Browsing by Author "Oktem, Gulperi"

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Citation - WoS: 5
Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells
(Galenos Publ House, 2020) Acikgoz, Eda; Guler, Gunnur; Oktem, Gulperi
Objective: Cancer stem cells (CSCs) are a small population in cancer, which are responsible for therapeutic resistance, relapse and metastasis. Flavopiridol has antitumor activity against various types of cancer cells. The mechanism of action of flavopiridol on CD44+/CD24- breast CSCs has not yet been fully elucidated. The aim of this study was to evaluate the mechanism of action of flavopiridol on breast CSCs (BCSC) in terms of apoptosis, cell cycle and biomolecular changes. Methods: In human breast cancer, cells with CD44+/CD24-markers were isolated from MCF-7 cell line using flow cytometry. The induction of apoptosis was investigated by Annexin-V. The effect of flavopiridol on cell cycle arrest was determined and the percent of cell populations at G0/G1, S and G2/M cycles were identified. The effect of the drug on three-dimensional cell cultures was investigated using a multicellular tumor spheroid model. In addition, the effect of flavopiridol on biomolecules has been evaluated using Fourier transform infrared (FTIR) spectroscopy, which has recently been used effectively in various scientific fields. Results: Flavopiridol especially induced early apoptosis. Cell cycle analyses revealed that flavopiridol induced cell cycle arrest in G0/G1 phase. Decreased number and diameter of spheroids was observed following flavopiridol treatment. ATR-FTIR data showed that treatment with flavopiridol led to significant changes in nucleic acids. Conclusion: According to the data obtained in this study, flavopiridol exhibits anticancer effects by altering the structure/expression level of nucleic acids and changing cell cycle progression and inducing apoptosis. These finding reveals that flavopiridol can be an effective antitumor agent for the treatment of breast cancer after in vivo and phase studies are completed.
Citation - WoS: 2
Immunohistochemical Determination of Mtor Pathway Molecules in Ovaries and Uterus in Rat Estrous Cycle Stages
(F Hernandez, 2020) Ekizceli, Gulcin; Inan, Sevinc; Oktem, Gulperi; Onur, Ece; Ozbilgin, Kemal
mTOR is a member of the PI3K/Akt/mTOR signaling pathway that participates in cell growth, proliferation, protein synthesis, transcription, angiogenesis, apoptosis and autophagy. mTOR and MAPK pahways are two important key signal pathways which are related to each other. We investigated the role of mTOR and other signaling molecules in rat ovaries and uteruses in stages of the estrous cycle. Young adult female rats were divided into four groups as proestrous, estrous, metestrous and diestrous according to vaginal smears. Immunohistochemical staining of mTORC1, IGF1, PI3K, pAKT1/2/3, ERK1 and pERK1/2 was performed and pAKT1/2/3 and ERK1 were also analyzed using western blotting on ovarian and uterine tissue samples. According to our results, PI3K/Akt/ mTOR and ERK/pERK showed an increase in the rat ovulation period. When all the groups were evaluated the immunoreactivities for all of the antibodies were detected in the oocytes, granulosa and theca cells, corpus luteum and stroma of ovary and lamina propria, surface and glandular epithelium of uterus with the strongest observed with anti-ERK1 antibody and then with a decreasing trend with anti-mTORC1, anti-pAkt1/2/3, anti-IGF1, anti-PI3K and anti-pERK1/2 antibodies in the proestrus and estrus stages. Differently from other parts of the ovary, highest antibody expression in the corpus luteum was observed in the metestrous stage. Moreover, the existence of pAKT1/2/3 and ERK1 proteins was confirmed with the Western blotting technique. We suggest that mTOR and mTOR-related ERK signaling molecules may participate in the rat ovulation process.