Rhodacyanine dye MKT-077 inhibits in vitro telomerase assay but has no detectable effects on telomerase activity in vivo.
MKT-077, a cationic rhodacyanine dye analogue, causes selective toxicity to cancer cells. Its cellular targets elucidated thus far include oncogenic Ras, F-actin, mortalin (hmot-2)/mthsp70, and telomerase. Here we report that MKT-077 causes growth arrest of cancer cells in culture independent of their Ras, p53, or telomerase status. Telomerase activity is inhibited in vitro by MKT-077 in the telomerase assay used. However, the in vivo toxicity seen in telomerase-positive cancer cells was not accompanied by inhibition of telomerase activity or telomere shortening. Furthermore, cells with an alternative mechanism for lengthening of telomeres were also sensitive to MKT-077 and showed enhanced formation of alternative mechanism for lengthening of telomeres-associated PML bodies in their nuclei. The data suggested that inhibition of telomerase activity is unlikely to be a prime cause of MKT-077-induced toxicity in cancer cells.
Wadhwa
Renu
R
Gene Discovery Research Center, National Institute of Advanced Industrial Science and Technology, Ibaraki 305-8566, Japan.
Colgin
Lorel
L
Yaguchi
Tomoko
T
Taira
Kazunari
K
Reddel
Roger R
RR
Kaul
Sunil C
SC
D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D004396:Coloring Agents / Q000494:pharmacology* / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000633:toxicity; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D024101:Mitochondrial Proteins; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology* / Q000633:toxicity; D019098:Telomerase / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016615:Telomere / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology* / Q000633:toxicity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D004396:Coloring Agents; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; D024101:Mitochondrial Proteins; D011725:Pyridines; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; C080352:mortalin; C097880:MKT 077; D019098:Telomerase; D018631:ras Proteins