Metformin-loaded lecithin nanoparticles induce colorectal cancer cytotoxicity via epigenetic modulation of noncoding RNAs
| Autor: | Ahmed A, Abd-Rabou, Ahmed M, Abdelaziz, Olfat G, Shaker, Ghada, Ayeldeen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cell Death Static Electricity Antineoplastic Agents Cadherins Metformin Epigenesis Genetic Gene Expression Regulation Neoplastic PPAR gamma Drug Liberation Inhibitory Concentration 50 MicroRNAs Cell Line Tumor Lecithins Humans Nanoparticles RNA Long Noncoding Chitinase-3-Like Protein 1 Particle Size Colorectal Neoplasms |
| Zdroj: | Molecular biology reports. 48(10) |
| ISSN: | 1573-4978 |
| Popis: | Colorectal cancer (CRC) is major aliment around the word, with a cumulative rate of mortality. Metformin (MT) was recently approved as anticancer drug against solid tumors, such as CRC. Resistance to MT therapy remains to be a challenging matter facing the development of possible anti-cancer strategy. To circumvent this problem, MT nano-encapsulation has been introduced to sensitize resistant cancer cells. The purpose of the current study is to explore the MT's aptitude encapsulated in lecithin (LC) and chitosan (CS) nanoparticles to inhibit CRC proliferation through modulations of long noncoding RNAs (lncRNAs), micro RNAs (miRNAs), and some biochemical markers.Cytotoxic screenings of the newly synthesized MT-based regimens; MT, MT-LC NPs (NP1), MT-CS NPs (NP2), and MT-LC-CS NPs (NP3) against colorectal cancerous Caco-2 and HCT116 cell lines versus normal WI-38 cells were performed. The epigenetic mechanistic effects of these proposed regimens on lncRNAs and miRNAs were investigated. Additionally, some protein levels were assessed in CRC cells upon treatments; YKL-40, PPARγ, E-cadherin (ECN), and VEGF. We resulted that NP1 recorded the highest significant cytotoxic effect on CRC cells. HCT116 cells were more sensitive to the NP1 compared to Caco-2 cells. Intriguingly, it was suggested that NP1 tackled the CRC cells through down-regulation of the H19, HOTTIP, HULC, LINC00641, miR-200, miR-92a, miR-21, YKL-40, PPARγ, and VEGF expressions, as well as up-regulation of the miR-944 and ECN expressions.We concluded that the NP1 can potentially be cytotoxic to CRC cells in-vitro by modulating noncoding RNA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink