Cytotoxic and anticancer activity of Berberis heteropoda Schrenk and Juniperus communis L. in normal and cancer cells: mechanisms of action and selectivity

Brazilian Journal of Biology, 2026

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DOI 10.1590/1519-6984.309448
Data confidence 70 medium
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Abstract

Abstract Cancer is a major cause of morbidity and mortality worldwide, while the effectiveness of existing treatments remains limited by systemic toxicity, incomplete selectivity, therapeutic resistance, and disease recurrence. Plant-derived natural products provide chemically diverse compounds with potential activity against multiple cancer-related processes; however, preclinical cytotoxicity should be distinguished from demonstrated therapeutic efficacy. This structured integrative review critically compared the phytochemical composition, cytotoxic activity, molecular mechanisms, selectivity, pharmacokinetic properties, safety, and translational potential of Berberis heteropoda Schrenk and Juniperus communis L. Evidence was classified according to botanical provenance, preparation type, experimental model, and level of mechanistic validation. B. heteropoda contains diverse isoquinoline alkaloids and phenolic constituents, but direct species-specific evidence from malignant and nonmalignant cell models remains insufficient. Anticancer mechanisms attributed to berberine and related protoberberine alkaloids therefore represent indirect evidence and cannot be generalized to B. heteropoda without experimental confirmation. In comparison, several J. communis extracts and essential oils have demonstrated effects on cell viability, cell-cycle progression, apoptosis, p53 and PI3K/Akt signalling, angiogenesis-related pathways, and invasion-associated proteins. Nevertheless, differences in botanical origin, chemical standardization, experimental design, and selection of nonmalignant comparators limit reproducibility and interpretation of selectivity. Neither species currently has sufficient pharmacokinetic, toxicological, or clinical evidence to support established use as an anticancer therapy. Future research should prioritize authenticated plant material, reproducible chemical characterization, paired malignant and tissue-relevant nonmalignant models, mechanism-specific validation, and in vivo assessment of exposure, safety, and antitumor efficacy.