Assessment of azithromycin as an anticancer agent for treatment of imatinib sensitive and resistant CML cells

Özkan T., Hekmatshoar Y., Karabay A. Z., Koç A., Altınok Güneş B., Gurel A. K., ...Daha Fazla

LEUKEMIA RESEARCH, cilt.102, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 102
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.leukres.2021.106523
  • Dergi Adı: LEUKEMIA RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Azithromycin, Imatinib resistance, Chronic myeloid leukemia, Apoptosis, CANCER STEM-CELLS, CHRONIC MYELOID-LEUKEMIA, MULTIDRUG-RESISTANCE, ANTIBIOTICS, MITOCHONDRIA, APOPTOSIS
  • Ankara Üniversitesi Adresli: Evet

Özet

Introduction: Chronic Myeloid Leukemia (CML) is a hematological disease which is characterized by the presence of BCR-ABL fusion protein. Imatinib (IMA), a tyrosine kinase inhibitor of BCR-ABL, is used as a frontline treatment.Although IMA aids in killing a majority of leukemia cells, it may not kill CML stem cells which are the primary roots of disease and therapy resistance. Recently, antimicrobial drugs have been gaining attention because of their selective targeting of cancer cells. Therefore, we now ask if combinational therapy of IMA with a targeted antimicrobial drug Azithromycin (AZT) can enhance the treatment efficiency in IMA resistant CML. Methods: K562S (IMA sensitive) and K562R (IMA resistant) cells were treated with increasing concentrations of AZT to determine its effects on cell proliferation and apoptosis. Cell viability, apoptosis, caspase3/7 activity and P-glycoprotein (Pgp) function were investigated with spectrophotometric MTT assay and flow cytometric Annexin V staining, caspase 3/7 activity, and Rhodamine123 staining assays respectively. The expression levels of pro-apoptotic (BAX, BAD and BIM), anti-apoptotic (BCL-XL and BCL-2) and drug transporter (MDR-1 and MRP-1) genes were assessed with qRT-PCR.