Bufalin, a traditional Chinese medicine compound, prevents tumor formation in two murine models of colorectal cancer
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AbstractChemoprevention is cost-effective for colorectal cancer (CRC) when targeted at intermediate- or high-risk populations. Bufalin is a cardiac glycoside extracted from the traditional Chinese medicine (TCM) "Chan Su" which has been used as an anticancer agent. Based on the relative safety of bufalin, we investigated if bufalin could act as a chemoprophylactic agent to prevent colon tumorigenesis in two murine models, namely colitis-associated CRC and Apc germline mutation-developed CRC. Our results revealed that long-term (12-16 weeks) administration of low-dose bufalin (0.5 mg/kg) effectively suppressed tumorigenesis in both CRC models, accompanied by attenuated epithelial cell proliferation (reduced bromodeoxyuridine incorporation, lower levels of cyclin A, cyclin D1, cyclin E and cyclin-dependent kinases-2/4, and higher levels of p21 and p27) and promoted apoptosis (increased TUNEL-positivity and caspase-3/9 cleavages, reduced levels of Bcl-2, Bcl-xL and survivin, and increased levels of Bax and Bak). Bufalin also suppressed the expression of pro-inflammatory mediators (reduced levels of cyclooxygenase-2, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, C-X-C motif chemokine ligand (CXCL)-1, CXCL-2 and CXCL-5) in the colitis-associated CRC model. These effects were associated with the inhibition of oncogenic nuclear factor-κB and phosphoinositide-3-kinase/Akt pathways. Our findings unveil a novel chemoprophylactic action of bufalin in CRC in vivo and provided efficacy data and mechanistic evidence for further clinical evaluation of this TCM compound for CRC chemoprevention in individuals at risk of CRC.
All Author(s) ListXiao SUN, Tony T.H. NG, Kathy W.Y. SHAM, Lin ZHANG, Matthew T.V. CHAN, William K.K. WU, Christopher H.K. CHENG
Journal nameCancer Prevention Research
Year2019
Month10
Volume Number12
Issue Number10
Pages653 - 666
ISSN1940-6207
LanguagesEnglish-United Kingdom

Last updated on 2020-20-10 at 23:03