An inhibitor of translation
Harringtonine is a protein synthesis inhibitor [1].
Harringtonine, homoharringtonine and isoharringtonine are alkaloids from Cephalotaxus harringtonia. They have an antitumour activity due to their inhibitory effect on protein synthesis and differ only in a side chain [1].
Harringtonine is a natural alkaloid from Cephalotaxus harringtonia that inhibits protein synthesis in eukaryotic cells. Harringtonine inhibit the initiation of polypeptide synthesis. Harringtonine blocks peptide bond formation and aminoacyl-tRNA binding [1][2]. Harringtonine also immobilizes ribosomes immediately after translation initiation, which can be used to capture ribosome-protected mRNA fragments for evaluating translation [2]. The homolog of harringtonine, homoharrington inhibited the first steps of elongation and rapidly degraded short-lived proteins. In Pten+/- Eμ-Myc lymphomas, homoharrington blocked translation and reduced levels of Mcl-1, Cyclin D1, and c-Myc.
In mice with BCR-ABL-induced CML, homoharrington (also known as omacetaxine) significantly reduced the numbers of both LSCs and total leukemia cells [3][4].
参考文献:
[1].? Fresno M, Jiménez A, Vázquez D. Inhibition of translation in eukaryotic systems by harringtonine. Eur J Biochem. 1977 Jan;72(2):323-30.
[2].? Ingolia NT, Brar GA, Rouskin S, et al. The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. Nat Protoc. 2012 Jul 26;7(8):1534-50.
[3].? Kantarjian HM, O'Brien S, Anderlini P, et al. Treatment of myelogenous leukemia: current status and investigational options. Blood. 1996 Apr 15;87(8):3069-81.
[4].? Chen Y, Peng C, Sullivan C, et al. Novel therapeutic agents against cancer stem cells of chronic myeloid leukemia. Anticancer Agents Med Chem. 2010 Feb;10(2):111-5.
Cell experiment: | For harringtonine treatment studies with Sindbis virus, BHK21 cells are seeded into 96-well plates and infected with Sindbis virus at an MOI of 1 for 1 h prior to being washed twice with PBS and incubated with various concentrations of harringtonine (0.1 μM, 1 μM, 5 μM, and 10 μM) at 37°C with 5% CO2. Cell supernatants are harvested for plaque assays at 24 h postinfection[2]. |
参考文献: [1]. Fresno M, et al. Inhibition of translation in eukaryotic systems by harringtonine. Eur J Biochem. 1977 Jan;72(2):323-30. | |
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