Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells
Roburic acid (ROB) is a naturally occurred tetracyclic triterpenoid, and the anticancer activity of this compound has not been reported. Docetaxel (DOC) is the first-line chemotherapeutic agent for advanced stage prostate cancer but toxic side effects and drug resistance limit its clinical success....
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2021.2018684 |
| _version_ | 1818754748380086272 |
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| author | Xiao Wang Xu Xuetao Mengshuo Wu Panpan Wu Zhaojun Sheng Wenfeng Liu Yan-Yan Ma Den-Gao Zhao Kun Zhang Dongli Li Xi Zheng Susan Goodin |
| author_facet | Xiao Wang Xu Xuetao Mengshuo Wu Panpan Wu Zhaojun Sheng Wenfeng Liu Yan-Yan Ma Den-Gao Zhao Kun Zhang Dongli Li Xi Zheng Susan Goodin |
| author_sort | Xiao Wang |
| collection | DOAJ |
| description | Roburic acid (ROB) is a naturally occurred tetracyclic triterpenoid, and the anticancer activity of this compound has not been reported. Docetaxel (DOC) is the first-line chemotherapeutic agent for advanced stage prostate cancer but toxic side effects and drug resistance limit its clinical success. In this study, the potential synergistic anticancer effect and the underlying mechanisms of ROB in combination with DOC on prostate cancer were investigated. The results showed that ROB and DOC in combination synergistically inhibited the growth of prostate cancer cells. The combination also strongly induced apoptosis, and suppressed cell migration, invasion and sphere formation. Mechanistic study showed that the combined effects of ROB and DOC on prostate cancer cells were associated with inhibition of NF-κB activation, down regulation of Bcl-2 and up regulation of Bax. Knockdown of NF-κB by small interfering RNA (siRNA) significantly decreased the combined effect of ROB and DOC. Moreover, we found that esomeprazole (ESOM), a proton pump inhibitor (PPI), strongly enhanced the effectiveness of ROB and DOC on prostate cancer cells in acidic culture medium. Since acidic micro environment is known to impair the efficacy of current anticancer therapies, ESOM combined with ROB and DOC may be an effective approach for improving the treatment of prostate cancer patients. |
| first_indexed | 2024-12-18T05:28:11Z |
| format | Article |
| id | doaj.art-eeecfaf69d4d4338a53e198ba3ebce48 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-18T05:28:11Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-eeecfaf69d4d4338a53e198ba3ebce482022-12-21T21:19:30ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-0137154255310.1080/14756366.2021.20186842018684Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cellsXiao Wang0Xu Xuetao1Mengshuo Wu2Panpan Wu3Zhaojun Sheng4Wenfeng Liu5Yan-Yan Ma6Den-Gao Zhao7Kun Zhang8Dongli Li9Xi Zheng10Susan Goodin11School of Biotechnology and Health Sciences, Wuyi UniversitySchool of Biotechnology and Health Sciences, Wuyi UniversitySchool of Biotechnology and Health Sciences, Wuyi UniversitySchool of Biotechnology and Health Sciences, Wuyi UniversitySchool of Biotechnology and Health Sciences, Wuyi UniversitySchool of Biotechnology and Health Sciences, Wuyi UniversitySchool of Biotechnology and Health Sciences, Wuyi UniversitySchool of Biotechnology and Health Sciences, Wuyi UniversitySchool of Biotechnology and Health Sciences, Wuyi UniversitySchool of Biotechnology and Health Sciences, Wuyi UniversityDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New JerseyRutgers Cancer Institute of New JerseyRoburic acid (ROB) is a naturally occurred tetracyclic triterpenoid, and the anticancer activity of this compound has not been reported. Docetaxel (DOC) is the first-line chemotherapeutic agent for advanced stage prostate cancer but toxic side effects and drug resistance limit its clinical success. In this study, the potential synergistic anticancer effect and the underlying mechanisms of ROB in combination with DOC on prostate cancer were investigated. The results showed that ROB and DOC in combination synergistically inhibited the growth of prostate cancer cells. The combination also strongly induced apoptosis, and suppressed cell migration, invasion and sphere formation. Mechanistic study showed that the combined effects of ROB and DOC on prostate cancer cells were associated with inhibition of NF-κB activation, down regulation of Bcl-2 and up regulation of Bax. Knockdown of NF-κB by small interfering RNA (siRNA) significantly decreased the combined effect of ROB and DOC. Moreover, we found that esomeprazole (ESOM), a proton pump inhibitor (PPI), strongly enhanced the effectiveness of ROB and DOC on prostate cancer cells in acidic culture medium. Since acidic micro environment is known to impair the efficacy of current anticancer therapies, ESOM combined with ROB and DOC may be an effective approach for improving the treatment of prostate cancer patients.http://dx.doi.org/10.1080/14756366.2021.2018684prostate cancerroburic aciddocetaxelcombination |
| spellingShingle | Xiao Wang Xu Xuetao Mengshuo Wu Panpan Wu Zhaojun Sheng Wenfeng Liu Yan-Yan Ma Den-Gao Zhao Kun Zhang Dongli Li Xi Zheng Susan Goodin Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells Journal of Enzyme Inhibition and Medicinal Chemistry prostate cancer roburic acid docetaxel combination |
| title | Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells |
| title_full | Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells |
| title_fullStr | Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells |
| title_full_unstemmed | Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells |
| title_short | Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells |
| title_sort | inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells |
| topic | prostate cancer roburic acid docetaxel combination |
| url | http://dx.doi.org/10.1080/14756366.2021.2018684 |
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