Abstract
This study aimed to investigate the synergistic and additive anticancer effects of Cannabis sativa L. (Narlı variety) seed oil (CSSO) in combination with doxorubicin (DOX) on SH-SY5Y human neuroblastoma cells, with a particular emphasis on apoptosis.
Cell viability was evaluated using the MTT assay to determine the IC50 values of CSSO and DOX. Drug combination effects were analyzed using the SynergyFinder platform, and the most favorable synergistic combination was evaluated using reverse transcription-quantitative PCR (RT-qPCR) to assess the expression of apoptosis-related genes.
SH-SY5Y cells were treated with CSSO (1–800 µg/mL) and DOX (1–50 µg/mL) for 24 h. The IC50 values were determined to be 96.84 µg/mL for CSSO and 1.84 µg/mL for DOX, respectively. SynergyFinder analysis revealed synergistic interactions at various concentrations. Among all tested combinations, 0.92 µg/mL DOX in combination with 48.42 µg/mL CSSO showed the most favorable synergistic interaction (CI = 0.88) and was selected for further analyses. At this concentration, the corresponding ZIP synergy score was 5.1, with a 54% growth inhibition. Furthermore, this combination significantly increased the mRNA expression of Caspase-3 and Bax to 1.28 ± 0.05-fold and 1.19 ± 0.11-fold of the DOX group, respectively, corresponding to 28% and 19% increases, respectively, while reducing Bcl-2 mRNA expression to 0.68 ± 0.07-fold of the DOX group (32% reduction) (p < 0.05).
These findings suggest that CSSO may enhance the anticancer activity of DOX by inducing apoptosis, indicating its potential as an experimental adjuvant strategy for combination therapy in neuroblastoma.