Camphorataimide B suppresses the metastasis of human colorectal cancer cell by inhibiting Smad/FAK/Akt axis and promoting degradation of Snail/BMP4 complex

Chi-Chou Huang ^a,b,1, Chia-Hung Hung ^c,1, Yi-Ju Lee ^d,e, Tsui-Hwa Tseng ^f,Yean-Jang Lee ^g, Shao-Hsuan Kao ^c,h,**, Chau-Jong Wang ^c,h,i,*

a Department of Colorectal Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan

b School of Medicine, Chung Shan Medical University, Taichung, Taiwan

c Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan

d Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan

e Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan

f Department of Medical Chemistry, Chung Shan Medical University, Taichung, Taiwan

g Department of Chemistry, National Changhua University of Education, Changhua, Taiwan

h Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

i Department of Health Diet and Industry Management, Chung Shan Medical University, Taichung, Taiwan

Camphorataimide B (CamB) has anticancer activities against several tumors. Here, we aimed to investigate the mechanism(s) by which CamB inhibits metastasis of colorectal cancer (CRC) cells. Low-dose CamB did not affect the cell viability and cell cycle progression of CRC cells, but significantly inhibited the metastatic potentials of CRC cells. Mechanically, CamB reduced the protein and Mrna expression of BMP4, and inhibited Smad and FAK/Src/Akt signaling. CamB also decreased Snail levels by promoting its degradation via proteasome and thereafter reduced Snailmediated BMP4 transcription. Moreover, CamB considerably inhibited the in vivo metastasis of DLD-1 cells in xenograft mice.

Keywords: Bone morphogenetic protein 4, Camphorataimide-B, Colorectal cancer, FAK, Snail

https://doi.org/10.38212/2224-6614.3405

(https://www.jfda-online.com/journal/vol30/iss2/7/)