Kanser Biyolojisi ve Farmakolojisi Programı Makale Koleksiyonu
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Öğe Effects of exosomes on major pathways promote tumor formation and progression(Bentham Science, 2021) Köse, Mehmet Emin; Aydın, Beste; Geyik, Caner; Gönül Geyik, Öykü; Ulukaya, EnginExosomal vesicles enclose and carry a broad range of biological molecules, such as nucleic acids, lipids, and proteins, and transfer them between cells. In cancer, cells being mentioned could be neighbors in the same tumor microenvironment communicating with each other, or they could be localized at distant sites of the body, enabling suitable conditions for metastasis. Either way, it is a concrete fact that cells under physiological or pathological conditions make crosstalk via exosomal secretion. This review looks at the relation between exosomal cargo and mechanisms of cancer through recent research.Öğe Protoflavone-chalcone hybrids exhibit enhanced antitumor action through modulating redox balance, depolarizing the mitochondrial membrane, and inhibiting ATR-dependent signaling(Mdpi, 2020) Latif, Ahmed Dhahir; Jernei, Tamas; Podolski-Renic, Ana; Kuo, Ching-Ying; Vagvolgyi, Mate; Girst, Gabor; Zupko, Istvan; Develi, Elif Sedef; Ulukaya, Engin; Wang, Hui-Chun; Pesic, Milica; Csampai, Antal; Hunyadi, AttilaHybrid compounds combine fragments with complementary targets to achieve a common pharmacological goal. This approach represents an increasingly popular strategy for drug discovery. In this work, we aimed to design antitumor hybrid compounds based on an inhibitor of ataxia-telangiectasia and Rad3-related protein (ATR)-dependent signaling, protoapigenone, and a pro-oxidant ferrocene or chalcone fragment. Four new triazole-coupled hybrids were prepared. The compounds were cytotoxic against human breast cancer cell lines in vitro, showing IC(50)values in the sub-micromolar range. The nature of interactions between relevant fragments of the hybrids was evaluated by the Chou-Talalay method. Experimental combination treatment with the fragments showed additive effects or slight/moderate synergism, while strong synergism was observed when the fragments were virtually combined into their hybrids, suggesting a relevant pharmacological benefit of the coupling. All hybrids were strong inhibitors of the ATR-mediated activation of Chk1, and they interfered with the redox balance of the cells leading to mitochondrial membrane depolarization. Additionally, they induced late apoptosis and primary necrosis in MDA-MB-231 and MCF-7 breast cancer cells, respectively. Our results demonstrate that coupling the ATR-dependent signaling inhibitor protoflavone with a pro-oxidant chalcone dramatically increases the antitumor activity compared with either fragment alone. Such compounds may offer an attractive novel strategy for the treatment of various cancers.
