Investigating the anti-cancer potential of natural bioactive molecules in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is the most common diagnosed malignancies in women, characterized by aggressiveness (Afifi N, et al, 2023). Current treatments, consisting of radiation, chemotherapy, immunotherapy and surgery, drastically impact on the patient’s life quality and are still associated with a high risk of drug-resistance and relapse (Obidiro O, et al, 2023). Recently, it was demonstrated that natural extracts could represent a promising therapeutic strategy with reduced side effects, either as standalone anti-cancer treatment or in combination with the conventional therapies (Newman, et al, 2020). In this contexts, National Biodiversity Future Center aims to isolate Italian flora derived bioactive molecules and characterize their potential therapeutical properties. Thus, MDA-MB-231 cells, a triple negative human epithelial cancer cell line, as well as MCF10A, human epithelial normal cells line, were stimulated for 24h and 48h with Petasites Paradoxus, Salvia Pratensis, Succisa Pratensis and Typha Iaxmannii. Importantly, Salvia p. and Succisa p. did not affect MCF-10A cells number, while MDA-MB-231 proliferation was significantly reduced by 40% after 24h of treatment. To investigate the underlying molecular mechanisms, we analyzed the expressions of key molecules involved in intrinsic and extrinsic apoptotic pathways, in the inflammasome, and in oxidative stress. Specifically, we demonstrated that TGFβ, a key molecule driving metastasis and resistance in TNBC, was drastically reduced after 24h of treatment with Salvia p. and Succisa p. compared to unstimulated condition. These findings suggest TGFβ as a potential regulator of Salvia and Succisa extract-mediated effects, highlighting the potential for further studies on natural bioactive molecules to pave the way for the development of novel and promising therapies.