Securin enhances the anti-cancer effects of 6-methoxy-3-(3′,4′,5′-trimethoxy-benzoyl)-1H-indole (BPR0L075) in human colorectal cancer cells

Ho Hsing Tseng, Qiu Yu Chuah, Pei Ming Yang, Chiung Tong Chen, Jung Chi Chao, Ming Der Lin, Shu Jun Chiu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

BPR0L075 [6-methoxy-3-(3′,4′,5′-trimethoxy-benzoyl)-1H-indole] is a novel anti-microtubule drug with anti-tumor and anti-angiogenic activities in vitro and in vivo. Securin is required for genome stability, and is expressed abundantly in most cancer cells, promoting cell proliferation and tumorigenesis. In this study, we found that BPR0L075 efficiently induced cell death of HCT116 human colorectal cancer cells that have higher expression levels of securin. The cytotoxicity of BPR0L075 was attenuated in isogenic securin-null HCT116 cells. BPR0L075 induced DNA damage response, G2/M arrest, and activation of the spindle assembly checkpoint in HCT116 cells. Interestingly, BPR0L075 induced phosphorylation of securin. BPR0L075 withdrawal resulted in degradation of securin, mitotic exit, and mitotic catastrophe, which were attenuated in securin-null cells. Inhibition of cdc2 decreased securin phosphorylation, G2/M arrest and cell death induced by BPR0L075. Moreover, BPR0L075 caused cell death through a caspase-independent mechanism and activation of JNK and p38 MAPK pathways. These findings provided evidence for the first time that BPR0L075 treatment is beneficial for the treatment of human colorectal tumors with higher levels of securin. Thus, we suggest that the expression levels of securin may be a predictive factor for application in anti-cancer therapy with BPR0L075 in human cancer cells.

Original languageEnglish
Article numbere36006
JournalPLoS One
Volume7
Issue number4
DOIs
Publication statusPublished - Apr 26 2012
Externally publishedYes

Fingerprint

Securin
indoles
colorectal neoplasms
cell death
Colorectal Neoplasms
Cells
mitogen-activated protein kinase
phosphorylation
Neoplasms
neoplasms
caspases
cells
Cell death
DNA damage
carcinogenesis
microtubules
cytotoxicity
cell proliferation
HCT116 Cells
Null Lymphocytes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Securin enhances the anti-cancer effects of 6-methoxy-3-(3′,4′,5′-trimethoxy-benzoyl)-1H-indole (BPR0L075) in human colorectal cancer cells. / Tseng, Ho Hsing; Chuah, Qiu Yu; Yang, Pei Ming; Chen, Chiung Tong; Chao, Jung Chi; Lin, Ming Der; Chiu, Shu Jun.

In: PLoS One, Vol. 7, No. 4, e36006, 26.04.2012.

Research output: Contribution to journalArticle

Tseng, Ho Hsing ; Chuah, Qiu Yu ; Yang, Pei Ming ; Chen, Chiung Tong ; Chao, Jung Chi ; Lin, Ming Der ; Chiu, Shu Jun. / Securin enhances the anti-cancer effects of 6-methoxy-3-(3′,4′,5′-trimethoxy-benzoyl)-1H-indole (BPR0L075) in human colorectal cancer cells. In: PLoS One. 2012 ; Vol. 7, No. 4.
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