Disease relevance of AI3-62089

• A similar dose-response relationship for papilloma and carcinoma formation was observed when chrysarobin was applied once weekly [1].
• Chrysarobin and TPA were compared at optimal promoting doses for their ability to induce: (a) skin edema, (b) epidermal hyperplasia, and (c) epidermal ornithine decarboxylase [2].
• The progression of papillomas to carcinomas was examined in all chrysarobin-treated groups and compared with three groups of mice treated with 3.4 nmol TPA [1].
• Chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone) was an effective skin tumor promoter when applied twice weekly with dose-dependent increases in both papillomas and squamous cell carcinomas between 25 and 100 nmol/mouse [1].
• Skin sections from mice treated with chrysarobin displayed overt signs of epidermal toxicity including altered basal cell morphology and a decreased number of basal cells per 125 micron of basement membrane [3].

High impact information on AI3-62089

• Stat1, Stat3, and Stat5 were activated in mouse epidermis after treatment with different classes of tumor promoters, including 12-O-tetradecanoylphorbol-13-acetate (TPA), okadaic acid, and chrysarobin [4].
• At optimal promoting doses, chrysarobin treatment produced a maximum number of papillomas that was approximately 1/3 that produced by TPA (6.4 versus 17.0 papillomas per mouse, respectively) [5].
• In addition, chrysarobin treatment following 10 wk of TPA promotion did not enhance the progression of preexisting papillomas to carcinomas [5].
• Following treatment with both chrysarobin and TPA, higher levels of epidermal DNA synthesis correlated closely with higher molar ratios of spermidine/spermine, indicating a strong relationship between epidermal spermidine levels and epidermal cell proliferation induced by both promoters [6].
• Antipsoriatic anthrones with modulated redox properties. 2. Novel derivatives of chrysarobin and isochrysarobin--antiproliferative activity and 5-lipoxygenase inhibition [7].

Anatomical context of AI3-62089

• Chrysarobin induced a significant infiltration of PMNs into the dermis of DBA/2 mice whereas in C57BL/6 mice there was only a slight dermal infiltration of PMNs [8].
• Although not significantly different, maximum elevations in epidermal thickness, total number of nucleated epidermal cells, and dark basal keratinocytes (DCs) induced by 220 nmol chrysarobin occurred at 96 h after treatment, while those induced by 3.4 nmol TPA occurred at 48 h [3].
• A single application of TPA but not chrysarobin resulted in a rapid translocation of protein kinase C (PKC) to the membrane; however, treatment with both promoters ultimately led to a time-dependent loss of PKC activity in both membrane and cytosol fractions [9].

Associations of AI3-62089 with other chemical compounds

• Retinoic acid (RA) inhibited skin tumor promotion by chrysarobin; however, the degree of inhibition was dependent on the treatment protocol [10].
• A 0.5 or 0.25% supplement of alpha-difluoromethylornithine (alpha-DFMO) in the drinking water inhibited the induction of epidermal ODC following chrysarobin (220 nmol/mouse) treatment by 85 or 70%, respectively [10].
• Ascorbyl palmitate (AP), given 5 min prior to the promoter at 1 and 4 mumol doses, effectively inhibited the induction of ODC activity (28% and 59%, respectively) by 220 nmol of chrysarobin [11].
• The present study was designed to compare the skin tumor promoting and epidermal ornithine decarboxylase (ODC) inducing activities of various structural analogs of anthralin (1,8-dihydroxy-9-anthrone) and chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone) [12].
• Other non-TPA type tumor promoters, i.e., chrysarobin, 7-bromomethylbenz[a]anthracene, benzoylperoxide, okadaic acid and palytoxin, did not potentiate the TPA-caused PGE2 release [13].

Gene context of AI3-62089

• A single topical treatment of either 12-O-tetradecanoylphorbol-13-acetate (TPA) or chrysarobin or a single full-thickness wound induced the expression of HB-EGF and AR in mRNA samples isolated from whole mouse skin [14].
• Subsequently, 125I-EGF binding increased to approximately 200% of control in epidermal membrane preparations from both TPA- and chrysarobin-treated mice [9].
• A single topical application of TPA or chrysarobin induced elevated levels of transforming growth factor-alpha (TGF-alpha) mRNA at 6 h or 15-24 h, respectively [9].
• The peaks of Cx26 and Cx43 expression and Cx31.1 inhibition appeared 12 h after TPA application and 24 h after OA and chrysarobin application [15].
• Total RNA was isolated from SENCAR mouse epidermis at various times after single topical treatments with TPA (3.4 nmol), chrysarobin (220 nmol), okadaic acid (2.5 nmol), and thapsigargin (8.5 nmol) [16].

Analytical, diagnostic and therapeutic context of AI3-62089

• TPA treatment produced several waves of DNA synthesis at approximately 18 and 48 h after treatment, while chrysarobin produced a single broad peak at 72 h after treatment [6].

References