Abstract 4935: Cannabidiol and cannabis extract protect cells against platinum-based chemotherapy via cellular uptake

Abstract

Abstract Cannabinoids including cannabidiol belong between constituents of cannabis sp. (marijuana plant). Purified or as a part of cannabis products, the compounds are frequently used by cancer patients to attenuate chemotherapy-induced side effects such as pain, nausea, and vomiting. The presence of cannabis products on the public market expands each year while the illegality status weakens in an increasing number of countries. U.S. Food and Drug Administration has approved several cannabis-based drugs for seizures induced by Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex, also for the lost appetite of AIDS patients, and chemotherapy-induced nausea and vomiting. Oncological patients are further and strongly motivated to take the drugs in combination with chemotherapy by numerous reports demonstrating the anticancer effects of cannabinoids. Nevertheless, here we present unsettling data that cannabis extract together with CBD negatively interferes with worldwide approved platinum-based drugs cisplatin, carboplatin, and oxaliplatin. The phenomenon is proven across three cellular models including primary cells. Even low concentrations of cannabidiol or cannabis extract reduced the toxicity of platinum-based drugs using long-term colony forming assay and/or short-term crystal violet assay. Increased resistance of cells was also accompanied by decreased cellular stress as evaluated by quantitative immunofluorescence microscopy and immunoblotting. Most importantly, concomitant cannabidiol and cisplatin exposure results in the decreased presence of cisplatin-modified DNA. Following the information, we determined platinum content in cells by ICP-MS. The experiment uncovered significantly decreased intracellular platinum content indicating an effect on cellular transport. Furthermore, the mechanism is translational independent as shown by the experiment with cycloheximide. This study offers crucial information that patients and physicians should take into account regarding possible interactions between platinum-based drugs and cannabis-based products. Furthermore, the study on the contradictory effects of cannabis products in cancer treatment may be motivated by this project. Citation Format: Tereza Buchtová, Lucie Beresova, Katarina Chroma, Martin Mistrik. Cannabidiol and cannabis extract protect cells against platinum-based chemotherapy via cellular uptake. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4935.