[Antitumor effect of a novel antitumor compound, NC-190, in the double grafted tumor system].

Abstract

The antitumor effect of NC-190, N-beta-dimethylaminoethyl-9-carboxy-5-hydroxy-10-methoxybenzo [alpha] phenazine-6-carboxamide sodium salt, with a new experimental mouse model was studied. Intratumoral administration of NC-190 strongly inhibited the growth of Meth-A solid tumors in male BALB/c mice and led to a complete tumor regression and also resistance to the reinoculated tumor. Subsequently, the anti-metastatic effect of NC-190 was examined in the double grafted tumor system, in which mice first received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with 25 micrograms of NC-190 in the right tumor on days 3, 4 and 5. NC-190 inhibited the growth of not only the right but also the left, non-treated tumor. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of NC-190. Adoptive transfer of NC-190 immunized spleen cells caused a complete regression of Meth-A tumors. The effector cell activity was lost only after treatment with anti-Lyt-2 antibody. These results suggest that intratumoral administration of NC-190 might induce Lyt-2 positive cytotoxic cells in the spleen and the left, non-treated tumor. In BALB/c nude mice, NC-190 inhibited slightly the growth of the right tumor but did not that of the left tumor. Therefore, the antitumor activity of NC-190 in the double grafted tumor system was judged as associated with a sequential immune mechanism in which T cells may play an important role. TILs (tumor infiltrating lymphocytes) obtained from the left and right sides tumors treated with NC-190 were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TILs obtained from neither sides inhibited the growth of admixed Meth-A cells. Different from immunopotentiators such PSK or IL-1, NC-190 enhanced neither concomitant immunity nor sinecomitant immunity.

• Authors: T Ebina, K Shishido, K Murata
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 17 Issue 7 Pg. 1345-50 (Jul 1990) ISSN: 0385-0684 [Print] Japan
• PMID: 2369138 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Phenazines
• NC 190

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Immunization, Passive
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation (methods)
• Phenazines (therapeutic use)
• Sarcoma, Experimental (drug therapy, immunology, pathology)
• T-Lymphocytes (immunology)