选择性杀伤肿瘤细胞而减轻对正常组织的损伤是目前治疗肿瘤策略所面临的重大挑战。研究表明，由于肿瘤细胞的快速增殖，实体瘤细胞通常处于氧气、葡萄糖或其他营养物质匮乏的状态。因此，靶向葡萄糖缺乏的肿瘤细胞可能会成为选择性杀伤肿瘤细胞的一个新策略。
牛蒡子苷元是临床常用传统中药牛蒡子的主要活性成分。现有研究表明，牛蒡子苷元具有抗肿瘤活性，能够在多种肿瘤模型中有效抑制肿瘤生长。中科院上海药物研究所俞强课题组对牛蒡子苷元的抗肿瘤机制进行了深入研究，发现在葡萄糖缺乏条件下，牛蒡子苷元通过抑制线粒体呼吸造成肿瘤细胞内ATP水平下降以及活性氧族水平升高，从而促使肿瘤细胞死亡。
研究同时还发现，牛蒡子苷元和糖酵解抑制剂2-脱氧-D-葡萄糖联合使用能够选择性杀伤肿瘤细胞，而对正常细胞的毒性较低。
该项研究成果为用中药治疗肿瘤提供了新的依据和策略。相关论文已在线发表于Biochemical Pharmacology杂志。
该研究工作得到了国家自然科学基金和国家重大科技专项的资助。(生物谷Bioon.com）
doi.org/10.1016/j.bcp.2012.06.002
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Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism
Yuan Gua， Chunting Qia， Xiaoxiao Suna， Xiuquan Mab， Haohao Zhanga， Lihong Huc， Junying Yuand， Qiang Yua，
a Department of Tumor Pharmacology， Shanghai Institute of Materia Medica， Chinese Academy of Sciences， Shanghai， China
b Department of Bioorganic Chemistry， Shanghai Institute of Organic Chemistry， Chinese Academy of Sciences， Shanghai， China
c State Key Laboratory of Drug Research， Shanghai Institute of Materia Medica， Chinese Academy of Sciences， Shanghai， China
d Department of Cell Biology， Harvard Medical School， Boston， USA
Abstract
Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study， we investigated the function and molecular mechanisms of a natural compound， arctigenin， in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so， arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore， we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly， this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence， we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity.
