Inhibitors of cell division

One of the most important of the tumor suppressor genes is Rb. Mutant Rb genes are found in many human tumors, including retinoblastoma (as cited earlier). The Rb protein is a potent inhibitor of cell division. Loss of Rb function will lead to abnormal cell division and, ultimately, to cell transformation. 

Natural Products and Semi-Synthetics - Several naturally occurring compounds or their derivatives have received considerable attention this past year because of their clinical potential. The epipodophyllotoxins, VP-16,213 (7 ) and VM-26 (8), known to be potent inhibitors of cell division, were found not to be inhibitors of microtubule assembly as are... 

Catharanthus roseus, which is a potent inhibitor of cell division, and will be discussed in the next section) and prednisone (a steroid) were popular and highly effective examples. This combination induced complete remission in up to 95% of patients. One deficiency of this chemotherapeutic regimen was the failure of these drugs to penetrate the brain, and this would provide a reservoir of leukaemia cells that could reproduce, repopulate the body and kill the patient. The American physician Donald Pinkel, of St. Jude s Children s Hospital in Memphis Tennessee, neatly solved this problem by irradiating the skulls of his patients with X-rays (i.e., radiotherapy) in order to kill this hidden population of cells. 

In addition to abnormal cellular metabolism one of the characteristics of cancer cells is an increased rate of mitosis, and as a result an increased sensitivity to inhibitors of cell division. Thpreforc, the fact that DNA is the cell component most sensitive to alkylating agents may explain to a certain extent the increased reactivity of cancerous tissues towards these substances. 

Inhibitor of cell division in tobacco tissue culture (297)... 

Abscisic Acid. ABA is a potent inhibitor of cell division in the developing roots of Lemna minor (Newton 1977). This effect, plus an apparent direct inhibitory effect on cell expansion in Lemna roots, contributes to the overall inhibitory action of ABA on root elongation in this aquatic plant. 

Anaviev and Gvozdev (1974 a) have studied the position effect of the mosaic type in D. melanogaster with the chromosomal mutation Dp (l f)R and the translocation of the euchromatic region 1A3-4-3A1-2 of the X chromosome to the centromere heterochromatin. According to their data, there is a delay of replication of the translocated euchromatin. RNA synthesis here was reduced to 60% of normal. These data show that the position effect is accompanied by alterations at the transcriptional level. The resistance of the eye mosaic peculiarities to inhibitors of cell division and RNA synthesis added at the end of the first larval stage does not contradict the above statements (Baker, 1967 Perez-Davila and Baker, 1967). 

Fusetani, N., Y. Kato, S. Matsunaga, and K. Hashimoto Bioactive Marine Metabolites. V. Two New Furanosesterterpenes, Inhibitors of Cell Division of the Fertilized Starfish Eggs, from the Marine Sponge Cacospongia scalaris. Tetrahedron Lett. 25, 4941 (1984). 

In rod-shaped bacteria such as Escherichia coh, the proper placement of the cell division site is maintained by the MinC, MinD, and MinE proteins encoded by the minB locus [2,3]. In this system, the MinC and MinD proteins act in concert forming an inhibitor of cell division capable of blocking septum formation at all potential division sites (polar and midcell sites). The MinE protein gives topological specificity to the MinCD division inhibitor by restricting its activity to polar division sites, thus ensuring that separation is limited to the proper division site at midcell [6]. MinD is an ATPase inE. coh [5]. 

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