Abstract

Cancers are the major cause of death worldwide. Chemotherapy using cytotoxic drugs and targeted therapy is required when surgery is difficult, ineffective, or impossible. We previously synthesized the novel synthetic 1-benzylindole derivative 21-900 and found that it inhibits histone deacetylase (HDAC) activities and tubulin assembly. Here we tested its effects on the human leukaemia cell lines HL-60 and MOLT-4 in vitro and in vivo. We found that its potent cytotoxic effects were mediated through cell cycle arrest at the G2/M phase, which increased the population of sub-G1 cells, leading to apoptosis. Further, tubulin was depolymerized by 21-900 in a manner similar to that of vincristine, leading to disruption of microtubule dynamics and increased levels of the mitotic marker MPM-2. Further, 21-900 increased the expression of cleavage form of poly (ADP-ribose) polymerase (PARP), caspase 3, 7 (cleavage form), and pro-apoptotic protein BAK and decreased the expression of pro-survival BCL-2-family proteins BCL-2, MCL-1, and BID pro-form, leading to the induction of apoptosis. The growth of tumours in nude mice formed by xenografts of HL-60 and MOLT-4 cells was significantly inhibited by 21-900 without causing the mice to lose body weight. These findings indicate that 21-900 may serve as a potent anti-leukaemia drug.

Original languageEnglish
Article number42291
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - Feb 9 2017

Fingerprint

Tubulin
Leukemia
Apoptosis
Caspase 7
Drug Therapy
Apoptosis Regulatory Proteins
Histone Deacetylases
Poly(ADP-ribose) Polymerases
G2 Phase
Vincristine
Cell Cycle Checkpoints
Heterografts
Nude Mice
Microtubules
Caspase 3
Cell Division
Cause of Death
Neoplasms
Body Weight
Cell Line

ASJC Scopus subject areas

  • General

Cite this

Anti-leukemia effects of the novel synthetic 1-benzylindole derivative 21-900 in vitro and in vivo. / Huangfu, Wei Chun; Chao, Min Wu; Cheng, Chun Chun; Wei, Yu Chieh; Wu, Yi Wen; Liou, Jing Ping; Hsiao, George; Lee, Yu Ching; Yang, Chia Ron.

In: Scientific Reports, Vol. 7, 42291, 09.02.2017.

Research output: Contribution to journalArticle

@article{49373926b6624de0a332f092910fa616,
title = "Anti-leukemia effects of the novel synthetic 1-benzylindole derivative 21-900 in vitro and in vivo",
abstract = "Cancers are the major cause of death worldwide. Chemotherapy using cytotoxic drugs and targeted therapy is required when surgery is difficult, ineffective, or impossible. We previously synthesized the novel synthetic 1-benzylindole derivative 21-900 and found that it inhibits histone deacetylase (HDAC) activities and tubulin assembly. Here we tested its effects on the human leukaemia cell lines HL-60 and MOLT-4 in vitro and in vivo. We found that its potent cytotoxic effects were mediated through cell cycle arrest at the G2/M phase, which increased the population of sub-G1 cells, leading to apoptosis. Further, tubulin was depolymerized by 21-900 in a manner similar to that of vincristine, leading to disruption of microtubule dynamics and increased levels of the mitotic marker MPM-2. Further, 21-900 increased the expression of cleavage form of poly (ADP-ribose) polymerase (PARP), caspase 3, 7 (cleavage form), and pro-apoptotic protein BAK and decreased the expression of pro-survival BCL-2-family proteins BCL-2, MCL-1, and BID pro-form, leading to the induction of apoptosis. The growth of tumours in nude mice formed by xenografts of HL-60 and MOLT-4 cells was significantly inhibited by 21-900 without causing the mice to lose body weight. These findings indicate that 21-900 may serve as a potent anti-leukaemia drug.",
author = "Huangfu, {Wei Chun} and Chao, {Min Wu} and Cheng, {Chun Chun} and Wei, {Yu Chieh} and Wu, {Yi Wen} and Liou, {Jing Ping} and George Hsiao and Lee, {Yu Ching} and Yang, {Chia Ron}",
year = "2017",
month = "2",
day = "9",
doi = "10.1038/srep42291",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Anti-leukemia effects of the novel synthetic 1-benzylindole derivative 21-900 in vitro and in vivo

AU - Huangfu, Wei Chun

AU - Chao, Min Wu

AU - Cheng, Chun Chun

AU - Wei, Yu Chieh

AU - Wu, Yi Wen

AU - Liou, Jing Ping

AU - Hsiao, George

AU - Lee, Yu Ching

AU - Yang, Chia Ron

PY - 2017/2/9

Y1 - 2017/2/9

N2 - Cancers are the major cause of death worldwide. Chemotherapy using cytotoxic drugs and targeted therapy is required when surgery is difficult, ineffective, or impossible. We previously synthesized the novel synthetic 1-benzylindole derivative 21-900 and found that it inhibits histone deacetylase (HDAC) activities and tubulin assembly. Here we tested its effects on the human leukaemia cell lines HL-60 and MOLT-4 in vitro and in vivo. We found that its potent cytotoxic effects were mediated through cell cycle arrest at the G2/M phase, which increased the population of sub-G1 cells, leading to apoptosis. Further, tubulin was depolymerized by 21-900 in a manner similar to that of vincristine, leading to disruption of microtubule dynamics and increased levels of the mitotic marker MPM-2. Further, 21-900 increased the expression of cleavage form of poly (ADP-ribose) polymerase (PARP), caspase 3, 7 (cleavage form), and pro-apoptotic protein BAK and decreased the expression of pro-survival BCL-2-family proteins BCL-2, MCL-1, and BID pro-form, leading to the induction of apoptosis. The growth of tumours in nude mice formed by xenografts of HL-60 and MOLT-4 cells was significantly inhibited by 21-900 without causing the mice to lose body weight. These findings indicate that 21-900 may serve as a potent anti-leukaemia drug.

AB - Cancers are the major cause of death worldwide. Chemotherapy using cytotoxic drugs and targeted therapy is required when surgery is difficult, ineffective, or impossible. We previously synthesized the novel synthetic 1-benzylindole derivative 21-900 and found that it inhibits histone deacetylase (HDAC) activities and tubulin assembly. Here we tested its effects on the human leukaemia cell lines HL-60 and MOLT-4 in vitro and in vivo. We found that its potent cytotoxic effects were mediated through cell cycle arrest at the G2/M phase, which increased the population of sub-G1 cells, leading to apoptosis. Further, tubulin was depolymerized by 21-900 in a manner similar to that of vincristine, leading to disruption of microtubule dynamics and increased levels of the mitotic marker MPM-2. Further, 21-900 increased the expression of cleavage form of poly (ADP-ribose) polymerase (PARP), caspase 3, 7 (cleavage form), and pro-apoptotic protein BAK and decreased the expression of pro-survival BCL-2-family proteins BCL-2, MCL-1, and BID pro-form, leading to the induction of apoptosis. The growth of tumours in nude mice formed by xenografts of HL-60 and MOLT-4 cells was significantly inhibited by 21-900 without causing the mice to lose body weight. These findings indicate that 21-900 may serve as a potent anti-leukaemia drug.

UR - http://www.scopus.com/inward/record.url?scp=85012031782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85012031782&partnerID=8YFLogxK

U2 - 10.1038/srep42291

DO - 10.1038/srep42291

M3 - Article

AN - SCOPUS:85012031782

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 42291

ER -