Open AccessCalpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme
Author(s) -
Marciel Michael P.,
Rose Aaron H.,
Martinez Verena,
Horio David T.,
Hashimoto Ann S.,
Hoffmann FuKun W.,
Bertino Pietro,
Hoffmann Peter R.
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1260
Subject(s) - calpain , colorectal cancer , cell culture , cancer research , apoptosis , chemotherapy , cancer , medicine , cancer cell , programmed cell death , cell , enzyme , chemistry , biology , biochemistry , genetics
Calpain‐2 levels are higher in colorectal tumors resistant to chemotherapy and previous work showed calpain‐2 inhibitor therapy reduced inflammation‐driven colorectal cancer, but direct effects of the inhibitor on colon cancer cells themselves were not demonstrated. In the present study, five human colon cancer cell lines were directly treated with a calpain‐2 inhibitor and results showed increased cell death in 4 of 5 cell lines and decreased anchorage‐independent growth for all cell five lines. When tested for levels of calpain‐2, three cell lines exhibited increasing levels of this enzyme: HCT 15 (low), HCC 2998 (medium), and HCT 116 (significantly higher). This was consistent with gel shift assays showing that calpain‐2 inhibitor reduced of NF ‐ κ B nuclear translocation most effectively in HCT 116 cells. Ability of calpain‐2 inhibitor to impede tumor progression in vivo was evaluated using intrarectal transplant of luciferase‐expressing cells for these three cell lines. Results showed that calpain‐2 inhibitor therapy reduced tumor growth and increased survival only in mice injected with HCT 116 cells. These data suggest calpain‐2 inhibitor treatment may be most effective on colorectal tumors expressing highest levels of calpain‐2.