Kinamycin F downregulates cyclin D3 in human leukemia K562 cells.
The bacterial metabolite kinamycin F, which contains an unusual and potentially reactive diazo group, is being investigated as an antitumor agent with a potentially novel target. Treatment of K562 cells with kinamycin F induced erythroid differentiation, a rapid apoptotic response, induction of caspase-3/7 activities and a delayed cell cycle progression through the S and G(2)/M phases. Kinamycin F caused a selective reduction of cyclin D3 protein, which appeared to be mediated at the level of transcription, rather than by affecting the stability of either cyclin D3 protein or mRNA. Thus cyclin D3 is a potential target of kinamycin F.
O'Hara
Kimberley A
KA
Faculty of Pharmacy, Apotex Centre, University of Manitoba, 750 McDermot Ave., Winnipeg, Manitoba R3E 0T5, Canada.
Dmitrienko
Gary I
GI
Hasinoff
Brian B
BB
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D016195:G2 Phase; D006801:Humans; D020014:K562 Cells; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology; D016196:S Phase; D000095602:Angucyclines and Angucyclinones
D000970:Antineoplastic Agents; D053148:Caspase 3; D053179:Caspase 7; D056743:Cyclin D3; D011809:Quinones; C059021:kinamycin F; D000095602:Angucyclines and Angucyclinones