EXPLORING THE CYTOTOXIC AND APOPTOTIC ACTIVITIES OF PRUNUS SPINOSA ECOTYPE EXTRACT TRIGNO ON 3D AND 2D MODELS OF HUMAN CANCER CELLS

A. Di Netta¹, A. Di Pauli², R. Vona³, C. Cittadini³, S. Meschini¹, M. Condello¹ | ¹ National Center for Drug Research and Evaluation, National Institute of Health, Rome, Italy; ² Department of Anatomy, Histology, Forensic-Medicine and Orthopedics, «Sapienza» University of Rome, Rome, Italy: ³ National Center for Gender-Specific Medicine, National Institute of Health, Rome, Italy

Plant-based therapies have played a key role in cancer treatment. Among them, Prunus spinosa L. (blackthorn), rich in phenolic acids, flavonoids, and anthocyanins, has shown anticancer potential.¹ Prunus spinosa Trigno ecotype drupe extract (PsT, a plant indigenous to Molise) complexed with a nutraceutical activator complex (NAC), consisting of amino acids, vitamins and mineral salt mixtures, was patented by us in the formulation Trigno M (PsT + NAC)®.² We have shown that it is cytotoxic to several tumour cell lines but not to normal cells. Trigno M reduced the viability of colorectal cancer (CRC) HCT116 and SW480 cells, by inducing apoptosis. It inhibited colony formation compared to 5-fluorouracil (5-FU) and was effective on 3D models. Trigno M significantly delayed tumour growth in CRC xenografts without toxicity.^3,4 Furthermore, Trigno M combined with 5-FU inhibited autophagy and enhanced apoptosis in CRC spheroids, suggesting that it could improve efficacy of chemotherapy and reduce side effects.⁵ Given these promising results, we extended our study to melanoma. Trigno M reduced the viability of WM115, WM266-4, and A375 melanoma cells in a dose- and time-dependent manner, especially on metastatic WM266-4 cells. It induced irreversible morphological changes, cell cycle arrest, and apoptosis via a caspase-dependent mechanism. In conclusion, the Prunus spinosa Trigno ecotype extract could serve as an adjuvant therapy for CRC and melanoma, improving tumour responsiveness to conventional chemotherapy and modulating side effects by reducing cytotoxic drug doses.