Browsing by Author "Soner, Burak Cem"

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Cd133+/Cd44+prostate Cancer Stem Cells Exhibit Embryo-Like Behavior Patterns
(Elsevier Gmbh, 2021) Acikgoz, Eda; Soner, Burak Cem; Ozdil, Berrin; Guven, Mustafa
Cancer stem cells (CSCs), which act as an important bridge between cancer formation and embryonic development, represent a small population associated with tumor initiation, drug resistance, metastasis and recurrence. CSCs have the ability to form spheroids in three-dimensional culture systems. Tumor spheroids derived from CSCs with symmetric and asymmetric division patterns were found to contain highly heterogeneous cell groups. The biological behavior patterns which some CSCs display serve as an important bridge between cancer formation and embryonic development. The cell population in the DU-145 prostate cancer cell line with surface markers CD133+/CD44+ was isolated by FACS. Prostate spheroids were formed by using agarose-coated plates. The morphological characteristics of the cell population within spheroid structure and the expression of Ki-67 and Caspase-3 were investigated by histochemical methods. In this study, we observed that CD133+/CD44+ prostate CSCs form different spheroid structures as well as normal spheroid structures: i) some spheroid structures formed with a highly transparent zone on the outer part of the spheroid, in addition to the normal spheroidal zones and ii) spheroidal structures obtained from prostate CD1334+/CD44+ CSCs that share the same microenvironment are hollow spheres similar to the blastula-like structure in the embryo. These spheroidal structures exhibiting embryo-like properties indicate that the expression of embryonic factors might be reiterated in CSCs. Further investigation of the formation mechanism of the transparent zone and the hollow sphere will shed light on the embryonic origin of prostate cancer and the design of new therapeutic strategies.
Enhanced G2/M Arrest, Caspase Related Apoptosis and Reduced E-Cadherin Dependent Intercellular Adhesion by Trabectedin in Prostate Cancer Stem Cells
(Public Library Science, 2015) Acikgoz, Eda; Guven, Ummu; Duzagac, Fahriye; Uslu, Ruchan; Kara, Mikail; Soner, Burak Cem; Oktem, Gulperi
Trabectedin (Yondelis, ET-743) is a marine-derived tetrahydroisoquinoline alkaloid. It is originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and currently produced synthetically. Trabectedin is active against a variety of tumor cell lines growing in culture. The present study focused on the effect of trabectedin in cell proliferation, cell cycle progression, apoptosis and spheroid formation in prostate cancer stem cells (CSCs). Cluster of differentiation (CD) 133(+high)/CD44(+high) prostate CSCs were isolated from the DU145 and PC-3 human prostate cancer cell line through flow cytometry. We studied the growth-inhibitory effects of trabectedin and its molecular mechanisms on human prostate CSCs and non-CSCs. DU-145 and PC-3 CSCs were treated with 0.1, 1, 10 and 100 nM trabectedin for 24, 48 and 72 h and the growth inhibition rates were examined using the sphere-forming assay. Annexin-V assay and immunofluorescence analyses were performed for the detection of the cell death. Concentration-dependent effects of trabectedin on the cell cycle were also evaluated. The cells were exposed to the different doses of trabectedin for 24, 48 and 72 h to evaluate the effect of trabectedin on the number and diameter of spheroids. According to the results, trabectedin induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspase-3, caspase-8, caspase-9, p53 and decrease expression of bcl-2 in dose-dependentmanner. Cell cycle analyses revealed that trabectedin induces dose-dependent G2/M-phase cell cycle arrest, particularly at high-dose treatments. Three-dimensional culture studies showed that trabectedin reduced the number and diameter of spheroids of DU145 and PC3 CSCs. Furthermore, we have found that trabectedin disrupted cell-cell interactions via E-cadherin in prostasphere of DU-145 and PC-3 CSCs. Our results showed that trabectedin inhibits cellular proliferation and accelerates apoptotic events in prostate CSCs; and may be a potential effective therapeutic agent against prostate cancer.
Expression of the Low-Density Lipoprotein Receptor (Ldlr) Gene Family in Cd133+/Cd44+ Prostate Cancer Stem Cells
(Dokuz Eylul Univ inst Health Sciences, 2023) Soner, Burak Cem; Acikgoz, Eda; Duzagac, Fahriye; Parlayan, Cuneyd
Purpose: The low-density lipoprotein receptor gene (LDLR) family plays a fundamental role in many malignancies and may have a putative cancer-boosting function. In our study, we have attempted to comparatively investigate the differential gene expressions of LDLR family in a normal prostate epithelial cell line (RWPE-1), prostate cancer cell line (DU145 cell line), prostate cancer stem cells (DU145 CSCs), and non-CSCs (DU145 non-CSCs, bulk population). Material and Methods: Cancer stem cells in the DU-145 prostate cancer cell line were isolated by flow cytometry according to CD133 and CD44 cell surface properties. Whole transcriptome sequencing data was comprehensively analyzed for each group. The protein-protein interaction network was determined using the STRING protein database. Results: Our data showed that the expression levels of Low-density lipoprotein receptor-related proteins (LRPs) such as LRP1, LRP3, LRP8 and, LRP11 were increased in the DU145 CSCs relative to the normal prostate epithelial cell line. Conclusion: Overall, our data suggest that the LRP functions and/or the expression in prostate cancer may ultimately change the invasive phenotype of the CSCs.
Neuroprotective Effect of Intrastriatal Caffeic Acid Phenethyl Ester Treatment in 6-Oh Dopamine Model of Parkinson's Disease in Rats
(Hindawi Ltd, 2021) Soner, Burak Cem; Acikgoz, Eda; Inan, Salim Yalcin; Ayla, Sule; Sahin, Ayse Saide; Oktem, Gulperi
Parkinson's disease (PD) is the second most common neurodegenerative disorder, and the main cause of PD is still not known. Until now, no cure for Parkinson's disease is yet in sight. Caffeic acid phenethyl ester (CAPE) is a polyphenolic component of the propolis, which can be derived from honeybee hive propolis. We aimed to determine the effect of intrastriatal CAPE administration as a neuroprotective agent on 6-hydroxydopamine (6-OHDA)-induced PD model. Adult male Wistar rats weighing 280-320 g were used. The PD model was induced with unilateral intrastriatal 6-OHDA injection. Treatment groups received 20 mu mol/5 mu L/4 day and 80 mu mol/5 mu L/4 day CAPE 24 h after 6-OHDA injection. Eight days after 6-OHDA application, behavioral studies (adhesive tape removal test, open-field test, cylinder test, and apomorphine-induced asymmetric rotational behavior) were performed once more to compare the effects of CAPE on behavior tests. Striatal histological verifications, immunohistochemistry, and stereological quantitation were performed. Our results for the first time showed that, besides improving the motor performance, CAPE treatment also prevents 6-OHDA-induced loss of TH-positive neurons. From our results, CAPE may be a promising clinical agent in the treatment of PD.
Optimized Method for Using Embryonic Microenvironment To Reprogram Cancer Stem Cells
(Dokuz Eylul Univ inst Health Sciences, 2023) Soner, Burak Cem; Oltulu, Fatih; Ozcinar, Emine; Taskiran, Aysegul; Demir, Aleyna; Acikgoz, Eda; Oktem, Gulperi
Purpose: The embryonic microenvironment contains many properties that have not yet been fully explored. Our aim in this study is to report an optimized and efficient method that enables investigating the effects of the secretome of pluripotent embryonic stem cells on cancer stem cells.Material and Methods: The study is performed with a chimeric model consisted of mouse blastocysts, non cancer stem cells and human prostate cancer stem cells. Ovulation induced mice were used for blastocyst collection. DU145 prostate cancer cell line was separated into non cancer and cancer stem cells using cancer stem cell biomarker expressions by fluorescent activated cell sorting. Human prostate cancer stem cells and non cancer stem cells were microinjected into 4-day blastocyst culture in vitro by intracytoplasmic sperm injection.Results: Chimeric models provide us great convenience in basic oncological studies. In this study, using a chimeric model, we were able to study the secretome of mouse embryonic stem cells and their effect on cancer stem cells. The method is efficient and yield promising result; and could be used to study the effects on other cells as well.Conclusion: The embryonic stem cell microenvironment is suggested to have a great regenerative capacity, nowadays, the center of attraction for cancer research studies. Ethical issues restrict the human embryo studies, however, mimicking the in vivo human microenvironment with 3D cell cultures or bioprinting are now possible. Finally, optimization of new methods including 3D cell cultures with human cell lines will be a great opportunity for better understanding the reprogramming notion.