The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines

LALE, Mustafa; SAYGUN, Oral; URAL, Ali Uğur; kosargelir, mehmet; BOYUNAĞA, Hakan; KENAR, LEVENT; KELEŞ, HATİCE; DİKMEN, Z. Günnur

The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines

Hakan BOYUNAĞA, (Kirikkale University, Faculty of Medicine, Departments of Biochemistry, Medicine, Kirikkale)

Z. Günnur DİKMEN, (Hacettepe University, Faculty of Medicine, Department of Biochemistry, Ankara)

Levent KENAR, (Gulhane Military Medical School, Departments of Biochemistry, Ankara)

Oral SAYGUN, (Kirikkale University, Faculty of Medicine, Departments of Surgery, Medicine, Kirikkale)

Hatice KELEŞ, (Kirikkale University, Faculty of Medicine, Departments of Internal, Medicine, Kirikkale)

Ali Uğur URAL, (Gulhane Military Medical School, Departments of Hematology, Ankara)

Mustafa LALE, (Advisor to the Secretary General TOBB The Union of Chambers and Commodity Exchanges of Turkey)

Mehmet KOŞARGELİR (Haydarpaşa Numune Training and Research Hospital, İstanbul)

Türk Biyokimya Dergisi

3 1

Yıl: 2013 Cilt: 38 Sayı: 1 Sayfa Aralığı: 31 - 36 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines

Öz:

Amaç: Kanser hücrelerinde metabolik yönelim, ortamın oksijen içeriği ve substrat konsantrasyonuna göre düzenlenmektedir. Kanser hücresinin enerji metabolizmasının düzenlenmesine yönelik çeşitli terapotik ajanlar halen kullanılmaktadır. Sitozin arabinosid (Ara-C) akut myeloid lösemi (AML) tedavisinde kullanılan bir pirimidin analogudur, simvastatin ise HMG-Co A (3-hidroksi-3-metil-glutaril-KoA) redüktaz inhibitörü olup kolesterol biyosentezini regüle etmektedir. Bu çalışmada, HL-60 promyelositik lösemi hücreleri ile sağlıklı beyaz kan hücrelerinin enerji metabolizmalarını belirlemek, ayrıca simvastatin ile Ara-C'nin tek tek ve kombine kullanımlarının hücrelerin enerji metabolizması üzerindeki etkilerini incelemek amaçlandı. Gereç ve Yöntemler: Bu amaçla, ilaç kullanılan ve kullanılmayan tüm HL-60 akut promyelositik lösemi hücre hatları, radyoaktif glukoz ile 4 saat inkübasyona bırakıldı. İnkübasyon sonrası, karbonhidrat katabolizmasının son ürünlerinden laktat ve hücreler tarafından üretilen radyoaktif işaretli CO2 toplanarak likit sintilasyon cihazında ölçüldü. Ayrıca her bir grupta saatteki glikojen tüketimi hesaplandı. Bulgular ve Tartışma: Çalışmanın sonucunda enerji eldesinde HL-60 promyelositik hücrelerinin anaerobik glikolizi, sağlıklı lökositlerin ise aerobik glikolizi kullandıkları saptandı. Ara-C ile Simvastatinin kombine kullanımı sonucu, HL-60 promyelositik hücrelerinde aerobik glikoliz oranlarınının belirgin şekilde arttığı ve bu hücrelerin metabolizmalarını köken aldıkları beyaz kan hücrelerininkine benzer hale geldiği sonucuna varıldı. Key words: Warburg etkisi, HL-60, enerji metabolizması, simvastatin, Ara-C.Çıkar Çatışması: Yazarlar arasında çıkar çatışması bulunmamaktadır

Anahtar Kelime:

Konular: Biyokimya ve Moleküler Biyoloji

HL-60 lösemi hücrelerinde Ara-C ve Simvastatinin tek tek ve kombine kullanımlarının enerji metabolizması üzerindeki etkileri

Öz:

Objective: Cancer cells choose their metabolic pathway depending on the oxygen content and substrate concentration of the medium. A wide spectrum of therapeutic agents regulating the energy metabolism of cancer cells are in still in use. Cytosine arabinoside (Ara-C) is a pyrimidine analogue used in the treatment of acute myeloid leukemia (AML) and simvastatin is an inhibitor of HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase, which regulates cholesterol biosynthesis. Thus, this study aimed to assess the energy metabolism of HL-60 promyelocytic leukemia cells and healthy white blood cells, additionally to determine the effects of simvastatin and Ara-C, alone or in combination on the energy metabolism of these cells. Materials and Methods: Healthy white blood cells, untreated and treated HL-60 promyolocytic leukemia cell lines were incubated for 4 hours with radiolabelled glucose. Following incubation, lactate, which is one of the end products of the carbohydrate catabolism, and radiolabelled CO2 produced by cells were collected and measured by the liquid scintillation device. In addition, glycogen consumption per hour was determined in each group.Results and Conclusion: We found that untreated HL-60 promyolocytic cells use anaerobic glycolytic pathway whereas healthy white blood cells use aerobic glycolysis for energy gain. It was concluded that combined use of Ara-C and Simvastatin might lead to significant increase in the rate of aerobic glycolysis of HL-60 promyelocytic cells and the metabolism of these leukemia cells become more similar to the metabolism of healthy white blood cells which they originate from

Anahtar Kelime:

Konular: Biyokimya ve Moleküler Biyoloji

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	BOYUNAĞA H, DİKMEN Z, KENAR L, SAYGUN O, KELEŞ H, URAL A, LALE M, kosargelir m (2013). The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines. , 31 - 36.
Chicago	BOYUNAĞA Hakan,DİKMEN Z. Günnur,KENAR LEVENT,SAYGUN Oral,KELEŞ HATİCE,URAL Ali Uğur,LALE Mustafa,kosargelir mehmet The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines. (2013): 31 - 36.
MLA	BOYUNAĞA Hakan,DİKMEN Z. Günnur,KENAR LEVENT,SAYGUN Oral,KELEŞ HATİCE,URAL Ali Uğur,LALE Mustafa,kosargelir mehmet The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines. , 2013, ss.31 - 36.
AMA	BOYUNAĞA H,DİKMEN Z,KENAR L,SAYGUN O,KELEŞ H,URAL A,LALE M,kosargelir m The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines. . 2013; 31 - 36.
Vancouver	BOYUNAĞA H,DİKMEN Z,KENAR L,SAYGUN O,KELEŞ H,URAL A,LALE M,kosargelir m The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines. . 2013; 31 - 36.
IEEE	BOYUNAĞA H,DİKMEN Z,KENAR L,SAYGUN O,KELEŞ H,URAL A,LALE M,kosargelir m "The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines." , ss.31 - 36, 2013.
ISNAD	BOYUNAĞA, Hakan vd. "The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines". (2013), 31-36.

APA	BOYUNAĞA H, DİKMEN Z, KENAR L, SAYGUN O, KELEŞ H, URAL A, LALE M, kosargelir m (2013). The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines. Türk Biyokimya Dergisi, 38(1), 31 - 36.
Chicago	BOYUNAĞA Hakan,DİKMEN Z. Günnur,KENAR LEVENT,SAYGUN Oral,KELEŞ HATİCE,URAL Ali Uğur,LALE Mustafa,kosargelir mehmet The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines. Türk Biyokimya Dergisi 38, no.1 (2013): 31 - 36.
MLA	BOYUNAĞA Hakan,DİKMEN Z. Günnur,KENAR LEVENT,SAYGUN Oral,KELEŞ HATİCE,URAL Ali Uğur,LALE Mustafa,kosargelir mehmet The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines. Türk Biyokimya Dergisi, vol.38, no.1, 2013, ss.31 - 36.
AMA	BOYUNAĞA H,DİKMEN Z,KENAR L,SAYGUN O,KELEŞ H,URAL A,LALE M,kosargelir m The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines. Türk Biyokimya Dergisi. 2013; 38(1): 31 - 36.
Vancouver	BOYUNAĞA H,DİKMEN Z,KENAR L,SAYGUN O,KELEŞ H,URAL A,LALE M,kosargelir m The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines. Türk Biyokimya Dergisi. 2013; 38(1): 31 - 36.
IEEE	BOYUNAĞA H,DİKMEN Z,KENAR L,SAYGUN O,KELEŞ H,URAL A,LALE M,kosargelir m "The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines." Türk Biyokimya Dergisi, 38, ss.31 - 36, 2013.
ISNAD	BOYUNAĞA, Hakan vd. "The Effects of Ara-C, Simvastatin and combo therapy on İY energy metabolism of HL-60 promyolocytic leukemia cell lines". Türk Biyokimya Dergisi 38/1 (2013), 31-36.