓度和时间依赖的方式抑制 Jurkat 细胞的增殖。Acacetin 诱导的细胞死亡的特征是核和细胞形态的变化。用 Acacetin 处理 Jurkat 细胞也会诱导 caspase-3、-8 和 -9 活性的时间依赖性增加。Acacetin 诱导的细胞凋亡被广谱 caspase 抑制剂、caspase-3 抑制剂和 caspase-8 抑制剂阻断，但 caspase-9 抑制剂不阻断。此外，Acacetin 还促进了 FAF1、磷酸化 FADD、Apaf-1 和细胞色素 c 的表达。Acacetin 诱导的细胞凋亡也伴随着 Bax 的上调和 Bcl-2 的下调。总之，这些结果表明 Acacetin 可能通过激活 Fas 介导的途径诱导 T 细胞白血病细胞凋亡。这些发现可能有助于设计癌症治疗和化学预防剂。
