Synthesis of Nano-Paramagnetic Oleuropein to Induce KRAS Over-Expression: A New Mechanism to Inhibit AGS Cancer Cells

• Published in: Medicina (Kaunas, Lithuania) Vol. 55; no. 7; p. 388
• Main Authors: Barzegar, Farhad, Zaefizadeh, Mohammad, Yari, Reza, Salehzadeh, Ali
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 19.07.2019; MDPI AG
• Subjects: Adenocarcinoma - prevention & control; AGS Cancer; Cell Proliferation - drug effects; Gene Expression - drug effects; Humans; Iridoids - pharmacology; Iridoids - therapeutic use; K-Ras; miR-200 oncogene; nano-oleuropein; Nanoparticles - therapeutic use; Olea - enzymology; Olea - genetics; oleuropein; Proto-Oncogene Proteins p21(ras) - biosynthesis; Proto-Oncogene Proteins p21(ras) - blood; real-time PCR; Spectrometry, X-Ray Emission - methods; Stomach Neoplasms - prevention & control; miR-200 oncogene; nano-oleuropein; AGS Cancer; oleuropein; real-time PCR; K-Ras
• DOI: 10.3390/medicina55070388
• ISSN: 1648-9144; 1010-660X

Human gastric adenocarcinoma (AGS) is one of the most common malignant cancers worldwide. The present study aimed to transfer oleuropein into cancer cells using synthetic paramagnetic nanoparticles and study their effect on the AGS (ATCC CRL1739™) cell line. Paramagnetic nano-oleuropein was synthesized using four-stage co-precipitation by developing NH-connected bridges and was evaluated by EDS, SEM and FTIR methods. Different concentrations of magnetic oleuropein (0, 0.15, 0.45, 1.37, 4.12, 12.35, 37.04, 111.11, 333.33, 1000 µg/mL) were used to treat the AGS cell line in a completely randomized design using a statistical framework with three replicates. The relative expression rate of miR-200 and KRAS oncogenes was evaluated using real-time PCR. The inhibition rate of the AGS cells was assessed using the MTT test at 24, 48 and 72 h intervals. The results showed that there was a significant difference between the inhibition rates of magnetic nano-oleuropein at IC50-24h (23.6 µg/mL), IC50-48h (15.2 µg/mL) and IC50-72h (9.2 µg/mL). Real-time PCR indicated that the relative expression of KRAS and miR-200 genes was highest at IC50 at these intervals. Magnetic nano-oleuropein can be subjected to objective testing and clinical evaluations as a natural antioxidant to prevent and treat gastric adenocarcinoma.