title: Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation.
abstract: OBJECTIVE
  To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration.
  
  
  METHODS
  Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control.
  
  
  RESULTS
  Our results showed that 20 μmol/L TQ significantly reduced human LoVo colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3K, p-Akt, p-GSK3β, and β-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of β-catenin in LoVo cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoVo cell migration. The results were further verifiedin vivoby confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice.
  
  
  CONCLUSIONS
  TQ inhibits LoVo cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.
authors.affiliation: Hsi-Hsien Hsu, Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Hsi-Hsien Hsu, Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Hsi-Hsien Hsu, Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors.forename: Cecilia Hsuan
authors.initials: CH
authors.lastname: Day
authors.affiliation: Hsi-Hsien Hsu, Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Hsi-Hsien Hsu, Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors.forename: Shin-Yi
authors.initials: SY
authors.lastname: Li
authors.affiliation: Hsi-Hsien Hsu, Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors.forename: Chuan-Chou
authors.initials: CC
authors.lastname: Tu
authors.affiliation: Hsi-Hsien Hsu, Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors.forename: Viswanadha Vijaya
authors.initials: VV
authors.lastname: Padma
authors.affiliation: Hsi-Hsien Hsu, Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors.forename: Hui-Nung
authors.initials: HN
authors.lastname: Shih
authors.affiliation: Hsi-Hsien Hsu, Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: Hsi-Hsien Hsu, Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016227:Benzoquinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D064209:Phytochemicals / Q000627:therapeutic use; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D064209:Phytochemicals; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone; C003466:thymoquinone
keywords: Cyclooxygenase 2; LoVo cell; Migration; Prostaglandin E2; Thymoquinone