Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells
IntroductionCannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects.MethodsHerein, an investigation into the antiproliferative effects of natural cannabinoids on human ovarian cancer Caov-3 cells...
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Frontiers Media S.A.
2024-11-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1496131/full |
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| author | Ying Chen Ying Chen Huifang Li Jia Liu Jie Ni Qicheng Deng Haotian He Panpan Wu Yinsheng Wan Navindra P. Seeram Chang Liu Hang Ma Weipei Zhu |
| author_facet | Ying Chen Ying Chen Huifang Li Jia Liu Jie Ni Qicheng Deng Haotian He Panpan Wu Yinsheng Wan Navindra P. Seeram Chang Liu Hang Ma Weipei Zhu |
| author_sort | Ying Chen |
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| description | IntroductionCannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects.MethodsHerein, an investigation into the antiproliferative effects of natural cannabinoids on human ovarian cancer Caov-3 cells identified cannabidiol (CBD) as the most promising cannabinoid. Furthermore, chemical modifications of CBD yielded a group of derivatives with enhanced cytotoxicity in Caov-3 cells.ResultsTwo CBD piperazinyl derivatives (19 and 21) showed augmented antiproliferative effects with an IC50 of 5.5 and 4.1 µM, respectively, compared to CBD’s IC50 of 22.9 µM. Further studies suggest that modulation of apoptosis and ferroptosis may contribute to the cytotoxic effects of CBD and its derivatives. In addition, CBD and its derivatives (19 and 21) were explored for their potential synergistic antiproliferative effects in combination with chemotherapeutic agent cisplatin. Compounds 19 or 21 (5 µM) combined with cisplatin (1 µM) showed a synergistic effect with a combination index of 0.23 and 0.72, respectively. This effect was supported by elevated levels of reactive oxygen species in Caov-3 cells treated with cisplatin combined with 19 or 21.DiscussionFindings from this study suggest that CBD derivatives with enhanced antiproliferative effects may exert synergistic effects with chemotherapeutic drugs, providing insight into the development of cannabinoid-based adjuvant agents for the management of ovarian cancer. |
| format | Article |
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| issn | 1663-9812 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-c3e4790a02bc45f4b2d49606d188917c2025-08-20T02:23:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-11-011510.3389/fphar.2024.14961311496131Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cellsYing Chen0Ying Chen1Huifang Li2Jia Liu3Jie Ni4Qicheng Deng5Haotian He6Panpan Wu7Yinsheng Wan8Navindra P. Seeram9Chang Liu10Hang Ma11Weipei Zhu12Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaBioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, United StatesBioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, United StatesDepartment of Operation Room, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaBioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, United StatesGuangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, ChinaDepartment of Biology, Providence College, Providence, RI, United StatesBioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, United StatesBioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, United StatesBioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, United StatesDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaIntroductionCannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects.MethodsHerein, an investigation into the antiproliferative effects of natural cannabinoids on human ovarian cancer Caov-3 cells identified cannabidiol (CBD) as the most promising cannabinoid. Furthermore, chemical modifications of CBD yielded a group of derivatives with enhanced cytotoxicity in Caov-3 cells.ResultsTwo CBD piperazinyl derivatives (19 and 21) showed augmented antiproliferative effects with an IC50 of 5.5 and 4.1 µM, respectively, compared to CBD’s IC50 of 22.9 µM. Further studies suggest that modulation of apoptosis and ferroptosis may contribute to the cytotoxic effects of CBD and its derivatives. In addition, CBD and its derivatives (19 and 21) were explored for their potential synergistic antiproliferative effects in combination with chemotherapeutic agent cisplatin. Compounds 19 or 21 (5 µM) combined with cisplatin (1 µM) showed a synergistic effect with a combination index of 0.23 and 0.72, respectively. This effect was supported by elevated levels of reactive oxygen species in Caov-3 cells treated with cisplatin combined with 19 or 21.DiscussionFindings from this study suggest that CBD derivatives with enhanced antiproliferative effects may exert synergistic effects with chemotherapeutic drugs, providing insight into the development of cannabinoid-based adjuvant agents for the management of ovarian cancer.https://www.frontiersin.org/articles/10.3389/fphar.2024.1496131/fullcannabinoidscannabidiolovarian cancersynergistic effectcisplatin |
| spellingShingle | Ying Chen Ying Chen Huifang Li Jia Liu Jie Ni Qicheng Deng Haotian He Panpan Wu Yinsheng Wan Navindra P. Seeram Chang Liu Hang Ma Weipei Zhu Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells Frontiers in Pharmacology cannabinoids cannabidiol ovarian cancer synergistic effect cisplatin |
| title | Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells |
| title_full | Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells |
| title_fullStr | Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells |
| title_full_unstemmed | Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells |
| title_short | Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells |
| title_sort | cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells |
| topic | cannabinoids cannabidiol ovarian cancer synergistic effect cisplatin |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1496131/full |
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