A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3
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...
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doaj-7b2d53f28db64c61a7f47b82a8c015de2020-11-25T02:30:51ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-07-01167164011641310.3390/ijms160716401ijms160716401A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3Chenze Zhang0Wenqiang Yan1Bi Li2Bing Xu3Yan Gong4Fuhao Chu5Yuzhong Zhang6Qiuli Yao7Penglong Wang8Haimin Lei9School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, ChinaSchool of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, ChinaSchool of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, ChinaSchool of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, ChinaSchool of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, ChinaSchool of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, ChinaDepartment of Pathology, Beijing University of Chinese Medicine, Beijing 100102, ChinaSchool of Nursing, Beijing University of Chinese Medicine, Beijing 100102, ChinaSchool of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, ChinaSchool of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, ChinaA 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 4ʹ,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.http://www.mdpi.com/1422-0067/16/7/16401ligustrazine derivativeselective cytotoxicityhepatomaNF-κB/p65 and COX-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chenze Zhang Wenqiang Yan Bi Li Bing Xu Yan Gong Fuhao Chu Yuzhong Zhang Qiuli Yao Penglong Wang Haimin Lei |
spellingShingle |
Chenze Zhang Wenqiang Yan Bi Li Bing Xu Yan Gong Fuhao Chu Yuzhong Zhang Qiuli Yao Penglong Wang Haimin Lei A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3 International Journal of Molecular Sciences ligustrazine derivative selective cytotoxicity hepatoma NF-κB/p65 and COX-2 |
author_facet |
Chenze Zhang Wenqiang Yan Bi Li Bing Xu Yan Gong Fuhao Chu Yuzhong Zhang Qiuli Yao Penglong Wang Haimin Lei |
author_sort |
Chenze Zhang |
title |
A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3 |
title_short |
A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3 |
title_full |
A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3 |
title_fullStr |
A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3 |
title_full_unstemmed |
A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3 |
title_sort |
new ligustrazine derivative-selective cytotoxicity by suppression of nf-κb/p65 and cox-2 expression on human hepatoma cells. part 3 |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2015-07-01 |
description |
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 4ʹ,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. |
topic |
ligustrazine derivative selective cytotoxicity hepatoma NF-κB/p65 and COX-2 |
url |
http://www.mdpi.com/1422-0067/16/7/16401 |
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