(E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibits tumor growth via suppression of NF-κB and induction of death receptor 6.
The Maillard reaction products are known to be effective in chemoprevention. Here, we focused on the anti-cancer effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on in vitro and in vivo colon cancer. We analysed the anti-cancer activity of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on colon cancer cells by using cell cycle and apoptosis analysis. To elucidate it's mechanism, NF-κB DNA binding activity, docking model as well as pull-down assay. Further, a xenograft model of colon cancer was studied to test the in vivo effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal. (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibited colon cancer cells (SW620 and HCT116) growth followed by induction of apoptosis in a concentration-dependent manner via down-regulation of NF-κB activity. In docking model as well as pull-down assay, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal directly binds to three amino acid residues of IKKβ, thereby inhibited IKKβ activity in addition to induction of death receptor 6 (DR6) as well as their target apoptotic genes. Finally, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal suppressed anchorage-independent cancer cell growth, and tumor growth in xenograft model accompanied with apoptosis through inhibition of IKKβ/NF-κB activity, and overexpression of DR6. These results suggest that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal inhibits colon cancer cell growth through inhibition of IKKβ/NF-κB activity and induction of DR6 expression.
College of Pharmacy and Medical Research Center, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, South Korea.
Jung Ok
JO
Ban
Young-Suk
YS
Jung
Dae Hwan
DH
Kim
Kyung-Ran
KR
Park
Hyung-Mun
HM
Yun
Nam Jin
NJ
Lee
Hee Pom
HP
Lee
Jeong-Hyun
JH
Shim
Heon-Sang
HS
Jeong
Yun-Hee
YH
Lee
Young Wan
YW
Ham
Sang-Bae
SB
Han
Jin Tae
JT
Hong
D000447:Aldehydes / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010636:Phenols / Q000008:administration & dosage* / Q000737:chemistry; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*
C580808:2,4-bis(p-hydroxyphenyl)-2-butenal; D000447:Aldehydes; D016328:NF-kappa B; D010636:Phenols; D018124:Receptors, Tumor Necrosis Factor; C114109:TNFRSF21 protein, human; D051550:I-kappa B Kinase