Norcantharidin induces HT-29 colon cancer cell apoptosis through the alphavbeta6-extracellular signal-related kinase signaling pathway.
Norcantharidin has been used as an efficacious anticancer drug in China for many years, but its true mechanism remains poorly understood. Intriguingly, in an in vitro series study of anticancer drugs, we found that norcantharidin can effectively inhibit epithelial tumor cells from expressing integrin alphavbeta6. Our previous studies have confirmed that integrin alphavbeta6 is closely relevant to malignant epithelial cell tumor biology behavior, and it can promote cancer cells to invade and metastasize through a special alphavbeta6-extracellular signal-related kinase (ERK) direct signaling pathway. In this study, we investigated the relationship between the norcantharidin anticancer mechanism and integrin alphavbeta6. After HT-29 colon cancer cells were treated with norcantharidin, cell apoptosis increased remarkably. The expression of alphavbeta6 and the amount of p-ERK decreased substantially; simultaneously, the linkage between alphavbeta6 and ERK was barely detectable. However, the expression of other integrins and the levels of mitogen-activated protein kinase hardly changed. On these grounds, we presumed that norcantharidin induced HT-29 colon cancer cell apoptosis through the alphavbeta6-ERK signaling pathway. This finding elicited a novel strategy for targeting the whole alphavbeta6-ERK signal pathway, rather than simply blocking the combining site of alphavbeta6-ERK in colon cancer treatment.
Peng
Cheng
C
Department of General Surgery, QiLu Hospital, Shandong University, Jinan, Shandong, China.
Liu
Xiangqun
X
Liu
Enyu
E
Xu
Kesen
K
Niu
Weibo
W
Chen
Rong
R
Wang
Jiayong
J
Zhang
Zhaoyang
Z
Lin
Pengfei
P
Wang
Jian
J
Agrez
Michael
M
Niu
Jun
J
D000951:Antigens, Neoplasm / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D016023:Integrins / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
D000951:Antigens, Neoplasm; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016023:Integrins; C073878:integrin alphavbeta6; C069741:norcantharidin; D048049:Extracellular Signal-Regulated MAP Kinases