A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-kappa B/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3

作者：Zhang Chenze; Yan Wenqiang; Li Bi; Xu Bing; Gong Yan; Chu Fuhao; Zhang Yuzhong; Yao Qiuli; Wang Penglong^*; Lei Haimin

来源：International Journal of Molecular Sciences, 2015, 16(7): 16401-16413.

DOI：10.3390/ijms160716401

• ligustrazine derivative
• selective cytotoxicity
• hepatoma
• NF-kappa B
• p65 and COX-2

A new anticancer ligustrazine derivative, 3-hydroxyolea-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methylester (T-OA, C38H58O3N2), was previously reported. It was synthesized via conjugating hepatoprotective and anticancer ingredients of traditional Chinese medicine. We found that T-OA exerted its anticancer activity by preventing the expression of nuclear transcription factor NF-B/p65 and COX-2 in S180 mice. However, the selective cytotoxicity of T-OA on various kinds of cell lines has not been studied sufficiently. In the present study, compared with Cisplatin, T-OA was more toxic to human hepatoma cell line Bel-7402 (IC50 = 6.36 +/- 1.56 mu M) than other three cancer cell lines (HeLa, HT-29, BGC-823), and no toxicity was observed toward Madin-Darby canine kidney cell line MDCK (IC50 > 150 mu M). The morphological changes of Bel-7402 cells demonstrated that T-OA had an apoptosis-inducing effect which had been substantiated using 4',6-diamidino-2-phenylindole (DAPI) staining, acridine orange (AO)/ethidium bromide (EB) staining, flow cytometry and mitochondrial membrane potential assay. Combining the immumohistochemical staining, we found T-OA could prevent the expression of NF-B/p65 and COX-2 in Bel-7402 cells. Both of the proteins have been known to play roles in apoptosis and are mainly located in the nuclei. Moreover subcellular localization was performed to reveal that T-OA exerts in nuclei of Bel-7402 cells. The result was in accordance with the effects of down-regulating the expression of NF-B/p65 and COX-2.

• 出版日期2015-7
• 单位北京中医药大学