Open AccessThe preclinical analysis of TW-37 as a potential anti-colorectal cancer cell agent
Author(s) -
Shun Lei,
Yao Ding,
Yun Fu,
Shuang Wu,
Xiong Xie,
Cancan Wang,
Houjie Liang
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0184501
Subject(s) - autophagy , apoptosis , colorectal cancer , in vivo , cancer research , gene knockdown , cell growth , small hairpin rna , cancer cell , programmed cell death , cell culture , chemistry , growth inhibition , biology , cancer , microbiology and biotechnology , medicine , biochemistry , genetics
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.