Integration of transcriptome and metabolome provides insights into metabolites and pathways associated with antiproliferative activity of cannabis flower extracts

Cannabis sativa L. has attracted increasing attention for its potential therapeutic applications, including antiproliferative properties. In this study, we investigated the bioactivity of female flower extracts from eight cannabis varieties. The results showed significant variation in antiproliferative efficacy against three cancer cell lines (AGS, HCT116, and A549), antioxidant capacity, and total phenolic content. Two varieties, ‘Galaxy CBD’ and ‘Mexican Sativa’, were selected for widely targeted metabolomics analysis due to their contrasting antiproliferative activity. Metabolomic analysis revealed distinct compositions of non-volatile and volatile metabolites between the two varieties, with 'Galaxy CBD' showing heightened levels of specific compounds associated with antiproliferative activity. Transcriptome analysis uncovered differential gene expression patterns across five stages of flower development, highlighting the genetic underpinnings of metabolic diversity. Integrating transcriptomic and metabolomic data revealed ‘Galaxy CBD’ exhibited higher expression of genes in pathways related to cannabinoid, terpenoid, and flavonoid biosynthesis, which may explain its superior antiproliferative activity. These findings provide valuable insights into the relationship between cannabis metabolite profiles, gene expression patterns and their potential medicinal properties, shedding light on the complex mechanisms underlying the antiproliferative properties of cannabis flower extracts. • First LC-MS, GC-MS based widely targeted metabolomic study on cannabis female flower extract. • Distinct metabolite profiles in varieties with contrasting antiproliferative activity. • Transcriptome and metabolome integration links heightened metabolites to pathways. • This work reveals the pathways underlying the anti-cancer properties of cannabis flower extracts.