Phenoxazine derivative, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one suppresses growth of human retinoblastoma cell line Y79 in vitro and in vivo.
The aim of the study was to evaluate the in vitro and in vivo antitumor effects of the 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-1) on the human retinoblastoma cell line Y79. The in vitro effects of Phx-1 on cell viability and apoptosis of the human retinoblastoma Y79 cells, were studied by using colorimetric and flow-cytometric methods. The in vivo antitumor effects of Phx-1 on the human retinoblastoma Y79 cells subcutaneously transplanted in BALB/c nude mice were studied, examining the tumor size, the adverse effects on the mice and the histopathological evaluations including hematoxylin and eosin and immunohistochemical staining in the mass of tumors of human retinoblastoma Y79 cells isolated from the mice. Phx-1 suppressed the viability of Y79 cells dose- and time-dependently and induced apoptosis in Y79 cells in vitro. Phx-1 markedly reduced the growth of Y79 cells transplanted into the mice without causing bodyweight loss. Pathological findings of the tumor mass isolated from mice revealed that the tumor of Y79 cells treated with Phx-1 had a decreased mitotic index, decreased expression of Ki67 and p53, no alteration of bcl-2 level and increased caspase-3 activity compared with the the control. Present results suggested that Phx-1 demonstrated antitumor activity against the human retinoblastoma Y79 cells in vitro and in vivo, by inhibiting cell growth and inducing apoptosis. In addition, Phx-1 exerted few adverse side effects on the mice. Phx-1 may be a useful antitumor drug in the treatment of retinoblastoma, which is the most common and serious intraocular malignant tumor.
Kimura
Keisuke
K
Department of Ophthalmology, Tokyo Medical University, Tokyo 160-0023, Japan.
Usui
Yoshihiko
Y
Hattori
Takaaki
T
Yamakawa
Naohiko
N
Goto
Hiroshi
H
Usui
Masahiko
M
Okada
Shinya
S
Shirato
Ken
K
Tomoda
Akio
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010078:Oxazines / Q000494:pharmacology*; D012175:Retinoblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D010078:Oxazines; C039203:phenoxazine