A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer

• Published in: Pharmacological research 2018-03, Vol.129, p.500-514
• Main Authors: Cevatemre, Buse, Erkısa, Merve, Aztopal, Nazlihan, Karakas, Didem, Alper, Pınar, Tsimplouli, Chrisiida, Sereti, Evangelia, Dimas, Konstantinos, Armutak, Elif I. Ikitimur, Gurevin, Ebru Gurel, Uvez, Ayca, Mori, Mattia, Berardozzi, Simone, Ingallina, Cinzia, D’Acquarica, Ilaria, Botta, Bruno, Ozpolat, Bulent, Ulukaya, Engin
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Autophagy - drug effects; Biological Products - pharmacology; Biological Products - therapeutic use; Cell Line, Tumor; Cytoplasmic vacuolation; Endoplasmic reticulum stress; Humans; Mammary Neoplasms, Experimental - drug therapy; Mammosphere; Mice; Neoplastic Stem Cells - drug effects; Triterpenes - pharmacology; Triterpenes - therapeutic use; Triterpenoid; Xenograft Model Antitumor Assays
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2017.11.027

[Display omitted] •Dynamics and control of reactive distillation using an extraneous entrainer for the production of n-butyl acetate are studied.•Different multiplicities are found to appear depending on whether the azeotrope that forms with water is binary or ternary.•Different control schemes depending on the type of azeotrope are proposed. Several natural products have been suggested as effective agents for the treatment of cancer. Given the important role of CSCs (Cancer Stem Cells) in cancer, which is a trendy hypothesis, it is worth investigating the effects of pristimerin on CSCs as well as on the other malignant cells (MCF-7 and MDA-MB-231) of breast cancer. The anti-growth activity of pristimerin against MCF-7 and MCF-7s (cancer stem cell enriched population) cells was investigated by real time viability monitorization (xCELLigence System®) and ATP assay, respectively. Mode of cell death was evaluated using electron and fluorescence microscopies, western blotting (autophagy, apoptosis and ER-stress related markers) and flow cytometry (annexin-V staining, caspase 3/7 activity, BCL-2 and PI3K expressions). Pristimerin showed an anti-growth effect on cancer cells and cancer stem cells with IC50 values ranging at 0.38–1.75μM. It inhibited sphere formation at relatively lower doses (