%0 Journal Article
%T DRF 3188 a novel semi-synthetic analog of andrographolide: cellular response to MCF 7 breast cancer cells
%A Chitkala Satyanarayana
%A Dhanavanthri S Deevi
%A R Rajagopalan
%A Nanduri Srinivas
%A Sriram Rajagopal
%J BMC Cancer
%D 2004
%I BioMed Central
%R 10.1186/1471-2407-4-26
%X The effect of the compounds on cell cycle was determined using FACS and western blot analysis of cell cycle proteins. Hollow fibre assay was used to determine if the compounds had the same effect on the cell cycle in vitro and in vivo.Our results from the in vitro and in vivo experiments show that both the compounds block the cell cycle at the G0-G1 phase through the induction of the cell cycle inhibitor, p27, and the concomitant decrease in the levels of Cdk4.The results show that the novel semi-synthetic analog, DRF3188, and andrographolide bring about the anti cancer activity by a similar mechanism.Cell cycle can be defined as an ordered set of events culminating in cell growth and division into two identical daughter cells. In normal cells this complex process is initiated only in the presence of a mitogenic stimulus. Various proteins like the cyclin dependent kinases; cyclins and cyclin dependent kinase inhibitors regulate this event [1]. However, in cancer cells this regulation of the cell cycle is lost and the cells continue to divide irrespective of the presence or absence of a mitogenic stimulus [2]. This observation has led to deciphering the mechanism of action of many of the known anti-cancer agents, currently in clinical use. These agents were shown to block the cell cycle at different stages. Examples include, Methotrexate (blocks at the S-phase), Doxurubicin (blocks at the G2 phase), Topotecan (blocks at the S and G2 phase) etc. Intense research efforts are now on for identifying cell cycle specific inhibitors for the treatment of cancer (Ex: Flavopiridol).Andrographolides, obtained from the herb Andrographis paniculata, are known to have several medicinal properties including anti-cancer activity [3-6]. Using andrographolide (Fig. 1) as a template a library of analogs were synthesized and analysed for anti-cancer activity. One of the semi-synthetic analogs, DRF 3188 (Fig. 1), [7] was shown to have a better anti-cancer activity compared to the parent
%K Andrographolide
%K Semi-synthetic analog
%K cell cycle
%K Hollow fibre assay
%U http://www.biomedcentral.com/1471-2407/4/26