Disease relevance of Perilla alcohol

• Activation of the transforming growth factor beta signaling pathway and induction of cytostasis and apoptosis in mammary carcinomas treated with the anticancer agent perillyl alcohol [1].
• The effects of perillyl alcohol were not limited to these B-lymphoma cells but were also observed in MDA-MB 468 cells, an estrogen receptor-negative breast cancer cell line [2].
• Prior to the efficacy study, the MTD of perillyl alcohol was determined in male F344 rats in a 6-week subchronic toxicity study and found to be a 2.5-g/kg diet when added to the AIN-76A diet [3].
• Perillyl alcohol at the 1-g/kg level significantly inhibited the incidence (percentage of animals with tumors) and multiplicity (tumors/ animals) of invasive adenocarcinomas of the colon, whereas perillyl alcohol at 2 g/kg diet inhibited the incidence of total adenocarcinomas of the colon and small intestine as compared to the control diet [3].
• Inhibitory effects of perillyl alcohol on UVB-induced murine skin cancer and AP-1 transactivation [4].

High impact information on Perilla alcohol

• This apoptosis was directly due to NF-kappaB because its prior activation abolished the cell killing effects of perillyl alcohol treatment [2].
• Whereas sequence-specific DNA-binding factors dictate the expression patterns of genes through transcriptional regulation, those transcriptional factors influencing constitutive cell survival with perillyl alcohol treatment are not well studied [2].
• The cell death induced by the monoterpene anticancer agent perillyl alcohol correlates to the increased expression of certain proapoptotic genes known to influence cell survival [2].
• Perillyl alcohol (POH) is a monoterpene found in lavender, spearmint, and cherries [5].
• These agents induced either apoptosis in the basal epithelium (difluoromethylornithine) or both apoptosis and vacuolation of basal epithelial cells (perillyl alcohol) [6].

Chemical compound and disease context of Perilla alcohol

• The three genes were successfully coexpressed in Pseudomonas putida by using the broad-host-range vector pCom8, and the recombinant converted limonene to perillyl alcohol with a specific activity of 3 U/g (dry weight) of cells [7].
• In this study, we investigated the effects of limonene and limonene-related monoterpenes, perillyl alcohol and perillic acid, on cell growth, cell cycle progression, and expression of cyclin D1 cell cycle-regulatory gene in T-47D, MCF-7, and MDA-MB-231 breast cancer cell lines [8].
• Monoterpenes such as perillyl alcohol have been shown to cause the complete regression of advanced mammary carcinomas [9].
• This study examines the effect of perillyl alcohol, an oral hydroxylated D-limonene, on the development of intimal hyperplasia and its associated smooth muscle cell physiological responses in an experimental model of vein bypass grafting [10].
• We then tested the hypotheses that perillyl alcohol and farnesol would have chemopreventive activity toward pancreatic cancer and would increase Bak expression and apoptosis in vivo [11].

Biological context of Perilla alcohol

• Our studies also indicate that the colon tumors of animals fed perillyl alcohol exhibited increased apoptosis as compared to those fed the control diet [3].
• PURPOSE: Perillyl alcohol (POH) displays preventive and therapeutic activity against a wide variety of tumor models, and it has been suggested that this might be associated with the ability of POH to interfere with Ras prenylation [12].
• We conducted a phase I dose-escalation trial of perillyl alcohol (POH; NSC 641066) given p.o. on a continuous four times a day basis to characterize the maximum tolerated dose, toxicities, pharmacokinetic profile, and antitumor activity [13].
• In this study, the monoterpene perillyl alcohol (POH) was found to induce transient expression of the c-jun and c-fos genes transcriptionally [14].
• Although R- and S-limonene are only weak inhibitors of the isoprenylation enzymes, their major metabolites, perillic acid and perillyl alcohol, are more potent inhibitors, with IC50 values in the low mM range [15].

Anatomical context of Perilla alcohol

• In fibroblasts, insulin increased the enzymatic activity of GGTase II 2.5-fold after 1 h of incubation, an effect that is blocked by perillyl alcohol, an inhibitor of prenyltransferases, but not by the geranylgeranyltransferase I inhibitor, GGTI-298, or the farnesyltransferase inhibitor, alpha-hydroxyfarnesylphosphonic acid [16].
• Perillyl alcohol has antitumor activity toward pancreas and other cancers with low toxicity [17].
• Perillyl alcohol selectively induces G0/G1 arrest and apoptosis in Bcr/Abl-transformed myeloid cell lines [18].
• (+)- and (-)-limonene enantiomers were found to be oxidized to their respective trans-carveol (6-hydroxylation) and perillyl alcohol (7-hydroxylation) derivatives in greater amounts by liver microsomes of male rats than those of female rats [19].
• Cytotoxicity and biotransformation of the anticancer drug perillyl alcohol in PC12 cells and in the rat [20].

Associations of Perilla alcohol with other chemical compounds

• Both limonene and perillyl alcohol are currently being evaluated in phase I clinical trials in advanced cancer patients [21].
• PURPOSE: Perillyl alcohol (POH) (4-isopropenyl-cyclohexenecarbinol) is a member of the monoterpenes, which are present in various fruits and vegetables [22].
• As a consequence, nuclear lamins and ras oncoproteins remain in nascent states, and cells do not proliferate. gamma-Tocotrienol, perillyl alcohol, geraniol and d-limonene suppress hepatic HMG-CoA reductase activity, a rate-limiting step in cholesterol synthesis, and modestly lower serum-cholesterol levels of animals [23].
• Also, agents such as perillyl alcohol and lovastatin that interfere with protein isoprenylation and, hence, inhibit oncogene activation may protect against aberrant K-ras expression [24].
• Agents at various stages of study include the green tea catechin epigallocatechin gallate (EGCG), the limonene derivative perillyl alcohol, the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO), selenium, retinoids and salicylates [25].

Gene context of Perilla alcohol

• Of 11 recombinant human P450 enzymes (expressed in Trichoplusia ni cells) tested, CYP2C8, 2C9, 2C18, 2C19, and CYP3A4 catalyzed oxidations of (+)- and (-)-limonenes to respective carveols and perillyl alcohol [26].
• Perillyl alcohol inhibits the expression and function of the androgen receptor in human prostate cancer cells [27].
• Perillyl alcohol induces c-Myc-dependent apoptosis in Bcr/Abl-transformed leukemia cells [28].
• In vivo treatment of ANA-positive B6.Sle1ab mice with the ras pathway inhibitor, perillyl alcohol, suppressed the increase of ANA [29].
• We recently reported that the monocyclic monoterpene, perillyl alcohol (POH) selectively induces in Bcr/Abl transformed cells, G0/G1 arrest and apoptosis [30].

Analytical, diagnostic and therapeutic context of Perilla alcohol

• Chemoprevention of colon carcinogenesis by dietary perillyl alcohol [3].
• The mechanisms of action of the anticancer agent perillyl alcohol (POH), presently in Phase II clinical trials, were investigated in advanced rat mammary carcinomas [1].
• The monoterpene perillyl alcohol (POH) has preventive and therapeutic effects in a wide variety of pre-clinical tumor models, including those for breast cancers, and is currently being tested in human phase I clinical trials [31].
• METHODS: The present paper demonstrates the effectiveness of the monoterpene perillyl alcohol (POH) as potent radiosensitizer on DU145 and PC3 cell lines by performing clonogenic survival assays, cycle analysis, and assays to detect viability, apoptosis, and Fas receptor/ligand by flow cytometry [32].
• The construct was subsequently used in a 2-liter bioreactor to produce perillyl alcohol on a scale of several grams [7].

References