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Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo
Author(s) -
Yamai Hiromichi,
Sawada Naruhiko,
Yoshida Takahiro,
Seike Jyunichi,
Takizawa Hiromitsu,
Kenzaki Koichiro,
Miyoshi Takanori,
Kondo Kazuya,
Bando Yoshimi,
Ohnishi Yoshinari,
Tangoku Akira
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24433
Subject(s) - in vivo , fluorouracil , pharmacology , medicine , lewis lung carcinoma , betulinic acid , metastasis , cancer research , cancer , biology , microbiology and biotechnology , genetics
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)‐2 H ‐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‐2cells) 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. © 2009 UICC