A novel pyrrolidine-2,5-dione derivative induced G2/M phase arrest and apoptosis of hepatocellular carcinoma HepG2 cells through inhibiting tubulin polymerization
Hepatocellular carcinoma (HCC) is a major global cause of carcinoma-related fatality. The inhibition of tubulin polymerization holds significant potential in the development of cancer drugs. In our study, we synthesized a novel pyrrolidine-2,5-dione derivative (compound 8) that exhibited potent anti...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535223010122 |
| _version_ | 1797356106681417728 |
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| author | Yingying Tian Ailin Yang Huiming Huang Jinxin Xie Longyan Wang Dongxiao Liu Xuejiao Wei Peng Tan Pengfei Tu Dongjun Fu Zhongdong Hu |
| author_facet | Yingying Tian Ailin Yang Huiming Huang Jinxin Xie Longyan Wang Dongxiao Liu Xuejiao Wei Peng Tan Pengfei Tu Dongjun Fu Zhongdong Hu |
| author_sort | Yingying Tian |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is a major global cause of carcinoma-related fatality. The inhibition of tubulin polymerization holds significant potential in the development of cancer drugs. In our study, we synthesized a novel pyrrolidine-2,5-dione derivative (compound 8) that exhibited potent anti-HCC activity (IC50 value of 2.082 μM) against human HCC HepG2 cells. Moreover, compound 8 significantly suppressed the HepG2 cell multiplication, and triggered G2/M phase arrest of HepG2 cells and their apoptosis. Further mechanistic investigations revealed that compound 8 suppressed tubulin polymerization by directly binding to the colchicine binding site of β-tubulin. Additionally, compound 8 significantly inhibited tumor growth with low toxicity in nude HepG2 tumor-bearing mice, achieving an approximate inhibition rate of 45.73 %. Therefore, compound 8 represents a promising pharmaceutical candidate for HCC management. |
| first_indexed | 2024-03-08T14:20:50Z |
| format | Article |
| id | doaj.art-233dc90ca6da49c782bc5eb374252ad8 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-03-08T14:20:50Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-233dc90ca6da49c782bc5eb374252ad82024-01-14T05:37:55ZengElsevierArabian Journal of Chemistry1878-53522024-02-01172105550A novel pyrrolidine-2,5-dione derivative induced G2/M phase arrest and apoptosis of hepatocellular carcinoma HepG2 cells through inhibiting tubulin polymerizationYingying Tian0Ailin Yang1Huiming Huang2Jinxin Xie3Longyan Wang4Dongxiao Liu5Xuejiao Wei6Peng Tan7Pengfei Tu8Dongjun Fu9Zhongdong Hu10School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, ChinaBeijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; Corresponding authors at: No. 11 North 3rd Ring East Road, Chaoyang District, Beijing 100029, PR China.Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; Corresponding authors at: No. 11 North 3rd Ring East Road, Chaoyang District, Beijing 100029, PR China.Hepatocellular carcinoma (HCC) is a major global cause of carcinoma-related fatality. The inhibition of tubulin polymerization holds significant potential in the development of cancer drugs. In our study, we synthesized a novel pyrrolidine-2,5-dione derivative (compound 8) that exhibited potent anti-HCC activity (IC50 value of 2.082 μM) against human HCC HepG2 cells. Moreover, compound 8 significantly suppressed the HepG2 cell multiplication, and triggered G2/M phase arrest of HepG2 cells and their apoptosis. Further mechanistic investigations revealed that compound 8 suppressed tubulin polymerization by directly binding to the colchicine binding site of β-tubulin. Additionally, compound 8 significantly inhibited tumor growth with low toxicity in nude HepG2 tumor-bearing mice, achieving an approximate inhibition rate of 45.73 %. Therefore, compound 8 represents a promising pharmaceutical candidate for HCC management.http://www.sciencedirect.com/science/article/pii/S1878535223010122Pyrrolidine-2,5-dione derivativeHepatocellular carcinomaProliferationG2/M phase arrestApoptosisTubulin polymerization |
| spellingShingle | Yingying Tian Ailin Yang Huiming Huang Jinxin Xie Longyan Wang Dongxiao Liu Xuejiao Wei Peng Tan Pengfei Tu Dongjun Fu Zhongdong Hu A novel pyrrolidine-2,5-dione derivative induced G2/M phase arrest and apoptosis of hepatocellular carcinoma HepG2 cells through inhibiting tubulin polymerization Arabian Journal of Chemistry Pyrrolidine-2,5-dione derivative Hepatocellular carcinoma Proliferation G2/M phase arrest Apoptosis Tubulin polymerization |
| title | A novel pyrrolidine-2,5-dione derivative induced G2/M phase arrest and apoptosis of hepatocellular carcinoma HepG2 cells through inhibiting tubulin polymerization |
| title_full | A novel pyrrolidine-2,5-dione derivative induced G2/M phase arrest and apoptosis of hepatocellular carcinoma HepG2 cells through inhibiting tubulin polymerization |
| title_fullStr | A novel pyrrolidine-2,5-dione derivative induced G2/M phase arrest and apoptosis of hepatocellular carcinoma HepG2 cells through inhibiting tubulin polymerization |
| title_full_unstemmed | A novel pyrrolidine-2,5-dione derivative induced G2/M phase arrest and apoptosis of hepatocellular carcinoma HepG2 cells through inhibiting tubulin polymerization |
| title_short | A novel pyrrolidine-2,5-dione derivative induced G2/M phase arrest and apoptosis of hepatocellular carcinoma HepG2 cells through inhibiting tubulin polymerization |
| title_sort | novel pyrrolidine 2 5 dione derivative induced g2 m phase arrest and apoptosis of hepatocellular carcinoma hepg2 cells through inhibiting tubulin polymerization |
| topic | Pyrrolidine-2,5-dione derivative Hepatocellular carcinoma Proliferation G2/M phase arrest Apoptosis Tubulin polymerization |
| url | http://www.sciencedirect.com/science/article/pii/S1878535223010122 |
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