A NOVEL ANTITUMOR CYCLIC HEXAPEPTIDE (RA-700) OBTAINED FROM RUBIAE RADIX
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概要
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The antitumor activity of a newly obtained cyclic hexapeptide, RA-700,from Rubiae Radix was studied using several murine experimental tumor systems. In P388 leukemia (inoculated intraperitoneally (i.p.), administered i.p. : i.p.-i.p.) the maximal increase in life span (ILS_<max>) resulting from an administration of RA-700 (4 mg/kg/d for 9 d) was 134% and the therapeutic ratio was 400. These values indicate that RA-700 has higher antitumor activity and broader active dose range than that of mitomycin C (MMC, 1 mg/kg/d for 9 d) which was used as a positive control. In the study of the treatment schedules on P388,RA-700 had the highest activity by consecutive injections. In MOPC-104E mouse plasmacytoma system (i.p.-i.p.), ILS_<max> of RA-700 (2.5 mg/kg/d for 9 d) was 84%. In a solid tumor, colon adenocarcinoma 38 (subcutaneously (s.c.)-intravenously (i.v.)), RA-700 (4 mg/kg/d for 11 d) showed complete cures (8/8) compared to MMC (0.5 mg/kg/d for 11 d) which showed one cure out of 8 animals. In the study of a model of the inhibition of lymph node metastasis using P388 leukemia, the administration of RA-700 at more than 2.5 mg/kg/d i.v. for 7 d resulted in the survival of all animals (5/5) for over 60 d. In the amputation system of the same metastasis model at a dose of 4 mg/kg/d i.v. for 7 d, 3 animals out of 5 survived over 60 d. With regard to spontaneous metastasis using a highly metastatic B16 melanoma, B16-BL6,RA-700 (4 mg/kg/d i.v. for 11 d) showed 97% inhibition of the number of pulmonary nodules compared to the control and this activity was similar to that shown by doxorubicin (2.5 mg/kg i.v. for 11 d). Thus, RA-700 was considered a good candidate of a new type of antitumor agent.
- 公益社団法人日本薬学会の論文
著者
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Tsuruo Takashi
Division Of Molecular Oncology Aichi Cancer Center Research Institute
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Tsuruo Takashi
The Cancer Chemotherapy Center Japanese Foundation For Cancer Research (jfcr)
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Kawahara Kazuo
Ome Research Laboratories Tobishi Pharmaceutical Co. Ltd.:cancer Chemotherapy Center Japanese Founda
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Tsuruo T
The Cancer Chemotherapy Center Japanese Foundation For Cancer Research (jfcr)
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Yamakawa Kenji
Ome Research Laboratories Tobishi Pharmaceutical Co. Ltd.:cancer Chemotherapy Center Japanese Founda
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HAMANAKA TOSHINORI
Ome Research Laboratories, Tobishi Pharmaceutical Co., Ltd.
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OHGOSHI MIKIKO
Ome Research Laboratories, Tobishi Pharmaceutical Co., Ltd.
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TSURUO TAKASHI
Ome Research Laboratories, Tobishi Pharmaceutical Co., Ltd.
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TSUKAGOSHI SHIGERU
Ome Research Laboratories, Tobishi Pharmaceutical Co., Ltd.
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Ohgoshi Mikiko
Ome Research Laboratories Tobishi Pharmaceutical Co. Ltd.:cancer Chemotherapy Center Japanese Founda
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Tsukagoshi S
Japanese Foundation For Cancer Res. Tokyo
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Tsuruo T
Japanese Foundation For Cancer Research Tokyo Jpn
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Hamanaka Toshinori
Ome Research Laboratories Tobishi Pharmaceutical Co. Ltd.:cancer Chemotherapy Center Japanese Founda
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Taniguchi Tetsuo
The Cancer Chemotherapy Center, Japanese Foundation for Cancer Research (JFCR)
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