Tumor-promotion agents

Under basal conditions, PKC is predominantly a cytoplasmic protein. Upon activation by Ca2+ or DAG, the enzyme associates with the plasma membrane, the site of many of its known physiological substrates, including receptors and ion channels. In fact, the translocation of PKC from the cytoplasm to the membrane has long been used as an experimental measure of enzyme activation. Such translocation has often been assayed by phorbol ester binding phorbol esters are tumor-promoting agents that selectively bind to and activate PKC. The molecular basis of the translocation of PKC from the cytoplasm to the plasma membrane has been solved. Subsequent to activation, PKC binds with high affinity to a series of membrane-associated proteins, termed receptors for... 

Van Duuren BL, Goldschmidt BM. 1976. Cocarcinogenic and tumor promoting agents in tobacco carcinogenesis. J Natl Cancer Inst 56 1237-1242. 

Yoshida, and S. Mizusaki. Identification of cembratriene-4,6-diol as anti-tumor-promoting agent from cigarette smoke condensate. Carcinogenesis... 

The cytosolic concentration of free Ca2+ is generally at or below 100 mi, far lower than that in the surrounding medium, whether pond water or blood plasma. The ubiquitous occurrence of inorganic phosphates (Pj and I l ,) at millimolar concentrations in the cytosol necessitates a low cytosolic Ca2+ concentration, because inorganic phosphate combines with calcium to form relatively insoluble calcium phosphates. Calcium ions are pumped out of the cytosol by a P-type ATPase, the plasma membrane Ca2+ pump. Another P-type Ca2+ pump in the endoplasmic reticulum moves Ca2+ into the ER lumen, a compartment separate from the cytosol. In myocytes, Ca2+ is normally sequestered in a specialized form of endoplasmic reticulum called the sarcoplasmic reticulum. The sarcoplasmic and endoplasmic reticulum calcium (SERCA) pumps are closely related in structure and mechanism, and both are inhibited by the tumor-promoting agent thapsigargin, which does not affect the plasma membrane Ca2+ pump. 

No studies were located regarding cancer in animals after dermal exposure to barium. However, results of one skin-painting study with mice suggest that barium hydroxide extract derived from tobacco leaf may act as a tumor-promoting agent (Van Duuren et al. 1968). In this study, mice were treated dermally for an unspecified period of time with either barium hydroxide extract alone, 7,12-... 

Thastrup O, Foder B, and Scharff O. (1987). The calcium mobilizing tumor promoting agent, thapsigargin, elevates the platelet cytoplasmic free calcium concentration to a higher steady state level. A possible mechanism of action for the tumor promotion. Biochem Biophys. Res. Commun. 142,654-660. 

The primary toxic effect elicited by chrysene is oncogenicity. Several studies have been conducted in mice in which chrysene (diluted in a variety of agents) was applied dermally either as a single dose (followed by a tumor promoting agent) or as multiple doses. Increased incidences of dermal tumors (papillomas and carcinomas) were observed in mice administered chrysene and a tumor promoting agent. Several studies were also conducted in which mice or rats received intramuscular or subcutaneous injections of chrysene... 

Phorbol Ester A potent tumor-promoting agent in mouse skin and has numerous biochemical effects such as activating PKC isoenzymes and stimulating expression of iNOS and COX-2... 

Ao L, Liu JY, Liu WB, Gao LH, Hu R et al (2010) Comparison of gene expression profiles in BALB/c 3T3 transformed foci exposed to tumor promoting agents. Toxicol In Vitro 24 430-138... 

Krutovskikh VA, Mesnil M, Mazzoleni G, et al. 1995. Inhibition of rat liver gap junction intercellular communication by tumor-promoting agents in vivo Association with aberrant localization of connexin proteins. Lab Invest 72 571-577. 

Tetradecanoylphorbol 13-acetate (TPA) and other diterpene esters from the plant family Euphorbiaceae are well-known as tumor-promotion agents [85]. Thus, inhibition of the biological effects induced by TPA has been considered as a promising strategy [68]. To date, two short-term cell-based in vitro bioassays using TPA as a tumor-promoter have been developed to evaluate the potential cancer chemopreventive activities of several lignans isolated from Hernandia species, namely, inhibition of Epstein-Barr virus early antigen activation [6] and the inhibition of the transformation of JB6 mouse epidermal cells [7]. 

Phenol, which is a weak tumor-promoting agent, is indeed an inhibitor of tumorigenesis when applied simultaneously with benzo[a]pyrene. 

Bock, EG., R.J. Shamberger, and H.K. Myers Tumor-promoting agents in unbumed cigarette tobacco Nature 208(1965)584-585. 

Van Duuren, B.L. and B.M. Goldschmitt Carcinogenic and tumor-promoting agents in tobacco carcinogenesis J. Natl. Cancer Inst. 56 (1976) 1237-1242. 

Lankas GR, Baxter CS, Christian RT. 1978. Effect of alkane tumor-promoting agents on chemically induced mutagenesis in cultured V79 Chinese hamster cells. J Toxicol Environ Health 4 37-41. 

Boutwell, R.K., 1967, Phenolic compounds as tumor-promoting agents, in "Phenolic Compounds and Metabolic Regulation", B.J. 

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