Oncogene inhibition

Inhibits proliferation of tumors, cell lines or fibroblasis transformed by H-ras or trk oncogenes. Inhibits thymidylate synthetase and depletes dTTP it forms nucleotides that can be incorporated into RNA and DNA and induces p53-dependent apoptosis. 

Bennett MR, Littlewood TD, Hancock DC, Evan GI, Newby AC (1994) Down-regulation of the c-myc proto-oncogene inhibition of vascular smooth muscle cell proliferation a signal for growth arrest Biochem J 302 701-708... 

EGE) receptor Hdm2 oncogene Inhibits tumor growth MCE-7 xenografts 141... 

The streptovaricins inhibit the reverse transcriptase of some RNA oncogenic vimses that may be involved in the process of viral transformation (see Antiviral agents). The atropisostreptovaricins again have similar activities to the corresponding natural isomers. The streptovals and streptovarone exhibit gready improved activity against reverse transcriptase relative to the streptovaricins (85), but their in vitro activities were low (86). The damavaricins also inhibit reverse transcriptase (4) as well as tumor cell growth (87). 

Kim Y, Yoon JW, Xiao X et al (2007) Selective down-regulation of glioma-associated oncogene 2 inhibits the proliferation of hepatocellular carcinoma cells. Cancer Res 67(8) 35 83-3593... 

Shammas M.A., Simmons C.G., Corey D.R., Reis R.J.S. Telomerase inhibition by peptide nucleic acids reverses immortality of transformed human cells. Oncogene 1999 18 6191-6200... 

Many vimses, both DNA and RNA containing, will cause cancer in animals. This so-called oncogenic achvity of a vims can be demonstrated by the observahon of tumour formahon in inoculated experimental animals and by the ability of the vims to transform normal tissue culture cells into cells with malignant characteristics. These transformed cells are easily recognizable as they exhibit such properties as rapid growth and frequent mitosis, or loss of normal cell contact inhibition, so that they pile up on top of each other instead of remaining in a well-organized layer. 

HU G, HAN c and chen j (1995) Inhibition of oncogene expression by green tea and (-)-epigallocatechin gallate in mice Nutrition and Cancer 24, 203-9. 

Zhao, X., Singh, B and Arlinghaus, R. B. (1991). Inhibition of c-mos protein kinase blocks mouse zygotes at the pronuclei stage. Oncogene 6 1423-1426. 

Nahum, A., K. Hirsch, M. Danilenko et al. 2001. Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27(Kipl) in the cyclin E-cdk2 complexes. Oncogene 20(26) 3428-3436. 

Neckers, L., Whitesel, L., Rosolen, A., and Geselowitz, D.A., Antisense inhibition of oncogene expression, Critical Reviews in Oncogenesis, 1992, 3, 175-231. 

Kim, H. A., Rosenbaum, T., Marchionni, M. A., Ratner, N. and DeClue, J. E. Schwann cells from neurofibromin deficient mice exhibit activation of p21ras, inhibition of cell proliferation and morphological changes. Oncogene 11 325-335,1995. 

Antidepressant treatment has, in recent studies, been shown to upregulate the cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) cascade and expression of BDNF [59]. This upregulation of CREB and BDNF raises the possibility that antidepressant treatment could oppose the cell death pathway, possibly via increased expression of the oncogene Bcl-2. Studies are necessary to determine if antidepressant treatment increases Bcl-2 expression. Increased expression of Bcl-2 in brain and cultured cells, and inhibition of apoptosis of cultured cerebellar granule neurons have been reported with lithium treatment [57]. Mice lacking the BDNF TrkB receptor fail to show behavioral and neurogenic responses to antidepressants. 

Ral has attracted much interest in recent years, not least because it was demonstrated to mediate part of Ras function as described above. In contrast to Rap, which rather inhibits Ras signaling, Ral is part of one of the essential Ras-activated pathways. Moreover, it has proved to be acting in parallel with the Raf pathway in cell transformation induced by oncogenic Ras [37, 77]. The case of Ral demonstrates the complexity - and the incomplete knowledge and understanding - of signal transduction. Ral can also be activated by Rap mediated by Rif [103] and, alternatively, by binding of a calcium/calmodulin complex to the Ral C-terminus which obviously does not affect the nucleotide state of Ral [111]. 

---