2-Phenyl-4-quinolone (YT-1) induces G2/M phase arrest and an intrinsic apoptotic mechanism in human leukemia cells

Lin,Meng‑Wei; Yang,Jai‑Sing; Lu,Chi‑Cheng; Lin,Chingju; Kuo,Sheng‑Chu; Tsai,Fuu‑Jen; Lee,Miau‑Rong

doi:10.3892/or.2017.6170

2-Phenyl-4-quinolone (YT-1) induces G2/M phase arrest and an intrinsic apoptotic mechanism in human leukemia cells

Authors:
- Meng‑Wei Lin
- Jai‑Sing Yang
- Chi‑Cheng Lu
- Chingju Lin
- Sheng‑Chu Kuo
- Fuu‑Jen Tsai
- Miau‑Rong Lee
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Affiliations: Department of Nursing, Cardinal Tien Junior College of Healthcare and Management, New Taipei 231, Taiwan, R.O.C., Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Pharmacy, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, R.O.C., Department of Physiology, China Medical University, Taichung 404, Taiwan, R.O.C., School of Pharmacy,, China Medical University, Taichung 404, Taiwan, R.O.C., Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan, R.O.C., Department of Biochemistry, China Medical University, Taichung 404, Taiwan, R.O.C.
Published online on: December 20, 2017 https://doi.org/10.3892/or.2017.6170
Pages: 1331-1337

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Abstract

The present study aimed to investigate the biological effects of the new compound 2‑phenyl‑4‑quinolone (YT‑1) on human leukemia cells. Cell viability was determined by propidium iodide (PI) exclusion method followed by flow cytometry. Our results showed that YT‑1 inhibited the cell viability and resulted in morphologic changes to the U937, HL‑60 and K562 cells, respectively. Among them, U937 cells were the most sensitive cell line. On the contrary, YT‑1 had no cytotoxic effects on human fetal skin fibroblast WS1 cells. Flow cytometric analysis indicated that YT‑1 induced G2/M phase arrest and apoptosis (sub‑G1 population) in U937 cells. The presence of apoptotic bodies evidenced by DAPI staining and DNA fragmentation detected by agarose gel electrophoresis further supported the induction of apoptosis in the YT‑1‑treated U937 cells. Annexin V/PI staining of U937 cells confirmed that the early apoptotic event occurred after YT‑1 exposure. YT‑1 disrupted the mitochondrial membrane potential (ΔΨm) in a time‑dependent manner. YT‑1 increased the protein levels of Bax and Bak but decreased Bcl‑2 and Bid protein levels in U937 cells in a time‑dependent manner. In addition, YT‑1 stimulated the expression of cytochrome c and proteolytic activation of caspase‑3 and caspase‑9 after exposure to YT‑1 in U937 cells. In summary, YT‑1 suppressed the viability of U937 leukemia cells through the intrinsic apoptosis pathway. YT‑1 is a potential chemotherapeutic candidate for the treatment of leukemia.

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