Disease relevance of E 5166

• After a median follow-up of 38 months, 12 patients in the polyprenoic acid group (27 percent) had recurrent or new hepatomas as compared with 22 patients in the placebo group (49 percent, P = 0.04) [1].
• When given orally at a dose of 200 mg/kg body weight, beta-carotene regressed the skin papilloma to some extent (-16% at 14 days), although its effect was much weaker than that of E-5166 (-43%) [2].
• E-5166 also significantly reduced tumor incidences of experimental hepatomas induced by chemical carcinogen in rats as well as in "spontaneous" hepatoma-bearing mice (C3H/HeNCrj) genetically determined [2].
• Morphological differentiation of human neuroblastoma cell lines by a new synthetic polyprenoic acid (E5166) [3].
• These results indicate that because it inhibits ODC activity E-5166 can be utilized for the treatment of hyperproliferative skin diseases [4].

High impact information on E 5166

• Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group [1].
• Polyprenoic acid in hepatocellular carcinoma [5].
• We developed an acyclic retinoid, polyprenoic acid, that inhibits hepatocarcinogenesis in the laboratory and induces differentiation and apoptosis in cell lines derived from human hepatoma [1].
• Furthermore, E-5166 inhibited the EGF-stimulated phosphatidylinositol (PI) turnover of pig epidermis [6].
• A new synthetic vitamin A-like compound (polyprenoic acid derivative, E-5166) has a strong in vitro binding affinity to intracellular binding proteins for acidic retinoids [6].

Biological context of E 5166

• Inhibitory effects of polyprenoic acid (E5166) on production and secretion of alpha-fetoprotein and on cell kinetics in human hepatoma cells [7].
• The inhibitory effect appeared to be reversible, since removal of E-5166 from the culture medium resulted in a subsequent return of cell proliferation [8].
• These results indicate that both polyprenoic acid and retinol can facilitate wound healing [9].

Anatomical context of E 5166

• Using C3H/10T-1/2 mouse fibroblasts, we tested whether polyprenoic acid (E-5166) inhibits radiogenic and chemically induced transformation in vitro [10].
• This study examined the effects of E-5166 on the proliferation of keratinocytes [8].
• Effects of in vivo exposure to the synthetic polyprenoic acid, 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166) using 6 groups of rats treated simultaneously or individually with phenobarbital (PB) or with p,p'-dichlorodiphenyltrichloroethane (DDT) on the gap junctions of hepatocytes were examined by freeze-fracture analysis [11].
• Both enhanced the induction of platelets in the peripheral blood but neutrophils were not affected by polyprenoic acid [9].
• Among 10 synthetic polyprenoic acid derivatives, 3,7,11,15-tetramethyl-2,4,6,10,14 hexadecapentaenoic acid (compound 1) was found to have the strongest binding affinity to cellular retinoic acid-binding protein (CRABP) from rat testis [12].

Associations of E 5166 with other chemical compounds

• In order to elucidate the anti-inflammatory activity of E-5166, we studied the effect of E-5166 on the epidermal growth factor (EGF)-stimulated arachidonic acid (AA) release of pig epidermis [6].
• Furthermore, E-5166 showed significantly stronger antiproliferative capacity than Ro 10-9359, one of the aromatic retinoids, on Pam 212 cells and normal human keratinocytes [8].
• Other novel chemopreventative agents, such as glycyrrhizin and polyprenoic acid, may also have a role in preventing HCC, but they require further study before they can be recommended for widespread use [13].
• Inhibitory effects of chlorogenic acid, reserpine, polyprenoic acid (E-5166), or coffee on hepatocarcinogenesis in rats and hamsters [14].

Gene context of E 5166

• Experiment 3: The number of hepatocellular foci in male ACI/N rats given 0.02% FAA diet for 13 wk and E-5166 by gavage (40 mg/kg body weight, 3 times/wk) for 16 wk after the end of FAA exposure was significantly smaller than that in rats given FAA diet alone [14].
• Previous clinical trials have shown the effectiveness of the following: polyprenoic acid (acyclic retinoid) for hepatocellular carcinoma; tamoxifen for breast cancer; retinoic acids for head and neck tumor; and aspirin, a COX-2 inhibitor, for colorectal cancer [15].

Analytical, diagnostic and therapeutic context of E 5166

• Post resection adjuvant therapies have included interferon, polyprenoic acid, and adoptive immunotherapy [16].
• These results suggest that the polyprenoic acid is a good candidate for clinical chemoprevention of hepatoma, targetting its precancerous stage when intracellular receptors for acidic retinoid have emerged [17].

References