In vivo antitumor efficacy and cardiotoxicity of novel anthracycline ID6105 (11-hydroxy-aclacinomycin X, Hyrubicin).
Hybrid biosynthetic approach produced a new anthracycline ID6105 (11-hydroxyaclacinomycin X, Hyrubicin), which has potent antitumor activities against a broad range of cancer cell lines. Like other anthracyclines, ID6105 has the inhibitory effects on DNA synthesis as well as topoisomerase II. As preclinical studies of ID6105, we investigated ID6105's efficacy on human tumors, and cardiotoxicity. In human tumor xenografts, the ID6105's antitumor effects were greater than other anticancer drugs. ID6105 induced tumor regression in Hep G2 human hepatoma model, and slowed down the tumor growth rates in several tumor models. Doxorubicin-refractory tumors such as PC-3, DU-145, and CX-1 were sensitive to ID6105, and the growth of EKVX, lung cancer, which did not respond to paclitaxel, was also inhibited by ID6105, but tumor mass in CFPA, MCF7, and HCT-15 was not reduced by ID6105. The cardiotoxicity of ID6105 has also been assessed in rats. ID6105 did not induce any remarkable histopathological changes in hearts, and its lipid peroxidation in rat cardiac muscles did not occur as much as doxorubicin, indicating that the cardiotoxicity of ID6105 is remarkably lower than that of doxorubicin. Taking all into account, our results suggest that ID6105 would be a promising candidate for a novel anthracycline chemotherapeutic agent.
Ryu
Jung Su
JS
Laboratory of Microbiology, Il-dong Pharmaceutical Co., Ltd., 260-5, Eonnam-Ri, Kusseong-Eup, Yongin,, Gyongki-Do 449-915, Korea.
Lee
Hong Sub
HS
Hong
Young-Soo
YS
Lee
Jung Joon
JJ
Sohn
Uy Dong
UD
Kim
Tae Yong
TY
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D019384:Nucleic Acid Synthesis Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059005:Topoisomerase II Inhibitors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
C099664:11-hydroxyaclacinomycin X; D000970:Antineoplastic Agents; D019384:Nucleic Acid Synthesis Inhibitors; D059005:Topoisomerase II Inhibitors; D008315:Malondialdehyde; D015250:Aclarubicin; D004317:Doxorubicin