Cytotoxicity of smancs in comparison with other anticancer agents against various cells in culture.
The cytoxicity of neocarzinostatin (NCS) and smancs [copoly(styrene maleic acid)-conjugated NCS] to various cultured cells was compared with that of several other antitumor agens in clinical use on various malignant and non-malignant cells as regards to their effect on colony formation of cells. Both NCS and smancs showed the most potent cytotoxicity against all tumor cell lines tested; the IC50s (colony inhibitory concentration 50%) of these drugs were 3.2-20 nM, 10-1000 times lower than those of other drugs. In contrast, NCS and smancs exhibited relatively lower toxicity to normal cells such as human skin fibroblasts and chick embryonic fibroblasts (IC50, about 50 and 100 nM, respectively). Normal rat hepatocytes were found to be very resistant to NCS and smancs (both IC50s were about 500 nM). Moreover, the minimum exposure time of smancs to cultured tumor cells required to achieve effective cytotoxic activity was much shorter than that of NCS and other drugs. Namely, at 30 nM more than 80% cells were killed by exposure to smancs for only a few minutes, whereas with NCS more than 80 min of exposure time was required. It was also found that smancs inhibited the uptake of 3H-thymidine into DNA as expected. These results clearly indicate that smancs is an unique antitumor agent with a broad antitumor spectrum which exhibits some characteristics similar to, but also some very different from NCS.
Oda
T
T
Department of Microbiology, Kumamoto University School of Medicine, Japan.
Sato
F
F
Yamamoto
H
H
Akagi
M
M
Maeda
H
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008299:Maleic Anhydrides / Q000633:toxicity*; D051379:Mice; D011137:Polystyrenes / Q000633:toxicity*; D009353:Zinostatin / Q000031:analogs & derivatives / Q000633:toxicity*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D005663:Furans; D008299:Maleic Anhydrides; D011137:Polystyrenes; C035755:poly(maleic acid-styrene)neocarzinostatin; D004247:DNA; D009353:Zinostatin