耳壳藻内酯分子合成及其抗肿瘤活性的研究  

STUDIES ON ANTI-NEOPLASTIC CONSTITUENTS FROM CAULILIDE AND LACTONE AND THEIR MOLECULAR SYNTHESIS

作　　者：张擎[1] 邓宁[2] 贺国安[3] 刘红霞[4] 唐小江 

机构地区：[1]中山大学教育部基因工程重点实验室,510275 [2]暨南大学生物工程系,广东广州510632 [3]中山大学肿瘤医院,广东广州510060 [4]中山大学化工学院,广东广州510275 [5]广东省职业病防治中心,广东广州510405

出　　处：《热带海洋学报》2004年第3期1-5,共5页Journal of Tropical Oceanography

基　　金：国家自然科学基金(29672053);国家教育委员会博士学科点专项基金(960103)

摘　　要：采用四甲基偶氮唑盐(MTT)法体外肿瘤细胞株抑制试验,研究耳壳藻内酯合成过程中结构的衍化物和抗肿瘤活性的关系。结果表明,耳壳藻内酯对小鼠肝细胞癌(H22)、小鼠路易斯肺癌(LLC)、人宫颈癌(Hela)和人乳腺癌(MCF-7)有较强的细胞毒性,对正常小鼠胚成纤维(NIH3T3)和人肝细胞(L-02)的毒性较低。酮基内酯对各肿瘤细胞毒性差异较大,对上述正常细胞株的杀伤力也较大。体外结合DNA的研究表明,耳壳藻内酯芳香环上的羟基较酮基内酯上的酮基易于插入DNA分子中,造成DNA分子的断裂和解聚。标记代谢物前体掺入试验表明,耳壳藻内酯能够显著抑制DNA大分子的合成,阻滞肿瘤细胞的生长。推测耳壳藻内酯芳香环上的羟基是影响其抗肿瘤活性的主要官能团。The screening of active compounds was guided by MTT(3-(4,5-dimethylthia-zal-2yl)2, 5-diphenyltetrazolium bromide) bioassay methods. The results showed that caulilide had remarkable in vitro inhibition against the tumor cell lines of LLC, H22, Hela and MCF-7, but had low cytotoxic activity against normal cell lines of L-02 and NIH3T3. Lactone showed wide cytotoxic differences against different tumor cells and had strong cytotoxic activity against the above normal cells. DNA interaction indicated that the hydroxyl in aromatic ring of caulilide was easier to be inserted in DNA chains than the ketone of lactone, resulting in break of DNA chains. Furthermore, 3H-TdR in-corporation showed caulilide could significantly inhibit the DNA synthesis in H22 cell lines in dose-dependent manner and retard tumor cell growth. These results suggested that anti-tumor activities of caulilide compounds are related to the hydroxyls in its aromatic ring.

关 键 词：耳壳藻内酯 酮基内酯 细胞毒性 DNA断裂 DNA合成 

分 类 号：R282.77[医药卫生—中药学] R284.3[医药卫生—中医学]