title: Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo.
abstract: The antineoplastic effects of combinations of anticancer drugs (5-fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST-8 (2-(2-methoxy- 4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES-2 cells) by combinational use of 5-fluorouracil. JAE and 5-fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES-2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES-2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5-fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5-fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5-fluorouracil and JAE were less than those in mice treated with 5-fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5-fluorouracil on esophageal cancer.
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yamai
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Sawada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yoshida
authors.forename: Jyunichi
authors.initials: J
authors.lastname: Seike
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takizawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kenzaki
authors.forename: Takanori
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kondo
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Bando
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Akira
authors.initials: A
authors.lastname: Tangoku
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004347:Drug Interactions; D004357:Drug Synergism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D000077146:Irinotecan; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D028321:Plant Preparations / Q000494:pharmacology; D027861:Prunus / Q000737:chemistry; D014315:Triterpenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D028321:Plant Preparations; D014315:Triterpenes; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin