Skip to main content

ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1496131
This article is part of the Research Topic The Role of Cannabinoids and the Endocannabinoid System in Anti-Cancer Therapy View all articles

Cytotoxicity of Natural and Synthetic Cannabinoids and Their Synergistic Antiproliferative Effects with Cisplatin in Human Ovarian Cancer Cells

Provisionally accepted
Ying Chen Ying Chen 1,2Huifang Li Huifang Li 1Jia Liu Jia Liu 2Jie Ni Jie Ni 2Qicheng Deng Qicheng Deng 2Haotian He Haotian He 1Panpan Wu Panpan Wu 3Yinsheng Wan Yinsheng Wan 4Navindra P Seeram Navindra P Seeram 1Chang Liu Chang Liu 1Hang Ma Hang Ma 1*Weipei Zhu Weipei Zhu 2
  • 1 University of Rhode Island, Kingston, United States
  • 2 Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
  • 3 School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, China
  • 4 Providence College, Providence, Rhode Island, United States

The final, formatted version of the article will be published soon.

    Cannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects. Herein, an investigation into the antiproliferative effects of cannabinoids on human ovarian cancer Caov-3 cells identified cannabidiol (CBD) as the most promising compound. Furthermore, chemical modifications of CBD yielded a group of derivatives with enhanced cytotoxicity in Caov-3 cells. Two 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 (at 5 µM) combined with cisplatin (1 µM) showed 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. Findings 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.

    Keywords: Cannabinoids, Cannabidiol, ovarian cancer, synergistic effect, Cisplatin

    Received: 13 Sep 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Chen, Li, Liu, Ni, Deng, He, Wu, Wan, Seeram, Liu, Ma and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hang Ma, University of Rhode Island, Kingston, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.