Tumor-specific cytotoxic activity of 1,2,3,4-tetrahydroisoquinoline derivatives against human oral squamous cell carcinoma cell lines.
The tumor-specific cytotoxicity and the type of cell death induced by thirty-eight newly synthesized tetrahydroisoquinoline derivatives in human oral squamous cell carcinoma cell lines were investigated. 6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)(3,4-dimethoxyphenyl) methanone that has bulky substituents (such as 3,4-dimethoxybenzoyl group) (TQ9) and ethyl 2-benzyloxycarbonyl-1,2,3,4-tetrahydroisoquinoline-1-carboxylate that has ethoxycarbonyl group and benzyloxycarbonyl group (TD13) showed the highest tumor-specific cytotoxicity (TS=12.5 and 5.3, respectively). This supports the importance of molecular size for the cytotoxicity induction. TQ9 induced internulceosomal DNA fragmentation and caspase-3 activation only marginally in HL-60 cells, whereas it enhanced the formation of acidic organelles (stained with acridine orange) without induction of DNA fragmentation or caspase-3 activation in human squamous cell carcinoma cell lines (HSC-2, HSC-4), suggesting the induction of autophagy in the latter cells.
Hatano
Hajime
H
Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Takekawa
Fumihiro
F
Hashimoto
Ken
K
Ishihara
Mariko
M
Kawase
Masami
M
Qing
Chu
C
Qin-Tao
Wang
W
Sakagami
Hiroshi
H
D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D015388:Organelles / Q000187:drug effects; D044005:Tetrahydroisoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline; D053148:Caspase 3