Exploring the Therapeutic Potential of Fe3O4@Glu-Oleuropein Nanoparticles in Targeting KRAS Pathway-Regulating lncRNAs in Colorectal Cancer Cells

Mahdavi Niyaki, Zahra; Salehzadeh, Ali; Peymani, Maryam; Zaefizadeh, Mohammad

doi:10.1007/s12011-023-03892-w

Cited by 7 publications

(2 citation statements)

References 34 publications

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“…In order to investigate the importance of KRAS in CRC, the mutation rate of this gene in CRC was examined based on TCGA data. As shown in our recent study [15], ve genes, including TTN, APC, MUC16, TP53, and KRAS, had the highest mutation rates among the genes in TCGA data. The results demonstrated that the mutation rate in the KRAS gene in CRC samples was over 40%, with the majority of mutations being of the missense type.…”

Section: The Signi Cance Of Kras Alterations In Crc: Insights From Mu...supporting

confidence: 50%

Genetic Insights and Therapeutic Potential for Colorectal cancer: Mutation Analysis of KRAS Gene and Efficacy of Oleuropein-Conjugated Iron Oxide Nanoparticles

Mehdinejad,

Peymani,

Salehzadeh

et al. 2024

Preprint

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This study aimed to address the challenges of treating advanced stages of colon cancer (CRC) by exploring potential therapeutic options. The research focused on the genetic aspects of CRC, specifically the mutation rate of the KRAS gene, along with other genes like TTN, APC, MUC16, and TP53, using the TCGA dataset. Additionally, the study investigated the efficacy of Oleuropein, a polyphenolic compound found in olives, in combating CRC by using iron oxide nanoparticles coated with glucose and conjugated with Oleuropein. The study characterized the physicochemical properties of the nanoparticles and the cytotoxic effects of the nanoparticles were evaluated on CRC and normal fibroblast cell lines, demonstrating significantly higher cytotoxicity against CRC cells compared to normal cells. Furthermore, the study analyzed gene expression changes using the GSE124627 dataset to understand the influence of KRAS alterations. It identified numerous upregulated and downregulated genes in KRAS-overexpressing samples, suggesting their involvement in critical cancer-related pathways. These findings suggest that KRAS-influenced genes could serve as potential therapeutic targets for CRC treatment. The study also examined the expression levels of identified genes in CRC samples compared to normal samples. Among the upregulated genes, 22 showed significant increases in cancer samples, while 14 downregulated genes exhibited decreased expression in both KRAS-influenced and cancer samples. Cox regression analysis identified specific upregulated genes, including ANKZF1, SNAI1, PPFIA4, SIX4, and NOTUM, associated with poor prognosis. Kaplan-Meier analysis further confirmed the correlation between increased expression of these genes and higher patient mortality rates. In conclusion, this study provided valuable insights into the genetic aspects of CRC and potential therapeutic strategies. The use of Oleuropein-conjugated iron oxide nanoparticles showed promising cytotoxic effects on colon cancer cells. These findings contribute to advancing our understanding of CRC and offer potential targets for further investigation and the development of novel therapeutic approaches.

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Section: The Signi Cance Of Kras Alterations In Crc: Insights From Mu...supporting

confidence: 50%

Genetic Insights and Therapeutic Potential for Colorectal cancer: Mutation Analysis of KRAS Gene and Efficacy of Oleuropein-Conjugated Iron Oxide Nanoparticles

Mehdinejad,

Peymani,

Salehzadeh

et al. 2024

Preprint

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“…Different approaches have been evaluated to reach this objective through the development of OLE and HT derivatives or carrier systems. For example, peracetylated OLE had a stronger anti-proliferative and antioxidant activity than OLE in thyroid and breast cancer in vitro [ 33 , 307 ]; iron oxide nanoparticles coated with glucose and conjugated with OLE showed a notable cytotoxic action against colorectal cancer cell line SW480 [ 308 ]; chitosan nanoencapsulation of HT was shown to be unaffected by time-dependent dynamic changes in efficacy observed for free HT in lung and breast cancer cell lines [ 37 ]; hydroxytyrosyl dodecyl ether, an HT alkyl ether derivative, had a very strong cytotoxic activity at low concentrations (IC50 = 19.9 ± 4.6 μM) in lung cancer cells in vitro [ 38 ]; hydroxytyrosyl oleate, an HT ester, exerted the same effects shown by HT on SH-SY5Y neuroblastoma cells at lower concentrations [ 93 ]; HT-loaded poly lactide-co-glycolide-co-polyacrylic acidnanoparticles exhibited cytotoxic and transcriptional regulating effects at lower concentrations (6 ppm) than free HT in colorectal cancer in vitro [ 77 ].…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

Gervasi,

Pojero

2024

Biomedicines

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The fact that the Mediterranean diet could represent a source of natural compounds with cancer-preventive and therapeutic activity has been the object of great interest, especially with regard to the mechanisms of action of polyphenols found in olive oil and olive leaves. Secoiridoid oleuropein (OLE) and its derivative hydroxytyrosol (3,4-dihydroxyphenylethanol, HT) have demonstrated anti-proliferative properties against a variety of tumors and hematological malignancies both in vivo and in vitro, with measurable effects on cellular redox status, metabolism, and transcriptional activity. With this review, we aim to summarize the most up-to-date information on the potential use of OLE and HT for cancer treatment, making important considerations about OLE and HT bioavailability, OLE- and HT-mediated effects on drug metabolism, and OLE and HT dual activity as both pro- and antioxidants, likely hampering their use in clinical routine. Also, we focus on the details available on the effects of nutritionally relevant concentrations of OLE and HT on cell viability, redox homeostasis, and inflammation in order to evaluate if both compounds could be considered cancer-preventive agents or new potential chemotherapy drugs whenever their only source is represented by diet.

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Genetic insights and therapeutic potential for colorectal cancer: mutation analysis of KRAS gene and efficacy of Oleuropein-conjugated iron oxide nanoparticles

Mehdinejad,

Peymani,

Salehzadeh

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Exploring the Therapeutic Potential of Fe3O4@Glu-Oleuropein Nanoparticles in Targeting KRAS Pathway-Regulating lncRNAs in Colorectal Cancer Cells

Cited by 7 publications

References 34 publications

Genetic Insights and Therapeutic Potential for Colorectal cancer: Mutation Analysis of KRAS Gene and Efficacy of Oleuropein-Conjugated Iron Oxide Nanoparticles

Genetic Insights and Therapeutic Potential for Colorectal cancer: Mutation Analysis of KRAS Gene and Efficacy of Oleuropein-Conjugated Iron Oxide Nanoparticles

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

Genetic insights and therapeutic potential for colorectal cancer: mutation analysis of KRAS gene and efficacy of Oleuropein-conjugated iron oxide nanoparticles

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