title: Norcantharidin Inhibits cell growth by suppressing the expression and phosphorylation of both EGFR and c-Met in human colon cancer cells.
abstract: Norcantharidin (NCTD) is a Chinese FDA approved, chemically synthesized drug for cancer treatment. The effect of NCTD on signaling proteins of EGFR and c-Met was systematically elucidated in current study.
  
  
  
  Two human colon cancer cell lines, HCT116 and HT29, were used as model systems to investigate the anti-cancer molecular mechanism of NCTD. Cell cycle arrest and early/late apoptosis were analyzed by flow cytometry. The levels of EGFR, phospho-EGFR, c-Met, phospho-c-Met and other related proteins were quantified by western blot analysis.
  
  
  
  NCTD induced cell cycle arrest at G2/M phase in both cell lines. The early and late apoptosis was also observed. Further investigation indicated that NCTD suppressed not only the expression of the total EGFR and the phosphorylated EGFR but also the expression of the total c-Met and the phosphorylated c-Met in colon cancer cells. Moreover, EGFR expression could be mostly restored by co-treatment with MG132, a proteasome inhibitor. In addition, NCTD-induced cell death was comparable to that of the anti-cancer drug gefitinib, a tyrosine kinase inhibitor for EGFR, based on the immunoblot analysis of the expressed proteins after the drug treatment.
  
  
  
  NCTD might be a useful and inexpensive drug candidate to substitute for gefitinib to serve the treatment needs of cancer patients.
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Peiju
authors.initials: P
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Siwen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: He
authors.initials: H
authors.lastname: Ma
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Yidi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: He
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China. lijuanzhang@ouc.edu.cn.|Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Qingdao, 266003, China. lijuanzhang@ouc.edu.cn.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D000077156:Gefitinib; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011799:Quinazolines; C069741:norcantharidin; C512478:EGFR protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D000077156:Gefitinib
keywords: Apoptosis; Cell cycle; Colon cancer; EGFR; Norcantharidin; c-Met