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Apoptotic Effects of Some Tetrahydronaphthalene Derivatives on K562 Human Chronic Myelogenous Leukemia Cell Line

[ Vol. 17 , Issue. 14 ]

Author(s):

Asli Koc*, Tulin Ozkan*, Yalda Hekmatshoar, A. Selen Gurkan-Alp, Fugen Aktan, Zeliha Buyukbingol, Asuman Sunguroglu, Erdem Buyukbingol and Arzu Zeynep Karabay*   Pages 1924 - 1930 ( 7 )

Abstract:


Background: Retinoids which are vitamin A (Retinol) derivatives have been suggested to mediate the inhibition of cancer cell growth and apoptosis. It has been reported that all trans retinoic acid (ATRA) exhibited suppressive effects on different types of leukemia including chronic myelogenous leukemia.

Objective: In the present study, we aim to find out the effects of 6 synthetic N-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalene-2-yl)-carboxamide derivatives (compound 6-12) on cell viability and apoptotic pathways in K562 human chronic myelogenous leukemia cell line.

Methods: Cell viability and apoptosis were examined by spectrophotometric thiazolyl blue tetrazolium bromide (MTT) and caspase-3 assay, western blot, RT-PCR and flow cytometry.

Results: Our results indicated that compound 6 (5-(1,2-Dithiolan-3-yl)-N-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalen-2-yl)pentanamide), 8 (4-(3,4-Dimethoxyphenyl)-N-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalen-2-yl)butanamide) and 11 (E-3-(4-Hydroxy-3-methoxyphenyl)-N-(3,5,5,8,8-pentamethyl- 5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide) exhibited apoptotic effects in K562 human chronic myelogenous leukemia cell line and induced caspase 3, PARP cleavage, Bax/Bcl-2 ratio, Bad and Bim gene expressions.

Conclusion: Some retinoid derivatives tested in this study induced apoptosis of K562 cells which suggest that these compounds may serve as potential agents in the treatment of chronic myelogenous leukemia.

Keywords:

Retinoids, chronic myelogenous leukemia, apoptosis, cancer, K562, tetrahydronaphthalene.

Affiliation:

Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Department of Medical Biology, Faculty of Medicine, Ankara University, Ankara, Department of Medical Biology, Faculty of Medicine, Ankara University, Ankara, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Ankara, Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Department of Medical Biology, Faculty of Medicine, Ankara University, Ankara, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Ankara, Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara

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