Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis

• Published in: Scientific reports Vol. 9; no. 1; p. 4986
• Main Authors: D’Abrosca, Brigida, Ciaramella, Vincenza, Graziani, Vittoria, Papaccio, Federica, Della Corte, Carminia Maria, Potenza, Nicoletta, Fiorentino, Antonio, Ciardiello, Fortunato, Morgillo, Floriana
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.03.2019; Nature Publishing Group
• Subjects: 13/2; 13/31; 140/131; 631/1647/2258/878/1263; 631/67/1612/1350; 631/92/609; 82/16; 82/29; Antitumor agents; Apoptosis; Apoptosis - drug effects; Carcinoma, Non-Small-Cell Lung - pathology; Cell culture; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Chemotherapy; CHOP protein; Cisplatin; Cisplatin - pharmacology; Cytotoxicity; DNA damage; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Humanities and Social Sciences; Humans; Lung cancer; Lung Neoplasms - pathology; Metabolites; multidisciplinary; NMR; Non-small cell lung carcinoma; Nuclear magnetic resonance; Oxylipins - pharmacology; Plant extracts; Plant Extracts - pharmacology; Proton Magnetic Resonance Spectroscopy; Rutin; Rutin - pharmacology; Science; Science (multidisciplinary); Secondary metabolites; Survival; Tumors; Urtica dioica; Urtica dioica - chemistry
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-41372-1

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the ineffectiveness of the current therapies seriously limits the survival rate of NSCLC patients. In the search for new antitumor agents, nature has played a pivotal role providing a variety of molecules, which are likely to exert selective anti-tumour properties. Herein, we investigated the antiproliferative potential of Urtica dioica L. extract (UD) against NSCLC cell models with low sensitivity to cisplatin, a cytotoxic agent largely employed to cure NSCLCs. UD inhibited cell proliferation in the selected cells, while no toxic effects were observed in normal lung cells. Furthermore, the co-treatment of UD and cisplatin notably sensitised NSCLC cells to cisplatin. Mechanistically, we discovered that UD-promoted endoplasmic reticulum (ER) stress via activation of the growth arrest and DNA damage-inducible gene 153 (GADD153) triggering apoptosis. We also performed an extensive NMR analysis of UD, identifying rutin and oxylipins as the main secondary metabolites present in the mixture. Additionally, we discovered that an oxylipins’ enriched fraction contributes to the antiproliferative activity of the plant extract. In the future, this study may provide new chemical scaffolds for the design of anti-cancer agents that target NSCLCs with low sensitivity to cisplatinum.