The Determination of Molecular and Toxicological Mechanisms of Cucurbitacine E in Model Organism Drosophila melanogaster and Various Cancer Cell Lines: Molecular modelling, docking and dynamic simulation studies
Yazarlar (3)
Aydin Tuncbilek
Erciyes Üniversitesi, Türkiye
Prof. Dr. Serap YALÇIN AZARKAN
Kırşehir Ahi Evran Üniversitesi, Türkiye
Prof. Dr. Fahriye ERCAN
Kırşehir Ahi Evran Üniversitesi, Türkiye
| Makale Türü | Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale) | ||
| Dergi Adı | Current Computer Aided Drug Design (Q3) | ||
| Dergi ISSN | 1573-4099 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | Türkçe | Basım Tarihi | 01-2023 |
| Cilt / Sayı / Sayfa | 19 / 2 / 81–93 | DOI | 10.2174/1573409919666221031112223 |
| Makale Linki | http://dx.doi.org/10.2174/1573409919666221031112223 | ||
| Özet |
| Introduction: Cucurbitacins are one of the most important components of Ecballium elaterium. Among the cucurbitacins, Cucurbitacin E was the first to be isolated. This study fo-cused on screening the anticancer and insecticidal potential of Cucurbitacin E by the in-vitro, in-vivo, and in-silico methods. Methods: In the study, toxicity analysis of Cucurbitacin E was determined on HeLa, Caco 2 cancer cell lines and D. melanogaster. While the expression levels of the BAD, BCL-2, AKT-1 and H-purine genes of cancer cell lines were determined, the CG15530, BUFFY, AKT-1 and Purine genes of D. melanogaster were determined by RT-PCR. Besides, molecular docking and dynamic properties of Cucurbitacin E with human and insectoid enzymes were presented in silico. Results: The IC50 value of Cucurbitacin E in the HeLa ovarian and Caco 2 colon cancer cell lines was determined to be 42 ug/ml and 85 ug/ml, respectively. The LC50 and LC99 doses for fruit flies were determined to be 47,693 µg/ml and 133,251 µg/ml, respectively. Gene expression analysis revealed that Cucurbitacin E showed the greatest effect on Purine and AKT-1 genes in D. melano-gaster. We analyzed all genes by Western blot but did not detect significant changes in genes oth-er than H-purine. In silico studies revealed that the Purine protein of D. melanogaster had the highest bonding energy with Cucurbitacin E as a ligand. Similarly, Cucurbitacin E showed great affinity towards H-purine (-10.2 kcal/mol). Molecular dynamics simulation studies were also performed to determine the stability of the dynamic process. Conclusion: As a result of our in vivo, in vitro and bioinformatic analyzes, it has been seen that Cucurbitacin E is effective against the cancer types and model insects studied. |
| Anahtar Kelimeler |
| cancer | Cucurbitacin E | Drosophila melanogaster | molecular docking | molecular dynamic analyses | toxicity |
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| Atıf Sayıları |