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

Erica spiculifolia Salisb. (Balkan heath) is an evergreen shrub growing in the mountain shrublands of Eastern Europe. E. spiculifolia 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 E. spiculifolia 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 E. spiculifolia 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 E. spiculifolia antitumor activity, indicating its potential as a natural alternative for future therapeutic applications.