• Nutritional Sciences
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• v.9 no.3
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• pp.212-226
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• 2006

The involvement of arachidonic acid (AA) metabolizing enzyme, lipoxygenase (LOX), in the development of particular tumors in humans has gradually been acknowledged and LOX has emerged as a novel target to prevent or treat human cancers. In the mouse skin carcinogenesis model, which provides an excellent model to study multistage nature of human cancer development, many studies have shown that some of the LOXs are constitutively upregulated in their expression. Moreover, application of LOX inhibitors effectively reduced tumor burdens, which implicates the involvement of LOX in mouse skin tumor development as well. 8S-LOX is a recently cloned LOX, which is specifically expressed in mouse skin after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment but not in normal skin. Unlike other members of the LOX 'family' expressed in mouse skin, this TPA-induced expression of 8S-LOX is prominent only in the skin of the TPA tumor promotion-sensitive strains of mice (SENCAR, CD-1, and NMRI) but not in the promotion-resistant C57BL/6J mice. This is a very unique phenomenon among strains of mice. Constitutive upregulation of 8S-LOX was also found in early stage papillomas and the expression was gradually reduced as the tumors became malignant. Based on these observations, it has been thought that 8S-LOX is involved in TPA-induced tumor promotion as well as in tumor conversion from papillomas to carcinomas. In accordance with this hypothesis, several studies have suggested possible roles of 8S-hydroxyeicosatetraenoic acid (HETE), an AA metabolite of 8S-LOX, in mouse skin tumor development. A clastogenic activity of 8S-HETE was demonstrated in primary keratinocytes and a close correlation between the levels of etheno-DNA adducts and 8S-HETE during skin carcinogenesis was also reported. On the other hand, it has been reported that 8S-LOX protein expression is restricted to a differentiated keratinocyte compartment Moreover, reported findings on the ability of 8S-HETE to cause keratinocyte differentiation appear to be contrary to the procarcinogenic features of the 8S-LOX expression, presenting a question as to the role of 8S-LOX during mouse skin carcinogenesis. In this review, molecular and biological features of 8S-LOX as well as current views on the functional role of 8S-LOX/8S-HETE during mouse skin carcinogenesis are presented.

• Archives of Plastic Surgery
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• v.38 no.4
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• pp.339-344
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• 2011

Purpose: The goal of cancer surgery is complete removal of cancer tissue and prevention of recurrence. Surgeons can change the surgical instruments after total resection of the cancer mass. The purpose of this procedure is to prevent dissemination of the cancer cells attached to the surgical instruments. Authors hypothesize the possibility of local recurrence caused by the cancer cells attached to the surgical instruments in the skin cancer cases. Methods: Skin cancers were induced by using DMBA-TPA two-stage carcinogenesis model in 10 of Balb/c mice. In 2-weeks, skin cancer was developed in all 10 mice. cancer cell attached surgical instruments were made by pinching the removed cancer tissue using Adson tissue forcep 10, 20, 30 times each. To count number of cancer cells in each forcep with different number of pinching was done, the forceps were washed in 30 mL of the normal saline and Cytospin preparation was done. To make recurrence models from cancer cell attached surgical instrument, three incisions were made in normal skin of each mouse, and local seeding was done by pinching subcutaneous tissue in 10, 20, 30 times each by using Adson teeth forceps mentioned above as cancer cell attached surgical instrument. Results: All skin cancers were squamous cell carcinoma. Local recurrences were developed in 7 mice (3 in 10 times forceping site, 2 in 20 times forceping and 3 in 30 times forceping). In the cytospin test, the mean number of squamous cells in 100 microscope was 28.6 in 10 times, 47.2 in 20 times, 93.6 in 30 times, respectively. P value was 0.002 in Wilcoxon-Sign test. Conclusion: The number of cell count was significantly increased as number of pinching was increased. And these cells are able to induce local recurrence by local seeding. Considering this result, authors are able to confirm that the minimal handling in cancer surgery is important factor to prevent local recurrence.

• Journal of Environmental Health Sciences
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• v.32 no.5 s.92
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• pp.492-498
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• 2006

Ultraviolet(UV) radiation causes a variety of biological effects on the skin, including inflammation, pigmentation, photoaging and cancer. Free radicals are involved in inflammatory skin reactions induced by UVB radiation. In this study, we investigated the effects of antioxidants(Tea, Korean red ginseng, Ginkgo biloba extract) on UVB-induced skin damage. Tea, KRG and EGb 761 were topically treated to dorsal skin of ICR mouse. The mice were also treated soon after IMED ($1.4KJ/m^{2}$) of UVB irradiation. Skin pigmentation of irradiated mouse was observed by a chromameter after 2 weeks. Topical application of Tea, KRG and EGb 761 for 2 weeks decreased skin pigmentation compared to DVB control group(p<.05). Tea, KRG and EGb 761 also reduced UVB-induced infiltration of inflammatory cells. These results showed that Tea, KRG and EGb 761 as a topical application may have preventive effect against UVB-induced skin damage.

• Nutrition Research and Practice
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• v.7 no.6
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• pp.439-445
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• 2013

It has been shown that dysregulation of IGF-1 signaling is associated with tumor incidence and progression, whereas blockade of the signaling can effectively inhibit carcinogenesis. Although several mechanisms of anticancer activity of quercetin were proposed, molecular targets of quercetin have not been identified yet. Hence, we assessed the effect of quercetin on IGF-1 signaling inhibition in BK5.IGF-1 transgenic (Tg) mice, which over-expresses IGF-1 in the skin epidermis. A quercetin diet (0.02% wt/wt) for 20 weeks remarkably delayed the incidence of skin tumor by 2 weeks and reduced tumor multiplicity by 35% in a 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two stage mouse skin carcinogenesis protocol. Moreover, skin hyperplasia in Tg mice was significantly inhibited by a quercetin supplementation. Further analysis of the MT1/2 skin papilloma cell line showed that a quercetin treatment dose dependently suppressed IGF-1 induced phosphorylation of the IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1, Akt and S6K; however, had no effect on the phosphorylation of PTEN. Additionally, the quercetin treatment inhibited IGF-1 stimulated cell proliferation in a dose dependent manner. Taken together, these data suggest that quercetin has a potent anticancer activity through the inhibition of IGF-1 signaling.

• The Korean Journal of Food And Nutrition
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• v.13 no.5
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• pp.411-418
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• 2000

The purpose of this study was to investigate effects of chestnut inner skin tea, brown rice-green tea and Cassia lora tea on the activation of physiological functions (regional cerebral blood flow, mean arterial blood pressure, proliferation of immunocytes in vitro and in vitro, suppression of cancer cell proliferation) in mouse and rat. We used 8 weeks-old balb/c male mice, 300g ICR rats and L1210 cell lines. Regional cerebral blood flow(rCBF) and mean arterial blood pressure(BP) were measured using Leser-Doppler Flowmetry(LDF) and the proliferation of cells was measured using a colorimetric tetrazolium assay(MTT assay). The experimental results are as follows : 1. rCBF was increased by Cassia tora tea, but decreased by chestnut inner skin tea in rats. 2. BP was increased by brown rice-green tea in rats. 3. Proliferation of mouse thymocytes and splenocytes were significantly increased by chestnut inner skin tea in vitro. 4. Proliferation of mouse thymocytes was decreased by Cassia tora tea and brown rice-green tea in vitro. 5. Proliferation of mouse thymocytes was decreased by Cassia tora tea and brown rice-green tea in L1210 transplanted mice. 6. Proliferation of splenocytes was accelerated by chestnut inner skin tea in L1210 transplanted mice. 7. Proliferation of L1210 cells was inhibited by chestnut inner skin tea and Cassia tora tea in L1210 transplanted mice.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4655-4660
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• 2012

Opuntia humifusa, member of the Cactaceae family, was previously demonstrated to have radical scavenging, anti-inflammatory and anti-proliferative effects in in vitro models. It was suggested that O. humifusa could function in the prevention of carcinogenesis. To investigate the in vivo chemopreventive effect of O. humifusa, mice were fed a diet containing either 1% or 3% following 7, 12-dimethylbenz[a] anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induction of skin carcinogenesis. Significant decrease in the numbers of papilloma and epidermal hyperplasia were observed in mice fed with O. humifusa, compared to the control group. O. humifusa also upregulated high total antioxidant capacity and level of phase II detoxifying enzyme such as superoxide dismutase and glutathione S-transferase activity in the skin. Lipid peroxidation activity level was measured in skin cytosol and significantly inhibited in 3% OH fed group compared to the control group. These results suggest that O. humifusa exerts chemopreventive effects on chemical carcinogenesis in mouse skin and that prevention effects are associated with reduction of oxidative stress via the modulation of cutaneous lipid peroxidation, enhancing of total antioxidant capacity especially in phase II detoxifying enzyme system and partial apoptotic influence.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.115-115
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• 1997

A new capsaicin analog modified with 4-hydroxyl and alkyl chain of capsaicin was a very potent antiinflammatory analgesic drug and may be clinically useful for those who have rheumatoid arthritis, diabetic neuropathy and cancer. The purpose of this study was to investigate histopathology after short and long term application of poloxamer-based gels, and percutaneous absorption of various topical formulations. Poloxamer-based gel was prepared by cold method using poloxamer 407. The poloxamer gels was applied to dorsal sites of hairless mouse skin during one week or one month for the evaluation of skin irritation. The applied site was then sectioned for histopathologic examination. The topical formulations were also prepared using CMC, HPMC, MC, carbopol and glycerylmono stearate. Skin variation of poloxamer gels was studied using excised hairless mouse, rat, hamster and human penis skin. Franz-type diffusion cells were used far skin penetration of drug against receptor phase filled with about 10$m\ell$ of 0.9% saline solution kept at 32$^{\circ}C$. The concentration of drug was determined by the reverse phased C18, Symmetry HPLC with fluorometeric detector. No skin erythema was observed after dorsal application of poloxamer-based gels for one week or one month. No histopathologic changes was also examined, suggesting no skin toxicity of poloxamer-based gels. The order of flux rate was HPMC > MC ( CMC > poloxamer >> glycerylmono stearate ( carbopol. There was a skin variation of poloxamer gels. The flux rate of poloxamer gels was highest in case of hairless mouse followed by rat, human and hamster skin. The Partial support-Ministry of Science and Engineering (HAN project).

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.105.1-105.1
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• 2003

The purpose of this study is to investigate the biological effects in black mouse by neutron irradiation at HANARO reactor in KAERI. Neutrons readily penetrate the charged field of an atomic nucleus because they are electrically neural. And so it can fight cancer with the radiation released when an atom of the element boron absorbs a neutron. The main patient in BNCT facility is brain cancer and sometimes skin cancer in foreign countries until now. Therefore, mice were laid flat and so irradiated at the direction of the front. (omitted)

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.4
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• pp.462-470
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• 2012

Mountain cultivated ginseng (MCG) is a type of Panax ginseng C. A. Mayer, grown in the mountains by artificial seeding. In general, it has been known that the biophysical activities of MCG is greater than that of ginseng. However, the in vivo efficacy of MCG on cancer has not been studied. In this study, we investigated the anti-carcinogenic effect of MCG and ginseng using the 7,12-dimethylbenz[a]anthracene (DMBA)-12-O-tetradecanoylphorbol- 13-acetate (TPA) two stage mouse skin carcinogenesis model. Six weeks of female ICR mice were divided into control, MCG, and ginseng diet groups and were subjected into two different experimental protocols. In the first study, each experimental diet was fed with TPA promotion for 24 weeks. The result showed that supplementation of MCG reduced tumor incidence, tumor multiplicity, and tumor size compared to those of the control and ginseng groups. In the second study, 3 groups of mice were supplied with each diet 4 weeks before DMBA tumor initiation, until the end of experiment. The result showed that tumor incidence, tumor multiplicity, and tumor size were reduced in the ginseng diet group compared to those of the control and MCG groups. TPA-induced BrdU incorporation was also significantly reduced in the ginseng diet group. Taken together, these results suggest that MCG is chemotherapeutic, whereas ginseng has a chemopreventative effect on mouse skin cancer.

• Preventive Nutrition and Food Science
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• v.16 no.4
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• pp.283-290
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• 2011

The recent increase of colon, breast, and prostate cancer incidence in Korea has been attributed to a diet pattern change to a more Western style, in which the foods eaten are higher in protein and fat. Whether high protein intake itself stimulates tumor cell growth and exacerbates disease status has been investigated, however, many epidemiological studies have inconsistent results between meat intake and the risk of certain cancers. These inconsistent results are partly because of the difficulty of studying the effects of just the meat intake. Other factors, such as overall meal context, could not be completely excluded in the study. To address the question of whether high protein itself is independently associated with carcinogenesis, we initiated ICR mice with 200 nmol ($50{\mu}g$) 7,12-dimethylbenz[a]anthracene (DMBA) and fed animals either a normal diet (ND, 14% casein) or a high protein diet (HPD, 50% casein) for 15 weeks with 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in two-stage skin carcinogenesis protocol. There was no significant difference between ND and HPD group in food intake and body weight throughout the experiment. However, tumor multiplicity of the HPD group was decreased by 75.5% compared to that of the ND group. In addition, HPD inhibited skin hyperplasia and epidermal cell proliferation. Western analyses with whole skin lysates showed that HPD inhibited TPA-induced Akt (S473), S6K (T389), 4E-BP1 (Thr 37/46) and Erk1/2 (Thr202/Tyr204) phosphorylation as well as COX-2 expression. Taken together, these data suggest that a high protein diet has an anticarcinogenic effect by inhibiting the TPA-induced Akt signaling pathway.