CA 432 was 10 fold more effective than CA 4 in the HT 29 cells indicating a possible practical advantageous asset of the ethylene bridge azetidinone alternative. The fibrosarcoma cell line GDC-0068 and a adenocarcinoma cell line CT 26 were selected for further studies to understand the molecular mechanism of combretastatin induced cell death in colon carcinomas. In agreement with recent publications, we established that tubulin is the molecular target of both CA 4 and its artificial by-product, cells were derived by CA 432 in both HT 1080 and CT 26 colon cancer. The result of CA 4 and CA 432 on the cell cycle over time was next established by flow cytometric analysis of the DNA content of propidium iodide stained cells. As shown in Fig. 2, a significant G2M arrest was induced by both compounds at 8 h. In HT 1080 cells a from G2M cell cycle arrest resulted in an occasion dependent increase in cell death as based on an increase in the proportion of cells in sub G1. In comparison, in CT 26 cells a release from G2M yielded two different outcomes, polyploidy and cell death. CA 4 and CA 432 induced equally cell death and polyploidy in Caco 2 cells subsequent to mitotic launch. Both compounds induced cell death although not polyploidy in HT 29 cells at cytotoxic concentrations. In summary, prolonged experience of combretastatins could fundamentally cause cell death or continuing DNA replication without cell division in colon cancer cells. Apoptosis, Autophagy and oncotic/necrotic Lymph node will be the principle pathways of programmed cell death, although others have been found. Apoptosis is characterized by different morphological changes including cell shrinkage and chromatin condensation and apopto tic guns including DNA fragmentation and caspase activation. The traditional options that come with Type I cell death were observed in HT 1080 cells subjected to CA 4 and CA 432. As an example, the morphological features of apoptosis including cell shrinkage, chromatin condensation and the apoptotic Flupirtine bodies were visible in cytospin preparations of CA 4 and CA 432 addressed HT 1080 cells but were absent in get a grip on cells. Furthermore, the activation of caspases by the combretastatins in HT 1080 cells was confirmed by a fluorescent based quantitative assay, the disappearance of cleavage of the caspase 3 substrate and total length caspase 3, poly polymerase by western blotting. More over, pre therapy of HT 1080 cells with the typical caspase inhibitor Z VAD FMK dramatically inhibited combretastatin induced cell death. Collectively, these findings suggest combretastatins produce a dependent Type I cell death in the fibrosarcoma HT 1080 cells. In contrast, CT 26 adenocarcinoma cells subjected to combretastatins elevated in cell size and contained numerous nuclei and vacuoles and the cell death seen was caspase independent.