Efficacy of Cannabidiol Combination with Cisplatin or Paclitaxel against Platinum-Resistant Ovarian Cancer Cell Lines

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dc.contributor.author Ismail, Jana
dc.date.accessioned 2022-07-28T05:51:08Z
dc.date.available 2022-07-28T05:51:08Z
dc.date.copyright 2022 en_US
dc.date.issued 2022-05-13
dc.identifier.uri http://hdl.handle.net/10725/13889
dc.description.abstract Cannabidiol (CBD) is one of the most abundant and commonly used cannabinoid of the Cannabis plant. Unlike tetrahydrocannabinol (THC), it lacks psychoactive properties, and thus it is considered to be a uniquely attractive cannabinoid for study. It has been used to treat various ailments, including epilepsy, anxiety, psychosis, inflammation, and cancer. Various in vitro, and to a lesser extent in vivo, studies have demonstrated the anti-cancer activity of CBD on different cancer cell types, and a few others showed that combining CBD with different chemotherapeutic agents exhibited variable interactions, ranging from antagonism, additive effect, and synergism. Few studies examined the anticancer activity of CBD, as well as its combination with cisplatin or paclitaxel, on ovarian cancer. Hence, the current study aimed to evaluate the anti-cancer activity of CBD, extracted from Lebanese Cannabis sativa plant, as monotherapy and in combination with conventional chemotherapeutic drugs cisplatin or paclitaxel on human ovarian adenocarcinoma OVCAR-3 and SK-OV-3 cell lines. CBD was extracted by Liquid Column Chromatography and confirmed by GC-MS. Cell survival was evaluated using the MTS cell proliferation assay. Monotherapy with CBD demonstrated a dose-dependent tumor growth inhibition at 72h, with the IC50 being 12.5 μg/ml for OVCAR-3 cell line and 12.3 μg/ml for SK-OV-3 cell line. The IC50 of cisplatin against OVCAR-3 and SK-OV-3 cell lines (1.1 and 3.3 μg/ml, respectively), and that of paclitaxel against SK-OV-3 cell line (9.9 μg/ml) were obtained as well. Additionally, applying the Chou-Talalay method using the CompuSyn software, the combination indexes (CI) were calculated to predict the interaction between CBD and the chemotherapeutic agents. The combination of CBD with either cisplatin or paclitaxel exhibited a significant antagonistic interaction against SK-OV-3 cell line when compared to individual treatment (CI > 1). However, at high cell growth inhibition rates (95% and 97%), mild synergism is detected (CI < 1) when combining CBD with cisplatin against this specific cell line. Thus, according to Drug Reduction Index (DRI), a combination of 6-fold less concentration of cisplatin with 1.3-fold less concentration of CBD yields a 95% cell growth inhibition. This synergistic interaction was confirmed in an in vitro experimentation setting. Pure antagonism was detected however when combining CBD and cisplatin against OVCAR-3 cell line. Evaluating the effect of CBD combined with paclitaxel against SK-OV-3 cell line demonstrated antagonism on all relevant inhibitory effect levels. Nonetheless, priming SK-OV-3 cells with CBD for 24h to sensitize them to the effect of cisplatin or paclitaxel treatment has shown to decrease the IC50 of the chemotherapeutic drugs. Similar results were revealed when the cells were primed with cisplatin or paclitaxel prior to be treated with CBD. The results suggest the potential benefit of sequential, rather than simultaneous, administration of CBD and chemotherapy to enhance therapy and overcome resistance. These findings, while demonstrating the potential benefit of CBD in treating ovarian cancer, call for additional caution when combining it with chemotherapeutic agents, specifically cisplatin and paclitaxel, as the effect is shown to be cell line and drug specific. Further studies are required for the validation of the results and better understanding of these interactions. en_US
dc.language.iso en en_US
dc.subject Cannabis -- Therapeutic use en_US
dc.subject Ovaries -- Cancer -- Treatment en_US
dc.subject Cisplatin en_US
dc.subject Platinum compounds -- Therapeutic use en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.title Efficacy of Cannabidiol Combination with Cisplatin or Paclitaxel against Platinum-Resistant Ovarian Cancer Cell Lines en_US
dc.type Thesis en_US
dc.term.submitted Spring en_US
dc.author.degree MS in Pharmaceutical Development And Management en_US
dc.author.school SOP en_US
dc.author.idnumber 201300485 en_US
dc.author.commembers Daher, Costantine
dc.author.commembers Taleb, Robin
dc.author.department Pharmaceutical Sciences en_US
dc.description.physdesc 1 online resource (xviii, 91 leaves): ill. (some col.) en_US
dc.author.advisor Mroueh, Mohammad
dc.author.advisor Shebaby, Wassim
dc.keywords Cannabis en_US
dc.keywords CBD en_US
dc.keywords Ovarian Cancer en_US
dc.keywords Cisplatin en_US
dc.keywords Paclitaxel en_US
dc.keywords Synergism en_US
dc.keywords Antagonism en_US
dc.keywords Sensitize en_US
dc.description.bibliographiccitations Includes bibliographical references (leaf 80-91) en_US
dc.identifier.doi https://doi.org/10.26756/th.2022.401
dc.author.email jana.ismail@lau.edu en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php en_US
dc.publisher.institution Lebanese American University en_US
dc.author.affiliation Lebanese American University en_US

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