In a sense, cancer chemotherapy is similar to antibacterial chemotherapy. The main target for both chemotherapies is on DNA and its precursors. Whenever anticancer drugs exhibit its activity on cancer cells, damage or metabolic abnormality of DNA is usually accompanied. Among various anticancer drugs, the main cellular target of alkylating agents or anticancer antibiotics is DNA strand, and many of newly introduced anticancer drugs exert effect on DNA strand or DNA synthesis. The mechanism of action of quinocarmycin, KT 6149, which is a derivative of mitomycin C, YM534, which shows thrombocyte agglutination activity, and MCNU, a nitrosourea, were studied for their antitumor action and damage to DNA strand. It was found that there was a close relationship between anticancer effect and single strand scission of DNA in all the agents tested.

01 Dec 1989·The science reports of the research institutes, Tohoku University. Ser. C, Medicine. Tohoku Daigaku

Damage to DNA strand and the effects of anticancer drugs.

Article

Author: Ishikawa, A ; Wakui, A ; Kanamaru, R ; Shibata, H ; Konishi, Y ; Ishioka, C

Cancer chemotherapy is, in a sense, similar to the treatment of infectious disease with antibiotics. The main mechanism of action is on DNA and its precursor, and in the process that anticancer drugs exert the effect on cancer cells, the cells always have abnormal metabolism or destruction of DNA. The main cellular target of most alkylating agents, or anticancer antibiotics is DNA, however, among the anticancer drug newly synthesized, there are some compounds which exert the action on DNA. Quinocarmycin, KT6149, which is a derivative of MMC, YM534, which possesses a platelet agglutinating activity, and MCNU, a nitrosourea compound were studied on the anticancer activity and on damage to DNA strand, and it was found that the lethal effect was deeply concerned with single strand scission of DNA.

01 Aug 1989·Anti-cancer drug design

Mechanism of action of the synthetic imidazole compound YM 534 on human promyelocytic leukemia line HL-60 cells.

Article

Author: Kanamaru, R ; Ishikawa, A ; Wakui, A ; Shibata, H ; Konishi, Y ; Ishioka, C

The effects of a novel anti-cancer drug, YM 534 on human promyelocytic leukemia line HL-60 cells were investigated. The growth of the cells was completely inhibited with an IC50 of 2.5 X 10(-6) M. The incorporation of 3H-thymidine or 3H-uridine into acid insoluble fraction of the cells was completely inhibited at a 10(-4) M concentration of the drug. However, that of 3H-leucine was suppressed by only 32% at this drug concentration. The single strand scission of DNA of the cells as revealed by alkali sucrose density gradient centrifugation was induced by YM 534 at a 10(-4)M concentration for 60 min. When PM2 DNA in a cell-free system was examined in the presence or absence of reducing agent, no damage to DNA was observed at a 10(-4)M YM 534. The processing of preribosomal to ribosomal RNA of HL-60 cells was retarded at a 10(-5) M level of the drug.

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Indication	Highest Phase	Country/Location	Organization	Date
Lymphoma	Phase 1	-	Astellas Pharma, Inc.	-

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