title: Epigallocatechin-3-gallate potentiates curcumin's ability to suppress uterine leiomyosarcoma cell growth and induce apoptosis.
abstract: BACKGROUND
  Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapeutic regimens. Two natural occurring compounds, curcumin and epigallocatechin gallate (EGCG), are reported to have anti-cancer activity. We previously reported that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway. However, challenges remain in overcoming curcumin's low bioavailability.
  
  
  METHODS
  The human LMS cell line SKN was used. The effect of EGCG, curcumin or their combination on cell growth was detected by MTS assay. Their effect on AKT, mTOR, and S6 was detected by Western blotting. The induction of apoptosis was determined by Western blotting using cleaved-PARP specific antibody, caspase-3 activity and TUNEL assay. Intracellular curcumin level was determined by a spectrophotometric method. Antibody against EGCG cell surface receptor, 67-kDa laminin receptor (67LR), was used to investigate the role of the receptor in curcumin's increased potency by EGCG.
  
  
  RESULTS
  In this study, we showed that the combination of EGCG and curcumin significantly reduced SKN cell proliferation more than either drug alone. The combination inhibited AKT, mTOR, and S6 phosphorylation, and induced apoptosis at a much lower curcumin concentration than previously reported. EGCG enhanced the incorporation of curcumin. 67LR antibody partially rescued cell proliferation suppression by the combination treatment, but was not involved in the EGCG-enhanced intracellular incorporation of curcumin.
  
  
  CONCLUSIONS
  EGCG significantly lowered the concentration of curcumin required to inhibit the AKT-mTOR pathway, reduce cell proliferation and induce apoptosis in uterine LMS cells by enhancing intracellular incorporation of curcumin, but the process was independent of 67LR.
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Seiryomachi 1-1, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kondo
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: Mari
authors.initials: M
authors.lastname: Kitamura
authors.forename: Tze Fang
authors.initials: TF
authors.lastname: Wong
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
mesh_terms: D017209:Apoptosis; D001682:Biological Availability; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000096:biosynthesis; D017474:Receptors, Laminin / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000096:biosynthesis; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D017474:Receptors, Laminin; D002392:Catechin; C045651:epigallocatechin gallate; C546842:MTOR protein, human; D051058:Oncogene Protein v-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D003474:Curcumin