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

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

Research output: Contribution to journalArticle

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 (ΔΦm) 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.

LanguageEnglish (US)
Pages1331-1337
Number of pages7
JournalOncology reports
Volume39
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

U937 Cells
G2 Phase
Cell Division
Leukemia
Propidium
Apoptosis
Cell Survival
bcl-2 Homologous Antagonist-Killer Protein
BH3 Interacting Domain Death Agonist Protein
Staining and Labeling
bcl-2-Associated X Protein
K562 Cells
Caspase 9
Agar Gel Electrophoresis
Mitochondrial Membrane Potential
HL-60 Cells
Annexin A5
DNA Fragmentation
Cytochromes c
2-phenyl-4-oxohydroquinoline

Keywords

  • Apoptosis
  • G/M phase
  • Leukemia cells
  • YT-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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.

In: Oncology reports, Vol. 39, No. 3, 01.03.2018, p. 1331-1337.

Research output: Contribution to journalArticle

Lin, Meng Wei ; Yang, Jai Sing ; Lu, Chi Cheng ; Lin, Chingju ; Kuo, Sheng Chu ; Tsai, Fuu-Jen ; Lee, Miau Rong. / 2-Phenyl-4-quinolone (YT-1) induces G2/M phase arrest and an intrinsic apoptotic mechanism in human leukemia cells. In: Oncology reports. 2018 ; Vol. 39, No. 3. pp. 1331-1337.
@article{f4156c024d804e12877d9340cd6ff1b4,
title = "2-Phenyl-4-quinolone (YT-1) induces G2/M phase arrest and an intrinsic apoptotic mechanism in human leukemia cells",
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 (ΔΦm) 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.",
keywords = "Apoptosis, G/M phase, Leukemia cells, YT-1",
author = "Lin, {Meng Wei} and Yang, {Jai Sing} and Lu, {Chi Cheng} and Chingju Lin and Kuo, {Sheng Chu} and Fuu-Jen Tsai and Lee, {Miau Rong}",
year = "2018",
month = "3",
day = "1",
doi = "10.3892/or.2017.6170",
language = "English (US)",
volume = "39",
pages = "1331--1337",
journal = "Oncology Reports",
issn = "1021-335X",
publisher = "Spandidos Publications",
number = "3",

}

TY - JOUR

T1 - 2-Phenyl-4-quinolone (YT-1) induces G2/M phase arrest and an intrinsic apoptotic mechanism in human leukemia cells

AU - Lin, Meng Wei

AU - Yang, Jai Sing

AU - Lu, Chi Cheng

AU - Lin, Chingju

AU - Kuo, Sheng Chu

AU - Tsai, Fuu-Jen

AU - Lee, Miau Rong

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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 (ΔΦm) 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.

AB - 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 (ΔΦm) 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.

KW - Apoptosis

KW - G/M phase

KW - Leukemia cells

KW - YT-1

UR - http://www.scopus.com/inward/record.url?scp=85041699396&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041699396&partnerID=8YFLogxK

U2 - 10.3892/or.2017.6170

DO - 10.3892/or.2017.6170

M3 - Article

VL - 39

SP - 1331

EP - 1337

JO - Oncology Reports

T2 - Oncology Reports

JF - Oncology Reports

SN - 1021-335X

IS - 3

ER -