Mechanistic Study of Triazole Based Aminodiol Derivatives in Leukemic Cells-Crosstalk between Mitochondrial Stress-Involved Apoptosis and Autophagy.

ABSTRACT: Various derivatives that mimic ceramide structures by introducing a triazole to connect the aminodiol moiety and long alkyl chain have been synthesized and screened for their anti-leukemia activity. SPS8 stood out among the derivatives, showing cytotoxic selectivity between leukemic cell lines and human peripheral blood mononuclear cells (about ten times). DAPI nuclear staining and H&E staining revealed DNA fragmentation under the action of SPS8. SPS8 induced an increase in intracellular Ca2+ levels and mitochondrial stress in HL-60 cells identified by the loss of mitochondrial membrane potential, transmission electron microscopy (TEM) examination, and altered expressions of Bcl-2 family proteins. SPS8 also induced autophagy through the detection of Atg5, beclin-1, and LC3 II protein expre

SUBMITTER: Chan SH 

PROVIDER: S-EPMC7177546 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature