Insight into Cytotoxic Potential of Erica spiculifolia Salisb (Balkan Heath)

<i>Erica spiculifolia</i> Salisb. (Balkan heath) is an evergreen shrub growing in the mountain shrublands of Eastern Europe. <i>E. spiculifolia</i> was used as a diuretic, anti-inflammatory, and antioxidant herbal remedy. The present study aims to conduct an evaluation of the phytochemical composition and antitumor activity of the methanol-aqueous extract from <i>E. spiculifolia</i> aerial parts to explore its potential in cancer treatment. Overall, a total of 54 secondary metabolites, including 28 hydroxybenzoic, hydroxycinnamic acids, and phenolic glycosides, and 10 triterpene acids, together with 17 flavonoids, were identified or annotated in the assayed <i>E. spiculifolia</i> extract using liquid chromatography-high-resolution mass spectrometry. The cytotoxic activity of the extract, alongside gallic, protocatechuic, and oleanolic acids as its constituents, was screened against a panel of malignant human cell lines of different origin (LAMA-84, HL-60, MDA-MB-231, MCF-7, and CASKI). The most prominent antiproliferative effect of the studied extract (with IC₅₀ 16.6 μg/mL), matched with the highest tumor selectivity (SI > 120), was observed in the LAMA-84 myeloid cells. These findings were further supported by gallic and oleanolic acid (IC₅₀ 6.2 and 1.7 μg/mL, respectively), accounting for a more distinct cytotoxicity. The strongest selective antineoplastic activity was achieved towards the triple-negative breast carcinoma cell line MDA-MB-231, with an IC₅₀ of 32.5 μg/mL. This study provided compelling evidence for a wide spectrum of <i>E. spiculifolia</i> antitumor activity, indicating its potential as a natural alternative for future therapeutic applications.