Acceleration of slow autophagy flux induced by arabinofuranosyl cytidine improves its antileukemic effectiveness in M-NFS-60 cells

Turkish Journal of Biology

article

FOUAD, SALWA¹  ELSOKKARY, GAMAL¹  SHAKOR, ABO BAKR ABDEL¹ 

[1] Laboratory of molecular cell biology, Department of Zoology, Faculty of Science, Assiut University

关键词: Arabinofuranosyl cytidine;    hyperthermia;    autophagy;    myelogenous leukemia;    M-NFS-60 cells;   

DOI  :  10.55730/1300-0152.2619

学科分类：生物科学（综合）

来源: Scientific and Technical Research Council of Turkey - TUBITAK

【 摘 要 】

Arabinofuranosyl cytidine (AraC) is an analog of deoxycytidine used as an anticancer drug for leukemic patients. The effective dose always produces severe complications. The present study investigated the modulation of autophagy and its impact on the cytotoxicity of AraC toward murine myelogenous leukemia cells (M-NFS-60). Autophagy was inhibited by NH4Cl or Bafilomycin A1 or enhanced by amino acid starvation, glucose starvation, mild hyperthermia (41 °C), or rapamycin (Rap). Cells were treated with different concentrations, 0 to 2 µM, of AraC in the presence or absence of autophagy modulators. AraC-induced apoptosis is combined with autophagy, especially at lower concentrations. This autophagy is characterized by a slow flux, as indicated by levels of LC3B II and P62 proteins. Inhibition of autophagy did not alter cleaved caspase 3 levels (c-casp.3) or cell viability measured by MTT assays. Conversely, acceleration of AraC-induced autophagy by co-treatment with autophagy inducers reduced cell viability and increased c-casp.3 and c-PARP levels. Further, c-PARP levels were reduced in the presence of caspase inhibitor, Z-VAD-FMK. Enhancement of slow autophagic flux induced by low concentrations of AraC significantly increased the cytotoxicity of AraC toward M-NFS-60 cells. Such coadministration of autophagy inducers might improve the efficacy of AraC treatment and reduce effective doses.

【 授权许可】

Unknown