curcumin and Papilloma

Topics: Administration, Oral; Administration, Topical; Allyl Compounds; Animals; Anticarcinogenic Agents; Antioxidants; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cocarcinogenesis; Curcumin; Female; Flavonoids; Humans; Male; Mice; Mice, Inbred SENCAR; Neoplasms, Radiation-Induced; Papilloma; Phenols; Phytotherapy; Plants, Medicinal; Polymers; Reactive Oxygen Species; Resveratrol; Silymarin; Skin Neoplasms; Stilbenes; Sulfides; Tea; Ultraviolet Rays; Zingiber officinale

Virgin coconut oil (VCO) and turmeric are traditionally being used in Indian cuisine systems; VCO is a natural combination of medium-chain triglyceride and polyphenols with established pharmacological potential. Curcumin isolated from turmeric is renowned for its anticancer properties, however, with limited clinical success due to poor bioavailability. Considering the lipophilic nature of VCO, curcumin added to VCO is expected to have synergistic/additive actions. In this study, the chemopreventive potential of curcumin enriched VCO (VCr) (4 and 8 mL/Kg orally) was analyzed in 7,12-dimethyl benz[a]anthracene (DMBA;470 nmoles/200 µL/week for two weeks topical)/croton oil (3% v/v in 200 µL acetone twice a week for 6 weeks topical) induced skin papilloma. In DMBA control animals, an average incidence of 13 papilloma/mice (latency period of 11.6 ± 1.5 weeks) was recorded. Pretreatment with VCrH (8 mL/kg) had a 60% inhibition of tumor index, and an increased latency period (12.5 ± 0.9 weeks). Additionally, DMBA/croton oil-induced reduction in glutathione levels and concomitant increase in thiobarbituric acid reactive substance (TBARS) in the skin microenvironment were restored by VCr. The study thus suggests that the VCr promotes antioxidant status

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthracenes; Coconut Oil; Curcumin; Mice; Papilloma; Plant Extracts; Skin Neoplasms; Tumor Microenvironment

This study aimed to evaluate the antimutagenic and anticarcinogenic activity of turmeric essential oil as well as to establish biochemical mechanisms of action. Antimutagenicity testing was accomplished using strains and known mutagens with and without microsomal activation. Anticarcinogenic activity was assessed by topical application of 7, 12 - dimethylbenz[a]anthracene (DMBA) as initiator and 1% croton oil as promoter for the induction of skin papillomas in mice. Inhibition of p450 enzymes by TEO was studied using various resorufins and aminopyrene as substrate. Turmeric essential oil (TEO) showed significant antimutagenic activity (p<0.001) against direct acting mutagens such as sodium azide (NaN3), 4-nitro-O-phenylenediamine (NPD) and N-methyl- N-nitro N'nitrosoguanine (MNNG). TEO was found to have significant antimutagenic effect (>90%) against mutagen needing metabolic activation such as 2-acetamidoflourene (2-AAF). The study also revealed that TEO significantly inhibited (p<0.001) the mutagenicity induced by tobacco extract to Salmonella TA 102 strain. DMBA and croton oil induced papilloma development in mice was found to be delayed and prevented significantly by TEO application. Moreover TEO significantly (P<0.001) inhibited isoforms of cytochrome p450 (CYP1A1, CYP1A2, CYP2B1/2, CYP2A, CYP2B and CYP3A) enzymes in vitro, which are involved in the activation of carcinogens. Results indicated that TEO is antimutagenic and anticarcinogenic and inhibition of enzymes (p450) involved in the activation of carcinogen is one of its mechanisms of action.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Antimutagenic Agents; Carcinogens; Cell Transformation, Neoplastic; Chemoprevention; Croton Oil; Curcuma; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Male; Mice; Mice, Inbred BALB C; Mutagenicity Tests; Mutagens; Oils, Volatile; Papilloma; Plant Extracts; Rats; Rats, Wistar; Skin; Skin Neoplasms

We previously reported that 6-shogaol strongly suppressed lipopolysaccharide-induced overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine macrophages. In this study, we further compared curcumin, 6-gingerol, and 6-shogaol's molecular mechanism of action and their anti-tumor properties. We demonstrate that topical application of 6-shogaol more effectively inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated transcription of iNOS and COX-2 mRNA expression in mouse skin than curcumin and 6-gingerol. Pretreatment with 6-shogaol has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-kappaB subunits. 6-Shogaol also reduced TPA-induced phosphorylation of IkappaBalpha and p65, and caused subsequent degradation of IkappaBalpha. Moreover, 6-shogaol markedly suppressed TPA-induced activation of extracellular signal-regulate kinase1/2, p38 mitogen-activated protein kinase, JNK1/2, and phosphatidylinositol 3-kinase/Akt, which are upstream of nuclear factor-kappaB and AP-1. Furthermore, 6-shogaol significantly inhibited 7,12-dimethylbenz[a]anthracene/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 wk. Presented data reveal for the first time that 6-shogaol is an effective anti-tumor agent that functions by down-regulating inflammatory iNOS and COX-2 gene expression in mouse skin. It is suggested that 6-shogaol is a novel functional agent capable of preventing inflammation-associated tumorigenesis.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Catechols; Curcumin; Cyclooxygenase 2; Dose-Response Relationship, Drug; Fatty Alcohols; Female; Gene Expression Regulation, Enzymologic; Mice; Mice, Inbred ICR; Nitric Oxide Synthase Type II; Papilloma; RNA, Messenger; Signal Transduction; Skin; Skin Neoplasms; Tumor Burden

The modulating effects of curcumin-free aqueous turmeric extract (CFATE), ethanolic turmeric extract (ETE) and turmeric (T) powder on the benzo(a)pyrene (B(a)P)-induced forestomach tumors were investigated in Swiss female albino mice receiving oral administration of B(a)P at a dose of 1 mg twice weekly for 4 weeks. Administration of 0.2%/1.0%/5.0% turmeric-derived CFATE as sole source of drinking water or 0.01%/0.05%/0.25% ETE in diet or 0.2%/1.0%/5.0% T in diet, 2 weeks before, during and 2 weeks after the last dose of B(a)P (during initiation period) resulted in significant suppression of B(a)P-induced tumorigenesis when compared with the group receiving B(a)P and control diet/drinking water. Among different fractions tested, CFATE appears to be more powerful as not only did it reduce the tumor multiplicity to the lowest levels but it also significantly reduced the tumor incidence. Administration of 5.0% turmeric-derived CFATE as the sole source of drinking water or 0.25% ETE/5.0% T in diet starting from 48 h after the last dose of B(a)P (during the post-initiation period) until the termination of the experiment, also inhibited the formation of multiple gastric tumors by B(a)P, although the suppression of tumor multiplicity was appreciably more in the groups that received 5.0% turmeric-derived CFATE/0.25% ETE treatment during initiation with carcinogen, i.e. 2 weeks before, during and 2 weeks after the last dose of B(a)P. The present data clearly indicate the potential of turmeric-derived CFATE as a powerful chemopreventive fraction and also demonstrate the efficacy of lower, i.e. 1/25th and/or 1/5th of the reported, chemopreventive doses of T/ETE (essentially curcumins) in inhibiting B(a)P-induced forestomach tumors in mice.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Benzo(a)pyrene; Carcinogens; Curcuma; Curcumin; Dose-Response Relationship, Drug; Female; Mice; Papilloma; Plant Extracts; Stomach Neoplasms

Five synthetic curcuminoids and three natural curcuminoids were investigated for their antimutagenic and anti-promotional activity. The natural curcuminoids, curcumin I (diferuloylmethane), curcumin II (feruloyl-p-hydroxycinnamoylmethane) and curcumin III (bis-(p-hydroxycinnamoyl)methane) isolated from Curcuma longa were found to be potent inhibitors of mutagenesis and crotean oil-induced tumour promotion. Curcumin III produced 87.6% inhibition to 2-acetamidofluorene (2-AAF) induced mutagenesis, at a concentration of 100 micrograms/plate, curcumin II and curcumin I produced 70.5% and 68.3% inhibition at the same concentration. All the synthetic curcuminoids were found to inhibit 2-AAF-induced mutagenicity among which salicyl- and anisylcurcuminoids were the most active. Curcumin III was the most effective anti-promotor among natural curcuminoids. While 90% of the control animals were having papillomas on the 10th week of tumour initiation, only 10% of the curcumin III-treated animals, 20% of the curcumin II-treated animals, and 40% of the curcumin I-treated animals were having papillomas. Salicylcurcuminoid, which was causing no papillomas by the 10th week, was the most potent anti-carcinogen among the synthetic curcuminoids. Piperonal curcuminoid also exhibited anti-promotional activity.

Topics: Animals; Anticarcinogenic Agents; Antimutagenic Agents; Curcumin; Female; Free Radical Scavengers; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Papilloma; Rats; Rats, Sprague-Dawley

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents, Phytogenic; Catechols; Curcumin; Male; Mice; Mice, Inbred Strains; Papilloma; Plant Extracts; Skin Neoplasms