Tzeng Cheng-Wei, Tzeng Wen-Sheng, Lin Liang-Tzung, Lee Chiang-Wen, Yen Ming-Hong, Yen Feng-Lin, Lin Chun-Ching
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
Am J Chin Med. 2015;43(3):559-79. doi: 10.1142/S0192415X15500354.
For centuries, natural plant extracts have played an important role in traditional medicine for curing and preventing diseases. Studies have revealed that Artocarpus communis possess various bioactivities, such as anti-inflammation, anti-oxidant, and anticancer activities. A. communis offers economic value as a source of edible fruit, yields timber, and is widely used in folk medicines. However, little is known about its molecular mechanisms of anticancer activity. Here, we demonstrate the antiproliferative activity of A. communis methanol extract (AM) and its dichloromethane fraction (AD) in two human hepatocellular carcinoma (HCC) cell lines, HepG2 and PLC/PRF/5. Colony assay showed the long-term inhibitory effect of both extracts on cell growth. DNA laddering and immunoblotting analyses revealed that both extracts did not induce apoptosis in the hepatoma cell lines. AM and AD-treated cells demonstrated different cell cycle distribution compared to UV-treated cells, which presented apoptotic cell death with high sub-G1 ratio. Instead, acridine orange staining revealed that AM and AD triggered autophagosome accumulation. Immunoblotting showed a significant expression of autophagy-related proteins, which indicated the autophagic cell death (ACD) of hepatoma cell lines. This study therefore demonstrates that A. communis AM and its dichloromethane fraction can induce ACD in HCC cells and elucidates the potential of A. communis extracts for development as anti tumor therapeutic agents that utilize autophagy as mechanism in mediating cancer cell death.
几个世纪以来，天然植物提取物在传统医学的疾病治疗和预防中发挥了重要作用。研究表明，面包树具有多种生物活性，如抗炎、抗氧化和抗癌活性。面包树作为可食用水果的来源具有经济价值，可产出木材，并且在民间药物中广泛使用。然而，其抗癌活性的分子机制却鲜为人知。在此，我们展示了面包树甲醇提取物（AM）及其二氯甲烷馏分（AD）对两种人类肝癌（HCC）细胞系HepG2和PLC/PRF/5的抗增殖活性。集落测定显示两种提取物对细胞生长均有长期抑制作用。DNA梯状条带分析和免疫印迹分析表明，两种提取物均未诱导肝癌细胞系凋亡。与紫外线处理的细胞相比，AM和AD处理的细胞表现出不同的细胞周期分布，紫外线处理的细胞呈现出高亚G1比例的凋亡细胞死亡。相反，吖啶橙染色显示AM和AD触发了自噬体积累。免疫印迹显示自噬相关蛋白的显著表达，这表明肝癌细胞系发生了自噬性细胞死亡（ACD）。因此，本研究表明面包树AM及其二氯甲烷馏分可诱导肝癌细胞发生自噬性细胞死亡，并阐明了面包树提取物作为利用自噬作为介导癌细胞死亡机制的抗肿瘤治疗药物的开发潜力。
