全球約有 90% 的人感染 EB 病毒，而 EB 病毒主要感染人類的 B 淋胞細胞和上皮細胞，造成許多疾病。如：巴克氏淋巴瘤 (Burkitt’s lymphoma) 、霍奇金氏病 (Hodgkin’s lymphoma) 和鼻咽癌 (nasopharyngeal carcinoma) 等。先前實驗室發現虎杖乙酸乙酯分離物 F2a 會促進 B95-8 細胞中 EB 病毒潛伏期膜蛋白質 (LMP1) 及 EB 病毒核抗原 (EBNA1) 的表現，也能刺激 EB 病毒走向溶裂循環，使得含有 EB 病毒的腫瘤細胞內產生高濃度的活性氧物質 (ROS) ，進而誘發細胞凋亡。因此本研究將進一步探討 F2a 是否也能誘發人類 EB 病毒潛伏期第三型巴克氏淋巴瘤細胞 (Raji 細胞) ROS 產生使細胞走向凋亡。結果顯示 F2a 毒殺 Raji 細胞，其 CC 50 為 10.8 ug/ml 。 F2a 無法誘發 ROS 產生及 EB 溶裂循環，但是能藉由促進 EB 病毒潛伏膜蛋白質 1 表現，降低細胞內 p-IkBa/ IkBa 蛋白質比值，使 Caspase 3 活性及裂解 PARP 增加，導致 Raji 細胞凋亡。所以 F2a 可被開發為治療 EB 病毒相關腫瘤的潛在藥物。 Epstein-Barr virus (EBV) is a γ - herpesvirus that infects 90% of the adult human population. EBV infects lymphocyte and epitheial cells which leads to Burkitt’s lymphoma (BL) and Hodgkin’s lymphoma (HL) and nasopharyngeal carcinoma (NPC). Our earlier studies showed that the ethyl acetate subfraction F2a from Polygonum cuspidatum induces a high level of reactive oxygen species (ROS) and increase the expression of the EBV latent membrane protein 1 (LMP1), EBNA1 and lytic proteins which causes apoptosis of B95-8 cells. The purpose of this study is to investigate whether the subfraction F2a of ethyl acetate from Polygonum cuspidatum root induces apoptosis of EBV latency Ⅲ Burkitt's lymphoma (Raji cells) via a reactive oxygen species (ROS) mechanism. Results show that F2a kills Raji cells, at a CC50 values of 10.8 ug/ml. F2a although does not induce ROS production and EBV lytic cycle, F2a promots the expression of LMP1, reducing intracellular phospho-IkBa/ IkBa expression, which lead to a increased caspase 3 activity and cleavage of PARP to trigger apoptosis of Raji cells. Therefore, F2a can be developed as a therapeutic drug in the treatment of Epstein-Barr virus-related tumors.
