Affordable Access

deepdyve-link deepdyve-link
Publisher Website

Thiocolchicoside exhibits anticancer effects through downregulation of NF-κB pathway and its regulated gene products linked to inflammation and cancer.

Authors
  • Reuter, Simone
  • Prasad, Sahdeo
  • Phromnoi, Kanokkarn
  • Ravindran, Jayaraj
  • Sung, Bokyung
  • Yadav, Vivek R
  • Kannappan, Ramaswamy
  • Chaturvedi, Madan M
  • Aggarwal, Bharat B
Type
Published Article
Journal
Cancer prevention research (Philadelphia, Pa.)
Publication Date
Nov 01, 2010
Volume
3
Issue
11
Pages
1462–1472
Identifiers
DOI: 10.1158/1940-6207.CAPR-10-0037
PMID: 20978115
Source
Medline
License
Unknown

Abstract

The discovery of new uses for older, clinically approved drugs is one way to expedite drug development for cancer. Thiocolchicoside, a semisynthetic colchicoside from the plant Gloriosa superba, is a muscle relaxant and used to treat rheumatologic and orthopedic disorders because of its analgesic and anti-inflammatory mechanisms. Given that activation of the transcription factor NF-κB plays a major role in inflammation and tumorigenesis, we postulated that thiocolchicoside would inhibit NF-κB and exhibit anticancer effects through the modulation of NF-κB-regulated proteins. We show that thiocolchicoside inhibited proliferation of leukemia, myeloma, squamous cell carcinoma, breast, colon, and kidney cancer cells. Formation of tumor colonies was also suppressed by thiocolchicoside. The colchicoside induced apoptosis, as indicated by caspase-3 and poly(ADP-ribose) polymerase cleavage, and suppressed the expression of cell survival [e.g., Bcl-2, X-linked inhibitor of apoptosis (XIAP), MCL-1, bcl-xL, cIAP-1, cIAP-2, and cFLIP] proteins. Cell proliferation biomarkers such as c-MYC and phosphorylation of phosphoinositide 3-kinase and glycogen synthase kinase 3β were also blocked by thiocolchicoside. Because most cell survival and proliferation gene products are regulated by NF-κB, we studied the effect of thiocolchicoside on this transcription factor and found that thiocolchicoside inhibited NF-κB activation, degradation of inhibitory κBα (IκBα), IκBα ubiquitination, and phosphorylation, abolished the activation of IκBα kinase, and suppressed p65 nuclear translocation. This effect of thiocolchicoside on the NF-κB pathway led to inhibition of NF-κB reporter activity and cyclooxygenase-2 promoter activity. Our results indicate that thiocolchicoside exhibits anticancer activity through inhibition of NF-κB and NF-κB-regulated gene products, which provides novel insight into a half-century old drug.

Report this publication

Statistics

Seen <100 times