Browsing by Author "Canpinar, Hande"

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Chemotherapeutic Resistance in Anaplastic Astrocytoma Cell Lines Treated With a Temozolomide-Lomeguatrib Combination
(Springer, 2014) Ugur, Hasan Caglar; Taspinar, Mehmet; Ilgaz, Seda; Sert, Fatma; Canpinar, Hande; Rey, Juan A.; Sunguroglu, Asuman
The treatment of anaplastic astrocytoma (AA) is controversial. New chemotherapeutic approaches are needed for AA treatment. Temozolomide (TMZ) is one of the chemotherapeutic drugs for the treatment of AA. The cytotoxic effects of TMZ can be removed by the MGMT (O(6)-methylguanine-DNA methyltransferase) enzyme. Then, chemotherapeutic resistance to TMZ occurs. MGMT inhibition by MGMT inactivators (such as lomeguatrib) is an important anticancer therapeutic approach to circumvent TMZ resistance. We aim to investigate the effect of TMZ-lomeguatrib combination on MGMT expression and TMZ sensitivity of SW1783 and GOS-3 AA cell lines. The sensitivity of SW1783 and GOS-3 cell lines to TMZ and to the combination of TMZ and lomeguatrib was determined by a cytotoxicity assay. MGMT methylation was detected by MS-PCR. MGMT and p53 expression were investigated by real-time PCR after drug treatment, and the proportion of apoptotic cells was analyzed by flow cytometry. When the combination of TMZ-lomeguatrib (50 mu M) was used in AA cell lines, IC50 values were reduced compared to only using TMZ. MGMT expression was decreased, p53 expression was increased, and the proportion of apoptotic cells was induced in both cell lines. The lomeguatrib-TMZ combination did not have any effect on the cell cycle and caused apoptosis by increasing p53 expression and decreasing MGMT expression. Our study is a pilot study investigating a new therapeutic approach for AA treatment, but further research is needed.
Exploring the Combined Anti-Cancer Effects of Sodium Butyrate and Celastrol in Glioblastoma Cell Lines: a Novel Therapeutic Approach
(Humana Press inc, 2024) Kartal, Bahar; Denizler Ebiri, Farika Nur; Gueven, Mustafa; Taspinar, Filiz; Canpinar, Hande; Cetin, Sedat; Taspinar, Mehmet
Glioblastoma, a highly aggressive and lethal brain cancer, lacks effective treatment options and has a poor prognosis. In our study, we explored the potential anti-cancer effects of sodium butyrate (SB) and celastrol (CEL) in two glioblastoma cell lines. SB, a histone deacetylase inhibitor, and CEL, derived from the tripterygium wilfordii plant, act as mTOR and proteasome inhibitors. Both can cross the blood-brain barrier, and they exhibit chemo- and radiosensitive properties in various cancer models. GB cell lines LN-405 and T98G were treated with SB and CEL. Cell viability was assessed by MTT assay and IC50 values were obtained. Gene expression of DNA repair, apoptosis, and autophagy-related genes was analyzed by RT-PCR. Cell cycle distribution was determined using flow cytometry. Viability assays using MTT assay revealed IC50 values of 26 mM and 22.7 mM for SB and 6.77 mu M, and 9.11 mu M for CEL in LN-405 and T98G cells, respectively. Furthermore, we examined the expression levels of DNA repair genes (MGMT, MLH-1, MSH-2, MSH-6), apoptosis genes (caspase-3, caspase-8, caspase-9), and an autophagy gene (ATG-6) using real-time polymerase chain reaction. Additionally, flow cytometry analysis revealed alterations in cell cycle distribution following treatment with SB, CEL and their combination. These findings indicate that SB and CEL may act through multiple mechanisms, including DNA repair inhibition, apoptosis induction, and autophagy modulation, to exert their anti-cancer effects in glioblastoma cells. This is the first study providing novel insights into the potential therapeutic effects of SB and CEL in glioblastoma.
Synthesis of Novel Imidazopyridines and Their Biological Evaluation as Potent Anticancer Agents: a Promising Candidate for Glioblastoma
(Pergamon-elsevier Science Ltd, 2018) Guclu, Dilek; Kuzu, Burak; Tozlu, Israfil; Taspinar, Filiz; Canpinar, Hande; Taspinar, Mehmet; Menges, Nurettin
Novel imidazopyridine derivatives were synthesized according to a very simple protocol and then subjected to cytotoxicity testing against LN-405 cells. Two of the compounds exhibited antiproliferative effects on LN-405 cells at 10 and 75 mu M and were selected as lead compounds for further study. Safety experiment for lead compounds on WS1 was carried out and IC50 values were calculated as 480 and 844 mu M. LN-405 cell line were incubated with the lead compounds and then tested for DNA damage by comet assay and effects on cell cycle using flow cytometry. The results of these two tests showed that both lead compounds affected the G0/G1 phase and did not allow the cells to reach the synthesis phase. The log BB (blood-brain barrier) and Caco-2 permeability of the synthesized molecules were calculated and it was shown that imidazopyridine derivatives taken orally are likely to pass through gastrointestinal membrane and the blood-brain barrier.