Abstract
BackgroundWe determined the effect of andrographolide and one of its novel semi-synthetic analog, DRF 3188, on the cell cycle of MCF 7 breast cancer cells.MethodsThe 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.ResultsOur 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.ConclusionThe results show that the novel semi-synthetic analog, DRF3188, and andrographolide bring about the anti cancer activity by a similar mechanism.
Highlights
We determined the effect of andrographolide and one of its novel semi-synthetic analog, DRF 3188, on the cell cycle of MCF 7 breast cancer cells
In this paper we show that andrographolide and DRF 3188 block the cell cycle at the G0-G1 phase, both in vitro and in vivo
On treatment with 10 μM Lovastatin for 24 h there was a 25% increase in the number of MCF 7 cells in the G0-G1 phase (Figure 2A) while there was a 52% and 42.3% decrease in the number of cells entering the G2-M and synthetic phase' (S phase) of the cell cycle, respectively. This indicated that the Lovastatin treated cells were arrested in the G0-G1 phase of the cell cycle
Summary
We determined the effect of andrographolide and one of its novel semi-synthetic analog, DRF 3188, on the cell cycle of MCF 7 breast cancer cells. 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. 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. Intense research efforts are on for identifying cell cycle specific inhibitors for the treatment of cancer (Ex: Flavopiridol)
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