title: Curcumin targets the AKT-mTOR pathway for uterine leiomyosarcoma tumor growth suppression.
abstract: BACKGROUND
  Uterine leiomyosarcomas generally do not respond well to standard chemotherapy. We previously demonstrated that curcumin, the active ingredient derived from the herb Curcuma longa, inhibits uterine leiomyosarcoma cells in vitro via the inhibition of the AKT-mammalian target of rapamycin (mTOR) pathway. As a preclinical investigation, we performed an in vivo study using female nude mice to confirm the therapeutic potential of curcumin against uterine leiomyosarcoma.
  
  
  METHODS
  Human leiomyosarcoma cells, SK-UT-1, were inoculated in female nude mice to establish subcutaneous tumors. Either vehicle control or 250 mg/kg curcumin was administered intraperitoneally every day for 14 consecutive days, and the mice were then killed. The tumors were measured every 2-3 days. The tumors were processed for immunohistochemical analyses to detect total AKT, phosphorylated AKT, total mTOR, phosphorylated mTOR, and phosphorylated S6. To detect apoptosis, the tumors were stained for cleaved PARP and TUNEL. Ki-67 immunohistochemistry was performed to determine cell viability of the tumors.
  
  
  RESULTS
  Compared with the control, curcumin reduced uterine leiomyosarcoma tumor volume and mass significantly with a concordant decrease in mTOR and S6 phosphorylation. However, AKT phosphorylation was not significantly altered. Cleaved PARP and TUNEL staining increased significantly with curcumin administration, indicating the induction of apoptosis. There was no difference in Ki-67 staining between the two groups.
  
  
  CONCLUSIONS
  Curcumin inhibited uterine leiomyosarcoma tumor growth in vivo by targeting the AKT-mTOR pathway for inhibition.
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Tze Fang
authors.initials: TF
authors.lastname: Wong
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeda
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsuiji
authors.forename: Akiko
authors.initials: A
authors.lastname: Kondo
authors.forename: Mari
authors.initials: M
authors.lastname: Tadakawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagase
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D003474:Curcumin