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The preclinical analysis of TW-37 as a potential anti-colorectal cancer cell agent.

TW-37 is a novel, potent and non-peptide Bcl-2 small-molecule inhibitor. Its activity in colorectal cancer (CRC) cells is studied. In both HCT-116 cells and primary human colon cancer cells, treatment with TW-37 at only nM concentration efficiently inhibited cell survival and proliferation. TW-37 al... Full description

Journal Title: PloS one 2017, Vol.12(10), p.e0184501
Main Author: Lei, Shun
Other Authors: Ding, Yao , Fu, Yun , Wu, Shuang , Xie, Xiong , Wang, Cancan , Liang, Houjie
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0184501
Link: http://search.proquest.com/docview/1955611075/?pq-origsite=primo
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title: The preclinical analysis of TW-37 as a potential anti-colorectal cancer cell agent.
format: Article
creator:
  • Lei, Shun
  • Ding, Yao
  • Fu, Yun
  • Wu, Shuang
  • Xie, Xiong
  • Wang, Cancan
  • Liang, Houjie
subjects:
  • Animals–Drug Effects
  • Apoptosis–Pharmacology
  • Benzamides–Therapeutic Use
  • Cell Proliferation–Drug Effects
  • Colorectal Neoplasms–Drug Therapy
  • Hct116 Cells–Pathology
  • Humans–Pharmacology
  • Mice–Therapeutic Use
  • Mice, Scid–Therapeutic Use
  • Sulfones–Therapeutic Use
  • Xenograft Model Antitumor Assays–Therapeutic Use
  • Benzamides
  • Sulfones
  • Tw-37 Compound
ispartof: PloS one, 2017, Vol.12(10), p.e0184501
description: TW-37 is a novel, potent and non-peptide Bcl-2 small-molecule inhibitor. Its activity in colorectal cancer (CRC) cells is studied. In both HCT-116 cells and primary human colon cancer cells, treatment with TW-37 at only nM concentration efficiently inhibited cell survival and proliferation. TW-37 also induced caspase-3/9 and apoptosis activation in CRC cells. Feedback autophagy activation was observed in TW-37-treated CRC cells. Reversely pharmacological autophagy inhibition or Beclin-1 knockdown by targeted-shRNA potentiated TW-37-induced apoptosis and killing of CRC cells. In vivo, intravenous injection of TW-37 inhibited HCT-116 tumor growth in mice. TW-37's anti-tumor activity was further potentiated against Beclin-1-silenced HCT-116 tumors. Together, targeting Bcl-2 family protein by TW-37 efficiently inhibits CRC cell growth in vitro and in vivo. Inhibition of feedback autophagy activation could further sensitize TW-37.
language: eng
source:
identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0184501
fulltext: fulltext
issn:
  • 19326203
  • 1932-6203
url: Link


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titleThe preclinical analysis of TW-37 as a potential anti-colorectal cancer cell agent.
creatorLei, Shun ; Ding, Yao ; Fu, Yun ; Wu, Shuang ; Xie, Xiong ; Wang, Cancan ; Liang, Houjie
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identifierE-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0184501
subjectAnimals–Drug Effects ; Apoptosis–Pharmacology ; Benzamides–Therapeutic Use ; Cell Proliferation–Drug Effects ; Colorectal Neoplasms–Drug Therapy ; Hct116 Cells–Pathology ; Humans–Pharmacology ; Mice–Therapeutic Use ; Mice, Scid–Therapeutic Use ; Sulfones–Therapeutic Use ; Xenograft Model Antitumor Assays–Therapeutic Use ; Benzamides ; Sulfones ; Tw-37 Compound
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descriptionTW-37 is a novel, potent and non-peptide Bcl-2 small-molecule inhibitor. Its activity in colorectal cancer (CRC) cells is studied. In both HCT-116 cells and primary human colon cancer cells, treatment with TW-37 at only nM concentration efficiently inhibited cell survival and proliferation. TW-37 also induced caspase-3/9 and apoptosis activation in CRC cells. Feedback autophagy activation was observed in TW-37-treated CRC cells. Reversely pharmacological autophagy inhibition or Beclin-1 knockdown by targeted-shRNA potentiated TW-37-induced apoptosis and killing of CRC cells. In vivo, intravenous injection of TW-37 inhibited HCT-116 tumor growth in mice. TW-37's anti-tumor activity was further potentiated against Beclin-1-silenced HCT-116 tumors. Together, targeting Bcl-2 family protein by TW-37 efficiently inhibits CRC cell growth in vitro and in vivo. Inhibition of feedback autophagy activation could further sensitize TW-37.
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