A novel retinoid, 4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid (TAC-101), induces apoptosis of human ovarian carcinoma cells and shows potential as a new antitumor agent for clear cell adenocarcinoma

Nao Suzuki, Daisuke Aoki, Shinji Oie, Miwa Horiuchi, Yuko Hasegawa, Sachiko Ezawa, Atsushi Suzuki, Nobuyuki Susumu, Fumihito Hosoi, Kenji Kitazato, Shiro Nozawa

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Abstract

Objectives. A novel retinobenzoic acid derivative, 4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid (TAC-101), was reported to suppress the growth and invasion of human gastric cancer or hepatocellular carcinoma by induction of apoptosis. We examined the antitumor activity of TAC-101 against human ovarian carcinoma cell lines. Methods. Apoptosis of human epithelial ovarian carcinoma-derived cell lines (RMG-I, RMG-II, RTSG, RMUG-S, RMUG-L, and KF) was investigated by detecting DNA laddering and was quantified by an enzyme-linked immunosorbent assay. Inhibition of apoptosis was also examined using a caspase inhibitor. Furthermore, TAC-101 (8 mg kg-1 day -1 orally for 30 days) was investigated in nude mice with subcutaneous RMG-II tumors. A prominent apoptotic response to TAC-101 was observed. The antitumor effects of cisplatin (7 mg/kg intravenously on day 1) and paclitaxel (36 mg/kg intravenously on days 1 and 5) were also assessed for comparison. Results. Apoptosis occurred in all of the cell lines (except KF) in a concentration-dependent manner after exposure to TAC-101 and was markedly induced in RMG-I and RMG-II cells (derived from ovarian clear cell adenocarcinomas). A caspase inhibitor blocked the induction of apoptosis by TAC-101. The maximum inhibition of RMG-II tumor growth in nude mice by TAC-101, cisplatin, and paclitaxel was 45%, 34%, and 47%, respectively. Conclusion. Oral TAC-101 shows potential as a novel antitumor agent for ovarian carcinoma, especially ovarian clear cell adenocarcinoma.

Original languageEnglish
Pages (from-to)643-649
Number of pages7
JournalGynecologic Oncology
Volume94
Issue number3
DOIs
Publication statusPublished - 2004 Sep 1

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Keywords

  • Apoptosis
  • Clear cell adenocarcinoma
  • Ovarian carcinoma
  • Synthetic retinoid
  • TAC-101

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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