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Öğe Antitumor activities on HL-60 human leukemia cell line, molecular docking, and quantum-chemical calculations of some sulfonamide-benzoxazoles(Taylor & Francis Ltd, 2017) Öksüzoğlu, Emine; Ertan Bolelli, Tuğba; Can, Hatice; Tarhan, Mehtap; Özturk, Kamile; Yıldız, İlkayWe previously synthesized some novel benzoxazole derivatives-containing sulfonamide. In this study, the compounds were investigated for their antitumor activities against the HL-60 human leukemia cells, using the MTT assay. Moreover, quantum chemical calculations using the DFT methods were applied for understanding the difference in antitumor activity. Additionally, molecular docking into active site of the DNA Topo II enzyme was performed on 3QX3. PDB file in order to find out possible mechanism of antitumor effect. According to all obtained results showed that compounds 1b, 1c, and 1d could be potential drug candidates as new antitumor agents, and are promising for cancer therapy.Öğe Antitumor and apoptotic effects of new-generation platinum compounds on human leukemia cell lines HL-60 and K562(Springer, 2022) Karacaer, Neslihan Tekin; Kerimoğlu, Barış; Baran, Talat; Tarhan, Mehtap; Menteş, Ayfer; Öztürk, KamileThe goal of this investigation is to report the fabrication, characterization, cytotoxicity, and apoptotic assessment of new platinum based compounds on K562 and HL-60 human leukemia cells. Two new platinum (II) compounds, Pt-5a and Pt-6a, were prepared and characterized by fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy ((HNMR)-H-1), environmental scanning electron microscopy (ESEM) and energy dispersive spectrometer (EDS) techniques. The cytotoxic activities of the compounds were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test. Caspase-3, B-cell lymphoma 2 (Bcl-2), and B-cell lymphoma 2 associated X protein (Bax) gene expressions were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) to illuminate the mechanism of apoptosis. The results present that the applied compounds exhibited dose-dependent cytotoxic effects in-vitro. Pt-5a and Pt-6a compounds caused a rise in Bax in HL-60 cells while a reduction in Bcl-2 was recorded in all applied doses. In HL-60 cells, an increase in caspase-3 was detected at doses of 25 mu M and 50 mu M of Pt-5a and 30 mu M of Pt-6a. The treatment with 40 mu M of Pt-5a increased caspase-3 and Bax in K562 cells compared with control cells. Bcl-2 was found to be low in 20 mu M of Pt-5a treatment in K562 cells. Pt-6a caused a significant increase in caspase-3 at the dose of 30 mu M in the same cells. It is proposed that the newly synthesized platinum compounds may prove to be significant in the development of anticancer-effective drugs as they trigger apoptosis in a dose-dependent manner.Öğe Cytotoxic and apoptotic activities of novel Pd(II) complexes against human leukemia cell lines in vitro(Taylor & Francis, 2017) Tekin, Neslihan; Öztürk, Kamile; Baran, Talat; Kerimoğlu, Barış; Tarhan, Mehtap; Menteş, AyferIn the investigation for alternative chemotherapeutic strategies against leukemia, Pd(II) complexes were synthesized and investigated for cytotoxic and apoptotic properties on two human leukemia cell lines (HL-60 and K562). Pd(II) complexes (Pd-5a and Pd-6a) with 5a and 6a as ligands were synthesized and characterized by H-1-NMR and F-TIR. The cytotoxicity of the compounds was quantified using MTT method. Bax, Bcl-2, and caspase 3 gene expression levels were estimated using RT-qPCR. Here we show that Pd(II) complexes have important cytotoxic activity on human leukemia cell lines. RT-qPCR indicated that Bax and caspase 3 gene expression levels were increased after 24h treatment with Pd-5a and Pd-6a complexes in both HL-60 and K562 cells at some selected dose. Furthermore, Bcl-2 gene expression level decreased after 24h treatment with Pd-5a and Pd-6a complexes in K562 cells at all selected dose. In HL-60 cells, only one selected Pd-5a dose (25 mu M) decreased the gene expression level of Bcl-2. The results obtained in the present investigation indicate that these two newly synthesized Pd(II) complexes have apoptotic effects at appropriate doses through caspase 3 and Bax genes and might represent a novel potentially active agents for the management of human leukemia cell lines.Öğe Investigation of the possible effect of s-allyl-l-cysteine on apoptosis and autophagy in human leukemia cell line(Afyonkarahisar Sağlık Bilimleri Üniversitesi, 2021) Tekin Karacaer, Neslihan; Kerimoğlu, Barış; Tarhan, Mehtap; Öztürk, KamileS-Allyl-L-cysteine (SAC) is a biological active organosulfur component of garlic and has various pharmacological effects. SAC has displayed anti-cancer activity but the mechanism is unresolved. This study has focused on investigating the possible apoptotic and autophagic effects of SAC on two human leukemia cell lines: acute promyelocytic leukemia (HL-60) and chronic myeloid leukemia (K562).MATERIAL AND METHODS: Cell cytotoxicity was evaluated via MTT test. Bax, Bcl-2, caspase 3, mTOR, AKT, and PI3K gene expression amounts were identified via Real time quantitative reverse transcription polymerase chain reaction (qRT-PCR). HL-60 and K562 cells were incubated with SAC at three diverse doses (5 mM, 10 mM, and 20 mM) (3,75 mM, 7,5 mM, and 15 mM), respectively.RESULTS: SAC caused a cytotoxic effect on HL-60 and K562 cells with IC50 values of approximately 11.525 mM and 10.025 mM, respectively. In HL-60 cells, an increase in Bax expression levels was detected at doses of 5 mM and 10 mM SAC (p=0.027, p=0.000). Treatment with 10 mM SAC increased the expression level of caspase 3 in HL-60 cells as compared with the control and 5 mM SAC treated cells (p=0.000, p=0.020). In K562 cells, SAC induced a significant decrease in mTOR, AKT, and PI3K expression levels in at all doses (p=0.000, p=0.000, p=0.000).CONCLUSIONS: In conclusion, our data indicates that SAC induces autophagy in K562 cells by downregulating the PI3K/AKT/mTOR signaling pathway. Furthermore, increased Bax and caspase 3 gene expression levels suggest that SAC may be an effective active ingredient with which to induce apoptosis in HL-60 cells.Öğe Multiple Myeloma'da bortezomibe karşı gelişen direnç mekanizmasında toll like reseptörlerin rolünün araştırılması(Aksaray Üniversitesi Fen Bilimleri Enstitüsü, 2017) Tarhan, Mehtap; Öztürk, KamileMultiple myeloma (MM) kemik iliğindeki plazma hücrelerinin anormal proliferasyonu ve invazyonu ile karakterize edilen, tedavi edilemeyen hematolojik bir kanserdir. Günümüzde MM tedavisi için kullanılan en etkin tedavi yöntemlerinden birisi proteazom inhibitörü bortezomibin yer aldığı kemoterapötik rejimlerdir. Ancak bortezomibe karşı gelişen direnç mekanizması tedavinin başarısızlığına neden olmaktadır. Literatürde dirençlilik mekanizmasında rol aldığı bilinen birçok mekanizma çalışılmasına karşın, TLR'in ilaç dirençlilik mekanizmasındaki rolleri henüz aydınlatılmamıştır. Bu nedenle, bu tez çalışması ile MM hücre hatlarında bortezomibe karşı gelişen direnç mekanizmasında TLR'lerin rolünün araştırılması amaçlanmıştır. Bu amaç için, bortezomibe dirençli (KMS-20) ve hassas (KMS-28BM) MM hücre hatları kullanılmıştır. İlk olarak, bortezomibin doza ve zamana bağlı hücre canlılığına etkisi, MTT testi kullanılarak saptanmıştır. İkinci olarak, hücre hatları farklı bortezomib konsantrasyonları ile 12, 24 ve 48 saat muamele edildikten sonra total RNA izolasyonu ve ardından cDNA sentezi yapılmıştır. TLR 2, 3, 4, 7, 9 ve MyD88 genlerinin mRNA düzeyleri her gene özgü primer ve TaqMan problar kullanılarak real time RT-PCR yöntemi ile saptanmıştır. KMS-20 hücre hattında bortezomibin 12, 24 ve 48 saat için IC50 dozları sırasıyla 31.62nM; 15.85nM; 5.89nM olarak ve KMS-28BM hücre hattında ise 12, 24 ve 48 saat için IC50 dozları sırasıyla 11.84nM; 5.30nM; 3.66nM olarak saptanmıştır. KMS-20 için 12, 24 ve 48 saatlik dirençlik indeksleri (RI) sırasıyla 2.67; 2.99 ve 1.61 olarak hesaplanmıştır. Gen ifade düzeylerine bakıldığında, TLR2 ifade düzeyinin dirençli hücrede hassas hücreye göre doz ve zaman bağlı olarak çok anlamlı azalış gösterdiği bulunmuştur. TLR3 ve TLR4 gen ifadesi hassas hücrede doz ve zamana bağlı azalış gösterirken, dirençli hücrelerde tamamen baskılanmıştır. TLR7 ifadesi hassas hücrede doza ve zaman bağlı azalış gösterirken, dirençli hücrede anlamlı bir artışa neden olmuştur. TLR9 hassas hücrede doz ve zamana bağlı anlamlı azalış gösterirken, dirençli hücrede sadece yüksek konsantrasyonlarda anlamlı azalma göstermiştir. MyD88 dirençli hücrede sadece 48 saatte anlamlı artış, hassasta özellikle 24 ve 48 saatte doza ve zamana bağlı azalma göstermiştir. Sonuçta, dirençli ve hassas hücrelerdeki tüm gen ifade düzeyleri karşılaştırıldığında, dirençli hücrelerde TLR2, TLR3 ve TLR4 mRNA düzeylerindeki azalmanın ya da tamamen baskılanmanın, buna karşın TLR7 ve MyD88 mRNA düzeylerindeki artışın bortezomibe karşı gelişen direnç mekanizmasında rol alabileceği görülmüştür.
