Inhibition of anchorage-independent growth of tumor cells by IT-62-B, a new anthracycline.
IT-62-B, a new anthracycline isolated from fermentation broths of Streptomyces sp. IT-62, reversed certain tumor cell phenotypes in vitro including some of human origin. The observed normal phenotypes were anchorage dependence of cell growth, flattened cell morphology and restoration of actin stress fibers. The extent of the anchorage dependence of cell growth induced by IT-62-B was generally greater than that by doxorubicin or pirarubicin. The cell-flattening effect of IT-62-B on cells of T24 (human bladder), but not on C-33A (human cervix), accompanied inhibition of fos gene expression. T24 cells, once flattened by IT-62-B, retained their flat morphology even in drug-free, fresh medium and eventually died in several days. IT-62-B, unlike doxorubicin, only slightly inhibited the topoisomerase II reaction in vitro and DNA synthesis in isolated cell nuclei.
Tsuchiya
K S
KS
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Ishii
T
T
Ikeno
S
S
Kunimoto
S
S
Kawauchi
T
T
Otani
T
T
Hori
M
M
D000199:Actins / Q000378:metabolism; D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016762:Genes, fos; D011905:Genes, ras; D006801:Humans; D051379:Mice; D009154:Mutation; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000199:Actins; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; C106747:IT 62-B; D004317:Doxorubicin; C027260:pirarubicin; D004250:DNA Topoisomerases, Type II