GREEN ONCOLOGY: USO DELLA NORTOPSENTINA COME ADIUVANTE PER LA CURA DEL TUMORE ALLA MAMMELLA

Cancer is a leading cause of death worldwide and breast cancer is the most frequently diagnosed tumor in women, accounting for about 30% of new diagnoses. Despite improvements in early diagnosis and progress in the treatment of localized breast cancer, the mortality rate of patients remains high, with 25% of breast cancer patients experiencing relapse within 10 years. Overwhelming evidence has shown that cancer stem cells (CSCs), a small subpopulation of cancer cells highly resistant to treatments, are responsible for tumor progression and the occurrence of relapses. In light of these features, CSCs represent a highly valuable target for the development of innovative and effective therapeutic strategies aimed at the eradication of breast cancer. Over the last decades plant- and marine-derived natural products have demonstrated significant therapeutic potential in modern oncology. In fact, the development of alternative methods using natural raw materials, within the framework of "Green Oncology" promoted by the European Union, represents a promising and cost-effective anti-cancer strategy with minimal side effects. Here, we investigated the effect of 2,4-bis-3-indolyl (Norto), an analogous compound of the alkaloid Nortoseptin, and humic natural products derived from organic decomposition of artichoke and olive. While Norto inhibited the proliferation of stabilized breast cancer cells by inducing a dormancy-like phenotype, humic substances (HS), in addition to their antimicrobial and antioxidant properties, displayed strong anti-cancer potential. HS induced apoptosis and DNA damage in cancer cells, both alone and in combination with standard chemotherapy. Further studies are needed to unravel the molecular mechanisms regulated by natural products, validate their antitumor potential, and explore their role in combinatorial therapies. By increasing tumor sensitivity to chemotherapy, natural products hold promise for enhancing current treatment regimen efficacy and accelerating their translation into clinical practice.