title: A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3.
abstract: A new anticancer ligustrazine derivative, 3β-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-κB/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 µM) 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 µM). 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-κB/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-κB/p65 and COX-2.
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. zcz920418@163.com.
authors.forename: Chenze
authors.initials: C
authors.lastname: Zhang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. ywq3226925@163.com.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Yan
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. libimegan@163.com.
authors.forename: Bi
authors.initials: B
authors.lastname: Li
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. weichenxubing@126.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. gongyan90@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. chufhao@163.com.
authors.forename: Fuhao
authors.initials: F
authors.lastname: Chu
authors.affiliation: Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China. zyz100102@126.com.
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Nursing, Beijing University of Chinese Medicine, Beijing 100102, China. yaoqiuli2008@163.com.
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Yao
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. wpl581@126.com.
authors.forename: Penglong
authors.initials: P
authors.lastname: Wang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. leihaimin@126.com.
authors.forename: Haimin
authors.initials: H
authors.lastname: Lei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D011719:Pyrazines / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D011719:Pyrazines; D051996:Transcription Factor RelA; D051546:Cyclooxygenase 2; C017953:tetramethylpyrazine
keywords: NF-κB/p65 and COX-2; hepatoma; ligustrazine derivative; selective cytotoxicity