Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway
A series of novel furoxan-based NO-donating b-elemene hybrids were designed and synthesized to improve the anticancer efficacy of natural b-elemene. The bioassay results indicated that all of the target compounds exhibited significantly improved antiproliferative activities against three cancer cell...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Elsevier
2017
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| Online Access: | https://eprints.nottingham.ac.uk/42899/ |
| _version_ | 1848796596538441728 |
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| author | Chen, Jichao Wang, Tianyu Xu, Shengtao Zhang, Pengfei Lin, Aijun Wu, Liang Yao, Hequan Xie, Weijia Zhu, Zheying Xu, Jinyi |
| author_facet | Chen, Jichao Wang, Tianyu Xu, Shengtao Zhang, Pengfei Lin, Aijun Wu, Liang Yao, Hequan Xie, Weijia Zhu, Zheying Xu, Jinyi |
| author_sort | Chen, Jichao |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | A series of novel furoxan-based NO-donating b-elemene hybrids were designed and synthesized to improve the anticancer efficacy of natural b-elemene. The bioassay results indicated that all of the target compounds exhibited significantly improved antiproliferative activities against three cancer cell lines (SGC-7901, HeLa and U87) compared to parent compound b-elemene. Interestingly, these compounds displayed excellent sensitivity to U87 cells with IC50 values ranging from 173 to 2 nM. Moreover, most compounds produced high levels of NO in vitro, and the antitumor activity of 11a in U87 cells was markedly attenuated by an NO scavenger (hemoglobin or carboxy-PTIO). Further mechanism studies revealed that 11a caused the G2 phase arrest of the cell cycle and induced apoptosis of U87 cells by preventing the activation of the PI3K/Akt pathway. Moreover, 11a significantly suppressed the tumor growth in H22 liver cancer xenograft mouse model with a tumor inhibitory ratio (TIR) of 64.8%, which
was superior to that of b-elemene (TIR, 49.6%) at the same dose of 60 mg/kg. Together, the remarkable biological profiles of these novel NO-donating b-elemene derivatives may make them promising candidates for the intervention of human cancers. |
| first_indexed | 2025-11-14T19:50:30Z |
| format | Article |
| id | nottingham-42899 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:50:30Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-428992020-05-04T18:57:28Z https://eprints.nottingham.ac.uk/42899/ Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway Chen, Jichao Wang, Tianyu Xu, Shengtao Zhang, Pengfei Lin, Aijun Wu, Liang Yao, Hequan Xie, Weijia Zhu, Zheying Xu, Jinyi A series of novel furoxan-based NO-donating b-elemene hybrids were designed and synthesized to improve the anticancer efficacy of natural b-elemene. The bioassay results indicated that all of the target compounds exhibited significantly improved antiproliferative activities against three cancer cell lines (SGC-7901, HeLa and U87) compared to parent compound b-elemene. Interestingly, these compounds displayed excellent sensitivity to U87 cells with IC50 values ranging from 173 to 2 nM. Moreover, most compounds produced high levels of NO in vitro, and the antitumor activity of 11a in U87 cells was markedly attenuated by an NO scavenger (hemoglobin or carboxy-PTIO). Further mechanism studies revealed that 11a caused the G2 phase arrest of the cell cycle and induced apoptosis of U87 cells by preventing the activation of the PI3K/Akt pathway. Moreover, 11a significantly suppressed the tumor growth in H22 liver cancer xenograft mouse model with a tumor inhibitory ratio (TIR) of 64.8%, which was superior to that of b-elemene (TIR, 49.6%) at the same dose of 60 mg/kg. Together, the remarkable biological profiles of these novel NO-donating b-elemene derivatives may make them promising candidates for the intervention of human cancers. Elsevier 2017-07-28 Article PeerReviewed Chen, Jichao, Wang, Tianyu, Xu, Shengtao, Zhang, Pengfei, Lin, Aijun, Wu, Liang, Yao, Hequan, Xie, Weijia, Zhu, Zheying and Xu, Jinyi (2017) Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway. European Journal of Medicinal Chemistry, 135 . pp. 414-423. ISSN 1768-3254 β-Elemene; Furoxan; Antitumor activity; Apoptosis; PI3K/Akt pathway http://www.sciencedirect.com/science/article/pii/S0223523417303112 doi:10.1016/j.ejmech.2017.04.045 doi:10.1016/j.ejmech.2017.04.045 |
| spellingShingle | β-Elemene; Furoxan; Antitumor activity; Apoptosis; PI3K/Akt pathway Chen, Jichao Wang, Tianyu Xu, Shengtao Zhang, Pengfei Lin, Aijun Wu, Liang Yao, Hequan Xie, Weijia Zhu, Zheying Xu, Jinyi Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway |
| title | Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway |
| title_full | Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway |
| title_fullStr | Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway |
| title_full_unstemmed | Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway |
| title_short | Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway |
| title_sort | discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the pi3k/akt pathway |
| topic | β-Elemene; Furoxan; Antitumor activity; Apoptosis; PI3K/Akt pathway |
| url | https://eprints.nottingham.ac.uk/42899/ https://eprints.nottingham.ac.uk/42899/ https://eprints.nottingham.ac.uk/42899/ |