Apoptosis induced by ID6105, a new anthracycline (11-hydroxyaclacinomycin X, Hyrubicin), and its anti-tumor effects on experimental tumor models.
A new anthracycline ID6105 (11-hydroxyaclacinomycin X, Hyrubicin), which has potent antitumor activities against a broad range of cancer cell lines, was produced by hybrid biosynthetic approach. We investigated ID6105-induced apoptosis and in vivo efficacy on experimental tumors, and also defined its optimal dosing schedule. From PARP cleavage assay and caspase-3 activation assay, we found that ID6105 can induce apoptosis in tumor cells and its ability was superior to doxorubicin. In human tumor xenograft models, ID6105 showed greater antitumor effects on SW620 and NCI-H23 than doxorubicin. The 1 mg/kg of ID6105 treatment reduced size of tumor by 93% in NCI-H23 model whereas doxorubicin (2 mg/kg) showed only 39% inhibition rate. In SW620 model, 0.3 mg/kg of ID6105 proved to be comparable to 2 mg/kg of doxorubicin. Testing with several dosing schedule such as qd10, qd5, and q4d3, we decided intravenous qd5 treatment was an optimal schedule as a dose regimen of ID6105. In conclusion, ID6105 is a potent apoptosis-inducing anthracycline and effective in treatment of tumors with qd5 dosing schedule.
Lee
Hong Sub
HS
Research Laboratories, IlDong Pharmaceutical Co., Ltd., Gyongki, South Korea.
Ryu
Jung Su
JS
Jeon
Yong-Jin
YJ
Hong
Young-Soo
YS
Lee
Jung Joon
JJ
Hong
Soon-Kwang
SK
Kim
Tae-Yong
TY
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D023041:Xenograft Model Antitumor Assays
C099664:11-hydroxyaclacinomycin X; D000970:Antineoplastic Agents; D015250:Aclarubicin; D004317:Doxorubicin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3