Methyl tumor promoter

Ftirstenberger, G., Schurich. B., Kaina, B., Petrusevska, R.T., Fusenig, N.E. Marks, F. (1989) Tumor induction in initiated mouse skin by phorbol esters and methyl methanesulfonate correlation between chromosomal damage and conversion ( stage I of tumor promotion ) in vivo. Carcinogenesis, 10, 749-752... 

Methylation at C-4 of sterol nucleus was one of the other factors affecting activity enhancement. Thus, in general, 4-methylsterols (14,15) and 4,4-dimethylsterols (8,13) exhibited higher activity than 4-desmethylsterols. A similar structure-activity relationship was observed also in the HHPA-induced inflammation on mouse ear [35]. Whereas cholesterol (7) did not show inhibitory activity, several 4,4-dimethylcholestane derivatives, 0-12, exhibited activity. 4,4-Dimethylcholestane-3a,5a-diol (12) was the most potent inhibitor its activity was comparable to that of ursolic acid (210) [35]. Compound 12 reduced also the inflammation induced by teleocidin B (3), one of the indole alkaloid-type of tumor promoters [53]. 

Moser GJ, Wong BA, Wolf DC, Fransson-Steen RL, Goldsworthy TL (1996) Methyl tertiary butyl ether lacks tumor-promoting activity in M-nitrosodiethylamine-initiated BeCsFi female mouse liver. Carcinogenesis 17 2753-2761... 

The lignans enterodiol, enterolactone and NDGA and the lignan metabolite methyl p-hydroxyphenyllactate interfere with mitogenic and tumor promotional signal transduction pathways [153], NDGA and methyl p-hydroxyphenyllactate did not inhibit 12-G-tetradecanoylphorbol-13-acetate (TPA) mediated c-fos transcription, and enterolactone and enterodiol had only a weak inhibitory effect. NDGA at 0.1-10 p.mol/L increased c-fos mRNA levels. 

Reddy and coworkers (88-90) evaluated carcinogenic or tumor-promoting activity of cholesterol, a-epoxide, triol and primary and secondary bile acids, with and without induction by N-methyl-N -nitro-N-nitrosoguanidine (MNNG). Tumor development required MNNG, and bile acids acted as promoters. Cholesterol and its metabolites were not found to have promoting activity. Other Cancers... 

The tnmor promotion activity of OA and DTX-1 was first observed in vivo on monse skin, initiated with 7,12-dimethylbenz[a]anthracene (DMBA), and snbsequently in rat glandular stomach, initiated with /V-methyl-M-nitro-/V-nitrosognanidine (MNNG)." " The in vivo tumor-promoting activity of OA and DTX-1 was confirmed also in in vitro cell cnltnres. In particular, exposure of mouse embryonic fibroblasts BALB/3T3 to the initiator 3-methylcholanthrene for 72 h, followed by treatments for 2 weeks with OA (12.4 nM or 24.8 nM) or DTX-1 (3.66 nM) led to transformation of cells. However, OA tetramethyl ether (34.7 nM) did not affect initiated cells transformation. Moreover, OA failed to indnce transformation of cells without 3-methylcholanthrene pretreatment and did not show initiating activity when cells were treated first with the toxin and then with the tumor promoter... 

The tumor-promoting activity of OA can be also partially related to other actions at cellular level, such as oxidation of different substrates, methylation of DNA bases, and inhibitory mechanisms of gap intracellular communication, which is believed to be of importance in the promotion stage of carcinogenesis. An additional factor hypothesized to contribute to the tumor promotion by OA is amplification of genes conferring multidrug resistance to cells. ... 

Arffmann, E. and Glavind, J., 1971, Tumor-promoting activity of fatty acid methyl esters in mice, Experientia, 27 1465-1466. Bababunmi, E.A, 1978, Toxins and carcinogens in the environment An observation in the tropics, J. Toxicol. Environ. Health, 4 691-699. 

Myricetin has been reported to have a role in anticarcinogenesis. Polycyclic aromatic hydrocarbons, such as benzo(a)pyrene, cause skin and lung cancer in experimental animals. Myricetin reduces polycyclic aromatic hydrocarbon-induced tumors in the skin. Topical administration of myricetin provided significant protection against skin tumorige-nicity in SENCAR mice that were given 7,12-dimethylbenz(a)anthra-cene, benzo(a)pyrene and N-methyl-N-nitrosourea as tumor initiators, followed by 12-0-tetradecanoylphorbol-13-acetate as a tumor promoter. Additionally, myricetin delayed onset and subsequent recurrence of skin tumors in BALB/c mice that were administered benzo(a)p5uene, 7,12-dimethylbenz(a)anthracene, and N-methyl-N-nitrosourea as tumor initiators and 3-methyl-cholanthrene as a tumor promoter [19]. 

Digiovanni J, Boutwell R K 1983 Tumor promoting activity of l,8-dihydroxy-3-methyl-9-anthrone (chrysarobin) in female Senear mice. Carcinogenesis 4 281-284... 

Rothem, L., Stark, M., Kaufman, Y., Mayo, L., and Assaraf, Y.G. (2004) Reduced folate carrier gene silencing in multiple antifolate-resistant tumor cell lines is due to a simultaneous loss of function of multiple transcription factors but not promoter methylation. Journal of Biological Chemistry. 279, 374-384. 

Fig. 2. Distribution of methylated CpGs in genomic DNA and their effect on transcription. 70-80% of all CpG dinucleotides are methylated in vertebrate genomes. mCpGs (filled lollipops) are randomly distributed throughout the genome but are excluded from regions with unusually high CpG density—CpG islands [16,17]. Most of the CpG islands are associated with gene promoters and maintained unmethylated (white lollipops) in all types of somatic cells. Aberrant methylation of CpG islands occurs in cancer cells and leads to silencing of tumor-suppressor and other essential genes [19-21].

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