Santolina pinnata Viv. Exerts Promising Antitumor Activity against Breast Cancer Cells and Anti‐Inflammatory Effects in LPS‐Stimulated RAW 264.7 Cells

Cancer is one of the largest causes of mortality in the world, and due to its incidence, the discovery of novel anticancer drugs is of great importance. Many successful anticancer drugs used in clinical practices are derived from natural products. The genus Santolina is a group of species distributed in the Mediterranean area and used in traditional medicine for their biological properties. The aim of this work was to investigate, for the first time, the multi‐target biological potential of Italian Santolina pinnata in relation to their chemical profile, by which an interesting natural source of valuable phytochemicals endowed with anticancer and anti‐inflammatory features could be assessed. n‐Hexane (EHSP) and methanol (EMSP) extracts were investigated by gas chromatography (GC) and gas chromatography‐mass spectrometry (GC‐MS) and ultra‐highperformance liquid chromatography (UHPLC), respectively. Anti‐proliferative activity was analyzed on MCF‐7 and MDA‐MB‐231 breast cancer cells, as well as on non‐tumorigenic MCF‐10A cells, by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay. Apoptotic death was assessed by comet assay. Cell motility and invasive features were examined in highly invasive MDA‐MB‐231 by wound‐healing scratches, while, in both breast cancer cell lines, by gel‐zymography experiments. The anti‐inflammatory potential was analyzed by nitric oxide (NO) production and the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) staining experiments in bacterial lipopolysaccharides (LPS) which stimulated RAW 264.7 cells. EHSP and EMSP extracts exhibited anticancer activity against breast cancer cells, promoting apoptotic death, as well as decreasing cell migration and invasive behaviours. The highest activity (IC50 of 15.91 μg/mL) was detected against MDA‐MB‐231 cells, a highly invasive breast cancer cell line. Both extracts were also able to promote anti‐inflammatory effects (IC50 values ranging from 27.5 to 61.14 μg/mL), as well as to reduce NO levels by inducing inhibitory effects on NF‐κB nuclear translocation in LPS‐stimulated RAW 264.7 cells. The different biological behaviours found between the extracts could be related to their different chemical compositions. Herein, the multi‐target biological potential of S. pinnata in inducing antitumor and anti‐inflammatory effects was comprehensively demonstrated. These findings will provide important stepping‐stones for further investigations and may lead to the development of highly effective S. pinnata extract‐based treatments for breast cancer and inflammatory processes.