摘要

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.
原文英語
文章編號42291
期刊Scientific Reports
7
DOIs
出版狀態已發佈 - 二月 9 2017

指紋

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

引用此文

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.

於: Scientific Reports, 卷 7, 42291, 09.02.2017.

研究成果: 雜誌貢獻文章

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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}",
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AU - Wu, Yi Wen

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AU - Yang, Chia Ron

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