CCY-1a-E2 induces G2/M phase arrest and apoptotic cell death in HL-60 leukemia cells through cyclin-dependent kinase 1 signaling and the mitochondria-dependent caspase pathway

Abstract

Our previous study demonstrated that 2-[(3-methoxybenzyl)oxy]benzaldehyde (CCY-1a-E2) is a potent compound that acts against multiple human leukemia cell lines. CCY-1a-E2 was also shown to have efficacious anti‑leukemic activity in vivo. However, the molecular mechanism of action of CCY‑1a‑E2 attributed to its anticancer effect remains poorly understood. In the present study, CCY‑1a‑E2 suppressed cell viability in multiple leukemia cell lines (HL‑60, K562, KG‑1 and KG‑1a) via inhibition of cell proliferation, cell cycle arrest and induction of apoptosis. CCY‑1a‑E2 exhibited a marked toxic effect on HL‑60 cells and displayed low cytotoxicity in normal human peripheral blood mononuclear cells (PBMCs). Results from flow cytometric analysis indicated that CCY‑1a‑E2 promoted G2/M phase arrest and promoted apoptosis in the HL‑60 cells. CCY‑1a‑E2 treatment upregulated cyclin B, cyclin‑dependent kinase 1 (CDK1), cell division cycle 25C (cdc25C) and p21 protein expression. CCY‑1a‑E2 caused apoptotic cell death and DNA fragmentation as determined by 4',6‑diamidino‑2‑phenylindole (DAPI) staining and DNA gel electrophoresis. Elevated activities of caspase‑8, ‑9 and ‑3 were observed during CCY‑1a‑E2‑induced cell apoptosis; their specific inhibitors were found to block CCY‑1a‑E2‑induced apoptosis, respectively. Moreover, CCY‑1a‑E2 time‑dependently disrupted the mitochondrial membrane potential (ΔΨm), and it enhanced the protein levels of Fas/CD95, cytochrome c, Bax, cleaved PARP, as well as attenuated Bcl‑2 expression in the HL‑60 cells. Our results provide direct evidence that supports the future potential therapeutic application of CCY-1a-E2 in leukemia.

The outer membrane protein Tp92 of Treponema pallidum induces human mononuclear cell death and IL‐8 secretion

“…Apoptosis is a type of cell death that is not related with inflammation but is dependent on caspase. It is believed that caspase‐1, ‐4, ‐5 and ‐11 are associated with pyroptosis, while caspase‐3, ‐6, ‐7, ‐8 and ‐9 are associated with apoptosis . The present study also reveals that Tp92 induces the apoptosis of THP‐1 cells, which is dependent on the concentration and duration of Tp92 treatment.…”

“…Count Count Count and -9 are associated with apoptosis. [38][39][40][41][42] The present study also reveals that Tp92 induces the apoptosis of THP-1 cells, which is dependent on the concentration and duration of Tp92 treatment. Fas-associated death domain and induces apoptosis by activating caspase-3, -6 and -7 via the activation of caspase-8.…”

YC-1 induces G0/G1phase arrest and mitochondria-dependent apoptosis in cisplatin-resistant human oral cancer CAR cells

“…The cell cycle profiling and the data analysis were determined utilizing a Muse Cell Analyzer (Merck Millipore, Hayward, CA, USA) [93–98]. …”

ITR‑284 modulates cell differentiation in human chronic myelogenous leukemia K562 cells

“…One-way analysis of variance (ANOVA) with a one-tailed Student's t-test was used for multiple comparisons among groups. A value of p<0.05 was considered statistically significant (5,33,35).…”