Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo.
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.
Yamai
Hiromichi
H
Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan.
Sawada
Naruhiko
N
Yoshida
Takahiro
T
Seike
Jyunichi
J
Takizawa
Hiromitsu
H
Kenzaki
Koichiro
K
Miyoshi
Takanori
T
Kondo
Kazuya
K
Bando
Yoshimi
Y
Ohnishi
Yoshinari
Y
Tangoku
Akira
A
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
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D028321:Plant Preparations; D014315:Triterpenes; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin