4-[3,5-Bis(trimethylsilyl)benzamido] Benzoic Acid (TAC-101) Induced Fas Expression and Activated Caspase-3 and -8 in a DLD-1 Colon Cancer Cell Line

• Published in: In vivo (Athens) Vol. 21; no. 2; pp. 381 - 387
• Main Authors: Inoue, Yuzuru, Nakayama, Yoshifumi, Sako, Tatsuhiko, Minagawa, Noritaka, Abe, Yukio, Nagato, Masaru, Kadowaki, Koji, Katsuki, Takefumi, Matsumoto, Kentaro, Tsurudome, Yosuke, Shibao, Kazunori, Hirata, Keiji, Nagata, Naoki
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.03.2007
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Benzoates - pharmacology; Caspase 3 - metabolism; Caspase 8 - metabolism; Caspase 9 - metabolism; Cell Line, Tumor; Colonic Neoplasms; Enzyme Activation - drug effects; Humans; Kinetics; Receptors, Tumor Necrosis Factor, Type I - genetics; Trimethylsilyl Compounds - pharmacology
• ISSN: 0258-851X; 1791-7549

Background: 4-[3,5-Bis (trimethylsilyl) benzamido] benzoic acid (TAC-101) is a novel retinobenzoic acid derivative which has a specific binding affinity to the retinoic acid receptors (RAR)α and RARβ. Using time-dependent FACScan analysis, it was observed that TAC-101 induced apoptosis in a DLD-1 human colon cancer cell line. In this study, the induction of apoptosis-related proteins and the activities of caspases in a DLD-1 cell line under medication with TAC-101 were investigated. Materials and Methods: DLD-1 cells were cultured with different concentrations of TAC-101 for 12, 24 and 48 h. The expressions of Fas, TNF-R1, DR3, bcl-2, Bax and Bid were measured using a Western blot analysis. The activities of caspase-3, -8 and -9 were measured using a colorimetric protease assay kit. Results: The Western blot analysis showed that TAC-101 had almost no effect on the level of Bcl-2, Bax or Bid protein. Although TAC-101 did not change the expression of TNF-R1 and DR3, TAC-101 increased the expression of Fas in both a time- and a dose-dependent manner. A 3-fold increase in caspase-3 activity and a 1.5-fold increase in caspase-8 activity were observed in cells treated with TAC-101 in comparison to the control cells (p<0.01). Conclusion: Our data indicate that the death receptor root of the apoptotic signal transduction in DLD-1 cells mainly participates in the apoptotic induction of TAC-101. Because the compounds inducing apoptotic activity are frequent targets of cancer therapy, TAC-101 may be a good candidate for use in the treatment of colon cancer.