Gene expression pattern in apoptotic QGY-7703 cells induced by homoharringtonine

Abstract

Aim: To classify the genes responsible for apoptosis in QGY-7703 cells induced by homoharringtonine (HHT). Methods: Apoptosis in QGY-7703 cells induced by HHT was demonstrated by DNA fragmentation and morphological observation. cDNA microarray technology was used to detect gene transcription, and the result of microarrays for genes was confirmed by RT-PCR. Results: Seventy-eight individual mRNA were identified and their transcription levels changed significantly. Those genes, of which 68% were upregulated and 32% were downregulated, were partially related to apoptosis. They were mostly oncogenes, tumor suppressors, enzymes, and kinases. Conclusion: HHT is a potential drug in the treatment of liver cancer. TGF-β, TNF, FAS, p38MAPK, and p53 apoptosis signaling pathways were activated during apoptosis in QGY-7703 cells. Such inducible genes may play important roles in apoptosis and deserve to be further studied. Key wordsQ G Y-7 7 0 3 cells; homoha r r i ngtonine; apoptosis; gene expression

Cephalotaxus Alkaloids

“…However, the operating conditions used after the synthesis of the spiro system must be chosen carefully because of the risk of racemization of CET (1) and certain synthetic intermediates by breaking the N9eC5 bond (See Figs. 181 The head protein of intrinsic apoptosis cascade is p53. Last but not least, from an industrial point of view, initially the Merck Group took over the Weinreb racemic synthesis improving performance (11.7% by eliminating some purification steps).…”

“…18 and 19, the conversion of Mori's intermediates (AE)-88 and (À)-88). It was activated by HHT (2) in human hepatoma QGY-7703 cells 181 , but cell line with p53 mutation was more resistant to HHT (2). The optically active CET (1) in its natural configuration may be obtained by resolution of racemic cephalotaxine rac-CET (AE)-(1) with tartaric acid, by incorporation of chiral sources, or by enantioselective synthesis.…”

Protein synthesis inhibitors of natural origin for CML therapy: semisynthetic homoharringtonine (Omacetaxine mepesuccinate)

“…Possibly, this is caused by the inhibition of mRNA expression of corresponding genes, especially of CenpB and other centromere protein genes, as the expression of these genes is related to apoptosis induction by harringtonine. Additionally, it was shown that TgF-beta, TNF, FAS, p38MAPK and p53 apoptosis signaling pathways are activated during homoharringtonine-induced apoptosis in QgY-7703 cells [29]. When tested in myeloma cells, homoharringtonine significantly reduced Mcl-1 -an essential protein for myeloma cell survival [30].…”