Investigation of the Therapeutic Effects of Palbociclib Conjugated Magnetic Nanoparticles on Different Types of Breast Cancer Cell Lines

Introduction-Drug targeting and controlled drug release systems in cancer treatment have many advantages over conventional chemotherapy in terms of limiting systemic toxicity, side effects, and overcoming drug resistance.Methods and Results-In this paper, fabricating nanoscale delivery system composed of magnetic nanoparticles (MNPs) covered with poly-amidoamine (PAMAM) dendrimers and using its advantages were fully used to help the chemotherapeutic drug, Palbociclib, effectively reach tumors, specifically and stay stable in the circulation longer. In order to determine whether conjugate selectivity can be increased for the specific drug type, we have reported different strategies for loading and conjugation of Palbociclib to different generations of magnetic PAMAM dendrimers. The best method leading to the highest amount of Palbociclib conjugation was chosen, and the characterization of the Palbociclib conjugated dendrimeric magnetic nanoparticles (PALDcMNPs) were performed. In vitro pharmacological activity of the conjugation was demonstrated by measuring the cell viability and lactate dehydrogenase (LHD) release. Obtained results indicated that PAL-DcMNPs treatment of the breast cancer cell lines, leads to an increase in cell toxicity compared to free Palbociclib. The observed effects were more evident for MCF-7 cells than for MDA-MB231 and SKBR3 cells, considering that viability decreased to 30% at 2.5 lM treatment of PAL-DcMNPs at MCF-7 cells. Finally, in Palbociclib and PAL-DcMNPs treated breast cancer cells, the expression levels of some pro-apoptotic and drug resistance related genes were performed by RT-PCR analysis.Conclusion-Our knowledge indicates that the proposed approach is novel, and it can provide new insight into the development of Palbociclib targeting delivery system for cancer treatment

In vivo, in vitro and Molecular Modelling Analysis of Isoquercetin, Roseo-side, Coreximine, Anonaine, and Arianacin Molecules

Introduction: Annona muricata is a member of the Annonaceae family. This plant has a high concentration of acetogenin, which gives it excellent therapeutic property. Researchers have tested this miraculous herb in breast cancer cells treatment and observed that it could be a source of anti-cancer agents. The proposed study focused on screening the anticancer biological activity of Annona muricata plant by using the in vitro, in vivo, and in silico methods. Methods: In in vitro analysis, the IC50 was determined on two-dimensional and three-dimensional breast cancer cells. 2D cells were cultured on flat dishes typically made of plastic, while 3D cells were cultured using the hanging drop method. In in vivo analysis, Drosophila melanogaster was preferred, and the LC50 was determined. In in silico analysis, molecular docking studies have been carried out on the different classes of Annona muricata acetogenins against the target proteins. Nearly, five acetogenins were selected from the literature, and docking was performed against human Bcl-2, Bad and Akt-1 proteins. Results: In vitro and in vivo results revealed the IC50 value of 2D MDA-MB-231 cells as 330 μg.mℓ-1, of 2D MCF-7 cells as290 μg.mℓ-1, and of 3D MCF-7 and MDA-MB-231 cells about 0.005 g.mℓ-1; the LC50 value of Drosophila melanogaster was determined as 0.1 g.mℓ-1. In silico results revealed that the docked complex formed by Isoquercetin showed better binding affinity towards target proteins. Conclusion: As a result of the analysis, the Annona muricata plant has been observed to be effective against cancer and likely to be a potential drug. © 2022 Bentham Science Publishers

Anti Kanser İlaçYüklü Poli-Hidroksibütirat (PHB) Kaplı Manyetik Nanoparçacıkların Kanser Hücre Hatları Üzerindeki Etkinliğinin İmmünositokimya Yöntemi İle Belirlenmesi

Nanoparçacıklar küçük boyutları sayesinde hücre içine kolay alınabilmekte ve çeşitli malzemelerle kaplanarak yüzey özellikleri değiştirilebilmektedir. Tümör hücrelerine hedeflendirilebilen manyetik nanoparçacıklar (MNP) kanser tanı ve tedavisinde kullanılmaktadır. Manyetik özellik taşıyan nanoparçacıklar, manyetik alan varlığında istenilen bölgeye hedeflenebilme özellikleri sayesinde ilaç hedefleme ve kontrollü salıma yeni bir boyut kazandırmıştır. Bu çalışmada manyetik özellikli PHB kaplı nanoparçacıkların sentezlenmesi, anti kanser bir ilaç olan Doksorubisin’in nanoparçacıklara yüklenmesi ve in vitro koşullarda nanoparçacıkların meme kanseri hücre hatlarına uygulanması amaçlanmaktadır

DETERMINATION OF THE RELATIONSHIP BETWEEN DOXORUBICIN RESISTANCE AND WNT SIGNALING PATHWAY IN HELA AND K562 CELL LINES

WOS: 000431691800003PubMed ID: 29805346Activation of the Wnt signaling in some types of cancer and its relation with chemotherapy resistance is a very interesting issue that has been emphasized in recent years. Although, it is known that increase in the activity of beta-catenin is important in blast transformation and drug resistance, the underlying mechanisms are still unclear. In this study, changes in the expression levels of 186 genes that are thought to be important in drug resistance and Wnt signaling pathways were determined by using qPCR method in doxorubicin-sensitive and -resistant HeLa and K562 cell lines. It has been observed that the genes involved in the Wnt signaling pathways are involved in more changes in HeLa/Dox cells (36 genes) than in the K562/Dox cells (17 genes). Genes important for the development of cancer resistance have been found to be significantly different in expression levels of 18 genes in HeLa/Dox cells and 20 genes in K562/Dox cells. In both cell lines, the expression of ABCB1 gene was significantly increased to 160 and 103 fold, respectively. However, despite the resistance to same drug in HeLa and K562 cell lines, it appears that the expression levels of different oncogenes and genes involved in Wnt signaling pathways have been altered. It has been found that although resistance develops to the same drug in both cell lines, the expression levels of different genes have changed. If functional analysis of these genes is performed on patient population groups, these molecules may become candidates for novel therapeutic target molecules.TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [214S634]This work was supported by TUBITAK 3001 project (Project No: 214S634)