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A synthetic retinoid, TAC-101 (4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid), plus cisplatin: potential new therapy for ovarian clear cell adenocarcinoma.

AbstractOBJECTIVE:
A novel retinoid, TAC-101 (4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid), induces apoptosis of ovarian clear cell adenocarcinoma. The antitumor effect of TAC-101 alone or combined with cisplatin was tested using human ovarian carcinoma.
METHODS:
Induction of genes related to apoptosis by TAC-101 or cisplatin was assessed by DNA microarray analysis. TAC-101 (8 mg/kg/day orally for 21 days), cisplatin (7 mg/kg intravenously on day 1), or a combination of both drugs at the same dosages was administered to nude mice implanted subcutaneously with RMG-I or RMG-II clear cell adenocarcinoma cells. The antitumor effect was evaluated by calculating the treated/control tumor volume ratio at 21 days after implantation. The histoculture drug response assay was also performed using fresh surgical specimens of human ovarian cancer to determine the 50% inhibitory concentration (IC50).
RESULTS:
Different apoptosis-related genes were induced by TAC-101 and cisplatin. Compared with control mice, the volume of both RMG-I and RMG-II tumors was significantly reduced (p<0.05) by either drug. The IC50 values of cisplatin and TAC-101 showed a significant correlation (p<0.01).
CONCLUSION:
These in vitro findings suggest that a combination of TAC-101 and cisplatin may be a potential new treatment for ovarian clear cell adenocarcinoma.
AuthorsSachiko Ezawa, Nao Suzuki, Shinji Ohie, Atsushi Higashiguchi, Fumihito Hosoi, Kenji Kitazato, Nobuyuki Susumu, Daisuke Aoki
JournalGynecologic oncology (Gynecol Oncol) Vol. 108 Issue 3 Pg. 627-31 (Mar 2008) ISSN: 1095-6859 [Electronic] United States
PMID18048092 (Publication Type: Journal Article)
Chemical References
  • Benzoates
  • TAC 101
  • Trimethylsilyl Compounds
  • Cisplatin
Topics
  • Adenocarcinoma, Clear Cell (drug therapy, pathology)
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Apoptosis (drug effects)
  • Benzoates (administration & dosage, pharmacology)
  • Cell Line, Tumor (drug effects)
  • Cisplatin (administration & dosage, pharmacology)
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms (drug therapy, pathology)
  • Trimethylsilyl Compounds (administration & dosage, pharmacology)

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