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

Abstract

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 CO 2 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. Key Words: Warburg effect, HL-60 cell lines, energy metabolism, simvastatin, Ara-C. Conflict of Interest:Authors declare no conflict of interest. ÖZETAmaç: Kanser hücrelerinde metabolik yönelim, ortamın oksijen içeriği ve substrat konsantrasyonuna göre düzenlenmektedir. Kanser hücresinin enerji metabolizmasının düzenlen-mesine 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. İnkübas-yon sonrası, karbonhidrat katabolizmasının son ürünlerinden laktat ve hücreler tarafından üretilen radyoaktif işaretli CO 2 toplanarak likit sintilasyon cihazında ölçüldü. Ayrıca her bir grupta saatteki glikojen tüketimi hesaplandı. Bulgular ve Tartışma: Çalışmanın sonucunda enerji eldesinde HL-60 promyelositik hücre-lerinin anaerobik glikolizi, sağlıklı...

Induction of P3NS1 Myeloma Cell Death and Cell Cycle Arrest by Simvastatin and/or γ-Radiation

“…Ibrahim Y Abdelrahman 1 , Reham Helwa 2 *, Hausein Elkashef 1 , Nagwa H A Hassan 2 2011), breast cancer (Bjarnadottir et al, 2013), Killing leukemia cell line (Boyunağa, 2013), Lymphoblast and myeloma cells (Cafforio et al, 2005), Lung cancer (Tan et al, 2013), Prostate cancer (Goc et al, 2012), and hepatic cancer (Relja et al, 2010).…”