Metabolite Profiling of Bioactive Compounds in Algerian <i>Opuntia</i> Fruits With Emphasis on Their Anticancer Properties

Opuntia plants are well-known for their richness in numerous compounds with potential biological properties against human diseases, including ulcers, asthma, and hemorrhoids. This study aimed to evaluate the anticancer activity of different parts (seeds, pulp, and fruit) and extraction solvents of both cultivated and wild Opuntia fruits against various cell lines, as well as to identify the potential components responsible for this activity using a bioactivity-based molecular networking approach with LC-MS/MS data. Among the different Opuntia extracts, the aqueous wild seeds (WS) exhibited a potent cytotoxic effect (>35% of cytotoxicity) against the carcinogenic HCT-116, MG-63, and T-47D cells with minor toxicity (<15%) to immortalized non-cancerogenic normal cells (hCMEC/D3, HaCaT, and 3T3-L1). A notable sensibility of the colon carcinoma cancer line (HCT-116) was observed toward the aqueous WS, reducing their viability by 65.5% at the concentration of 1000 µg/mL, with an IC₅₀ of 685.4 ± 24.3 µg/mL. This extract also displayed cytotoxic effects on HCT-116 multicellular spheroids, impacting only the outer layer of the spheroids containing the active proliferating cells. The metabolite profiling by LC-MS/MS on the GNPS platform identified 79 mass peaks; among them, 18 were specific to the aqueous WS, which could be related to the observed cytotoxic activity. Among them, some compounds were already reported to have anticancer properties, namely, americanin, xanthoxylol, syringaldehyde, vanillin, and sinapaldehyde. To conclude, Opuntia seeds may constitute an attractive source of several promising anticancer agents, paving the way for potential pharmacological exploitation to treat colon carcinoma.