Immunomolecular evaluation of dihydroartemisinin effects on apoptosis in chronic lymphocytic leukemia cell lines

GÖKÇEN S., BAĞRIAÇIK E. Ü., KAYHAN H., Yağcı M.

LEUKEMIA RESEARCH, cilt.110, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 110
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.leukres.2021.106702
  • 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: Dihydroartemisinin, Chronic lymphocytic leukemia, Apoptosis, CONTROLLED TUMOR PROTEIN, 17P DELETION, ANTICANCER ACTIVITY, THERAPEUTIC TARGET, MUTATIONAL STATUS, GENE-EXPRESSION, IN-VITRO, ARTEMISININ, HEPATOMA, PATHWAY
  • Gazi Üniversitesi Adresli: Evet

Özet

Introduction: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently shown to induce apoptosis in many types of cancer cells. In this study, we aimed to determine the effects of DHA on apoptosis in human chronic lymphocytic leukemia (CLL) cell lines. Methods: The cells were treated separately and combined by DHA and Fludurabine (FLU) during 24, 48 and 72 hours. The cell viabilities determined by XTT method. Following separate and combined treatment of IC50 concentrations of DHA and FLU to the cells during 24 hours, the cells were analyzed by flow cytometry to determine the effects on apopotis staining with AnnexinV FITC and PI. mRNA and protein expression levels of TCTP, Mcl-1, Bcl-2, Bax and Caspase-3 were analyzed to find out the molecular mechanisms of apoptosis by using quantitative real-time PCR and flow cytometric methods. Results: Treatment with DHA alone or in combination with FLU induced apoptosis in a dose dependent manner in CLL cells. DHA alone was more effective than FLU alone or combined treatment with DHA and FLU. Our results suggest that Bcl-2 protein family member Bax was active in the apoptotic response of CLL cells after DHA treatment. Moreover, the apoptotic response induced by DHA was independent from the p53 mutation status of the CLL cells. Conclusion: DHA might be a potential anti-cancer therapeutic for CLL.