Induction of differentiation in neuro-2A cells by the monoterpene perillyl alcohol

Shi, Wujie; Gould, Michael N.

doi:10.1016/0304-3835(95)03859-u

Cited by 36 publications

(22 citation statements)

References 14 publications

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“…Estudos em animais têm mostrado que o álcool períli-co é um agente quimioterápico eficaz na regressão de tumores de mama 20 , pâncreas 6,47 , fígado 37 , próstata 9 e agente quimiopreventivo nos tumores de cólon 43 , melanomas 35 e neuroblastomas 46 . Descreve-se que o álcool perílico atua na inibição da transdução de sinal através da membrana por inibir a farnesilação da proteína Ras 1,6,37 .…”

Section: Discussionunclassified

“…Álcool perílico e sua atuação em âmbito molecular O álcool perílico (figura 3), também chamado p-meta-1,7-dieno-6-ol ou 4-isopropenilciclo-hexenocarbinol, é um monoterpeno natural monocíclico hidroxilado, isolado dos óleos essenciais de lavanda, saliva, hortelã, menta, cerejas, sementes de aipo e várias outras plantas 1 . Estudos em animais têm mostrado que o álcool perílico é um agente quimioterápico eficaz na regressão de tumores de mama 20 , pâncreas 6,47 , fígado 37 , próstata 9 e agente quimiopreventivo nos tumores de cólon 43 , melanomas 35 e neuroblastomas 46 .…”

Section: Oncogenesunclassified

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2007

Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery

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Section: Discussionunclassified

Section: Oncogenesunclassified

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2007

Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery

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“…6,9,12,29 Tumors treated with monoterpenes have shown evidence of histological differentiation both in vitro and in vivo. 7,9,13 The mechanism for this anticancer activity has not yet been established. Monoterpenes inhibit mevalonate metabolism and can selectively prevent the prenylation of small GTP binding proteins, including ras.…”

Section: Discussionmentioning

confidence: 99%

“…5 In established rat mammary carcinomas, limonene produces complete regression in > 80% of the tumors. 6,7 Perillyl alcohol is five-fold more potent than limonene in producing regression in both early 8 and advanced mammary tumors, 9 and also has activity in vivo against cancers of the pancreas, 10 melanoma 11 and liver 12 and in vitro against neuroblastoma 13 and colon carcinoma. 14 The exact mechanism for the anticancer activity of monoterpenes has not been fully established.…”

Section: Introductionmentioning

confidence: 99%

“…7,9,12,17 Additional effects that may contribute to activity against established tumors include selective inhibition of prenylation of small GTP-binding proteins, 14,18,19 modulation of other signal transduction pathways, 12,20 or cell cycle blockade. 13,21 Monoterpenes also alter mevalonate metabolism and some of these effects may contribute to the antitumor activity. 22 Limonene reduces cholesterol biosynthesis through inhibition of 3-hydoxyl-3-methylglutaryl (HMG) coA reductase, 23 whereas perillyl alcohol affects a target further downstream.…”

Section: Introductionmentioning

confidence: 99%

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Phase I Study of Perillyl Alcohol in Patients with Refractory Malignancies

Murren¹,

Pizzorno²,

DiStasio³

et al. 2002

Cancer Biology & Therapy

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We treated 21 patients in a dose-finding and pharmacokinetic study of the monoterpene perillyl alcohol with the drug given orally in 3 divided doses on a chronic basis. The average number of days that patients remained on study was 48 (range 11-172). Fatigue and low-grade nausea were dose limiting. Using this schedule, a starting dose of 1.6 g/m2 with escalation to 2.1 g/m2 as tolerated is recommended. Two major metabolites were detectable and the mean peak plasma concentrations were 383 µM for perillic acid and 27 µM for dihydroperillic acid. The peak plasma concentration and the metabolite half-life were 2h and 1h post ingestion for perillic acid, and 4 h and 2.4 h for dihydroperillic acid, respectively. Stabilization of disease was observed in one of the 16 patients evaluable for response. Many of the gastrointestinal side effects that were poorly tolerated on a chronic basis may be partly related to the soybean oil base used in the current formulation. Further development of perillyl alcohol on this schedule would be facilitated by reformulation of the capsule.

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New agents for cancer chemoprevention

et al. 1996

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Clinical chemoprevention trials of more than 30 agents and agent combinations are now in progress or being planned.The most advanced agents are well known and are in large Phase III chemoprevention intervention trials or epidemiological studies. These drugs include several retinoids [e.g., retinol, retinyl palmitate, all-trum-retinoic acid, and 13-cis-retinoic acid], calcium, pcarotene, vitamin E, tamoxifen, and finaskride. Other newer agents are currently being evaluated in or being considered for Phase II and early Phase Ill chemoprevention trials. Prominent in this group are all-truns-N-(4-hydroxy phenylfretmamide (4-HPR) (alone and in combination with tamoxifen), 2-difluoromethylomithine (DFMO), nonsteroidal antiinflammatory drugs (aspirin, piroxicam, sulindac), oltipraz, and dehydroepiandrostenedione (DHEA). A third group is new agents showing chemopreventive activity in animal models, epidemiological studies, or in pilot clinical intervention studies. They are now in preclinical toxicology testing or Phase I safety and pharmacokinetics trials preparatory to chemoprevention efficacy trials. These agents include S-allyl-I-cysteine, curcumin. DHEA analog 8354 (fluasterone), genistein, ibuprofen, indole-3carbino1, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, sulindac sulfone, tea extracts, ursodiol, vitamin D analogs, and p-xylyl selenocyanate. A new generation of agents and agent combinations will soon enter clinical chemoprevention studies based primarily on promising chemopreventive activity in animal models and in mechanistic studies. Among these agents are more efficacious analogs of known chemopreventive drugs including novel carotenoids (e.g., acarotene and lutein). Also included are safer analogs which retain the chemopreventive efficacy of the parent drug such as vitamin D3 analogs. Other agents of high interest are aromatase inhibitors (eg.. (+)-vorozole), and protease inhibitors (e.g., Bowman-Birk soybean hypsin inhibitor). Combinations are also being considered, such as vitamin E with I-selenomethionine. Analysis of signal transduction pathways is beginning to yield classes of potentially active and selective chemopreventive drugs. Examples are rus isoprenylation and epidermal growth factor receptor inhibitors. 1997 Wiley-Liss, Inc.* Key words: cancer chemo reventive agents, drug development, retinoids, DFMO, NSAlDs, oltipraz, Phase I clinical trials, b hase II clinical trials evaluation in animal models and human clinical trials: A review.

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Induction of differentiation in neuro-2A cells by the monoterpene perillyl alcohol

Cited by 36 publications

References 14 publications

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Phase I Study of Perillyl Alcohol in Patients with Refractory Malignancies

New agents for cancer chemoprevention

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