Zhu Wenhe, Liu Lei, Dong Yuan, Meng Guixian, Tang Lu, Li Yan, Cai Jianhui, Wang Huiyan
Jilin Medical University Jilin 132013 China
RSC Adv. 2019 Mar 21;9(16):9281-9288. doi: 10.1039/c8ra09967g. eCollection 2019 Mar 15.
T-2 toxin, produced by moulds, is a type A trichothecene mycotoxin which is known to inhibit protein synthesis and also reported to induce DNA lesions, potentially causing DNA fragmentation. T-2 toxin is a very potent cytotoxic toxin, which displays anti-tumor properties. Nevertheless, more studies are still needed to explore its antitumor mechanisms as well as its clinical application in cancer treatment. Here, we report the identification and characterization of a T-2 toxin produced by a isolated from Jilin, Northeast China. 17 strains of were screened for T-2 toxin-production and one strain with the highest yield was selected further studies. T-2 toxin produced by the selected was isolated and purified by HPLC. Anticancer properties of the purified T-2 toxin were evaluated with human hepatoma cell SMMC-7721. The purified T-2 toxin inhibits the proliferation of SMMC-7721 cells and induces cell apoptosis. The mitochondrial membrane potential decreased and the intracellular ROS was up-regulated after T-2 treatment of the cells. Further studies revealed that T-2 treatment activates the intrinsic mitochondrial and MAPKs pathway. Our data provide insight into the promising application of the T-2 toxin in cancer treatment.
由霉菌产生的T-2毒素是一种A类单端孢霉烯族霉菌毒素，已知其可抑制蛋白质合成，也有报道称其会诱导DNA损伤，可能导致DNA片段化。T-2毒素是一种非常有效的细胞毒性毒素，具有抗肿瘤特性。然而，仍需要更多研究来探索其抗肿瘤机制以及在癌症治疗中的临床应用。在此，我们报告了从中国东北吉林分离出的一株霉菌所产生的T-2毒素的鉴定和特性。筛选了17株霉菌的T-2毒素产生情况，并选择了一株产量最高的菌株进行进一步研究。通过高效液相色谱法（HPLC）分离和纯化所选霉菌产生的T-2毒素。用人类肝癌细胞SMMC-7721评估纯化后的T-2毒素的抗癌特性。纯化后的T-2毒素抑制SMMC-7721细胞的增殖并诱导细胞凋亡。用T-2处理细胞后，线粒体膜电位降低，细胞内活性氧（ROS）上调。进一步研究表明，T-2处理激活了内在线粒体和丝裂原活化蛋白激酶（MAPKs）途径。我们的数据为T-2毒素在癌症治疗中的应用前景提供了见解。
