title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Oral TAC-101 shows potential as a novel antitumor agent for ovarian carcinoma, especially ovarian clear cell adenocarcinoma.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan. naos@sc.itc.keio.ac.jp
authors.forename: Nao
authors.initials: N
authors.lastname: Suzuki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.forename: Shinji
authors.initials: S
authors.lastname: Oie
authors.forename: Miwa
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ezawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Susumu
authors.forename: Fumihito
authors.initials: F
authors.lastname: Hosoi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitazato
authors.forename: Shiro
authors.initials: S
authors.lastname: Nozawa
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D014297:Trimethylsilyl Compounds / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D000097768:Retinoic Acid Receptor gamma
chemical_list: D000970:Antineoplastic Agents; D001565:Benzoates; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014297:Trimethylsilyl Compounds; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C000607072:Rara protein, mouse; C112689:TAC 101; C082925:retinoic acid receptor beta