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.
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)alpha and RARbeta. 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.


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-IO1 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).


CONCLUSIONS
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.
Inoue
Yuzuru
Y
Department of Surgery 1, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahata-nishi-ku, Kita-kyushu 807-8555, Japan.
Nakayama
Yoshifumi
Y
Sako
Tatsuhiko
T
Minagawa
Noritaka
N
Abe
Yukio
Y
Nagato
Masaru
M
Kadowaki
Koji
K
Katsuki
Takefumi
T
Matsumoto
Kentaro
K
Tsurudome
Yosuke
Y
Shibao
Kazunori
K
Hirata
Keiji
K
Nagata
Naoki
N
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D014297:Trimethylsilyl Compounds / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001565:Benzoates; D047888:Receptors, Tumor Necrosis Factor, Type I; C112689:TAC 101; D014297:Trimethylsilyl Compounds; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9