Inhibitory Effect Of Ornithine Decarboxylase And S-adenosylmethionine Decarboxylase Biantisense Adenovirus-Mediated Polyamine Depletion On Colorectal Cancer

Polyamines are naturally aliphatic polycations found in almost all living species. Polyamines include spermidine, spermine and their diamine precursor, putrescine. At physiological pH value, polyamines carry a positive charge on each nitrogen atom, which facilitates their interaction with polyanion molecules such as DNA and RNA. Polyamines have important physiological functions. They are critical for cell growth and differentiation. In mammalian cells intracellular polyamine biosynthetic pathway is mainly regulated by the action of two rate-limiting enzymes. Ornithine decarboxylase (ODC) is the first key enzyme required for polyamine synthesis. It catalyzed ornithine decarboxylation to produce putrescine. The second rate-limiting enzyme is S-adenosylmethionine decarboxylase (AdoMetDC). It functions to generate the aminopropyl donor, dcSAM, by decarboxylasing adenosylmethionine. DcSAM donates its propylamine moiety to form spermidine and spermine catalyzed by spermidine synthase and spermine synthase, respectively. In addition, exogenous polyamines can also be imported into cells through a transport mechanism that is not clearly defined .Polyamine not only plays a key role in metabolism of normal cells but also correlates with tumorigenesis. In cancer cells and tissues polyamine levels and polyamine biosynthesis are highly elevated. ODC and AdoMetDC in normal cells were also activated by many chemical carcinogens and tumor promoters such asv-src, neu and Ras. Therefore, polyamine biosynthesis pathway becomes an important target...