• The Korean Journal of Zoology
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• v.39 no.3
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• pp.266-272
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• 1996

Experiments were carried out to ascertain whether gonadotropin or a phorbol ester (12-O-tetradecanoyl phorbol-13-acetate, TPA) induces oocyte ovulation and stimulates prostaglandin synthesis by Rana ovarian follicles in vitro. Rana nigromaculata collected from underground in spring were utilized for the present experiment. Treatment of frog pituitary homogenate (FPH) or TPA to ovarian fragments in culture induced oocyte ovulation in a dose dependent manner and stimulated prostaglandin F2a (PGF$_2$$\alpha$ synthesis. Both treatruents were more effective in inducing the ovulation and PGF$_2$$\alpha$ secretion by the follicles obtained in May than those in April. A Protein kinase C inactivator, 1-(5-isoquinolinyl-sulfonyl)-2-methyl-piperazine (H-7), or cyclooxygenase inhibitor, indomethacin (IM) suppressed the FPH- or TPA-induced PGF$_2$$\alpha$ production, but IM failed to suppress the FPH- or TPA-induced ovulation. Time course of oocyte ovulation and PGF$_2$$\alpha$ secretion by FPH and TPA treatments were very similar to each other. FPH stimulated progesterone secretion by the follicle but TPA failed to do so. Taken together, the data presented here suggest that protein kinase C (PKC) in follicle play a role in the ovulation process of Rana nigromaculata, probably via prostaglandin synthesis.

• Journal of Life Science
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• v.22 no.7
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• pp.964-969
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• 2012

Genistein, a predominant isoflavone, has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. In the present study, we investigated the effects of genistein on the activity and the expression of matrix metalloproteinases (MMPs) in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Our findings showed that MMP-9 and -2 activation was significantly increased in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). However, the increased activities of MMP-9 and -2 in TPA-treated cells were concentration-dependently inhibited by treatment with genistein, and this was also correlated with a decrease in the expression of their mRNA and proteins. In addition, a matrigel invasion assay showed that genistein reduced TPA-induced invasion of MCF-7 and MDA-MB-231 cells. Although further in vivo studies are needed, these results suggest that genistein treatment may inhibit tumor cell invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2973-2978
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• 2013

Maesil (Prunus mume Siebold & Zucc.), a member of the genus Rosaceae, has been reported to have antioxidative effects, as well as anticancer influence in many cancer lines. Thus, this present study was designed to investigate the inhibitory effect of fermented Maesil with probiotics against 7,12-dimethylbenz[a]anthracene (DMBA), 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced mouse skin carcinogenesis via its antioxidative potential. Mice were fed a diet containing fermented Maesil, containing either 1% (1% FM fed group) or 2% (2% FM fed group) along with probiotics following DMBA and TPA exposure. Continuous ingestion of the experimental feed markedly inhibited skin carcinogenesis, as evidenced by a marked decrease in papilloma numbers and epidermal hyperplasia as well as cellular proliferation and the percentage of proliferating-cell nuclear antigen positive cells. Also, the FM fed group showed an increase of total antioxidant capacity as well as an increased level of phase II detoxifying enzymes such as superoxide dismutase, concurrent with a decreased lipid peroxidation activity level. Taken together, these results suggest that fermented Maesil has the ability to suppress the development of DMBA-TPA induced skin carcinogenesis, via the reduction of lipid peroxidation, enhancing total antioxidant capacity and phase II detoxifying enzyme.

• Journal of Environmental Health Sciences
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• v.19 no.3
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• pp.64-73
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• 1993

The study was conducted to investigate the mechanism of tumor promotion as the time courses and the doses of promoter, and the effect of plant fiavonoids on the TPA-induced ODC responses. The results are summarized as follows: 1. A single, toppical application of 17 nmole of the potent tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate, resulted in an induction of mouse epidermal Ornithine Decarboxylase with a peak at 5 hours after treatment and maximized 5.1 times as large as ODC activities of control. 2. Dose-response curve indicated that the tumor promotion increases proportionally between 1.7 and 170 nmole of TPA. This dose dependency relationship indicated that the ability of TPA to stimulate ODC is linked its ability to promote tumors. 3. Naturally occurring plant fiavonoids with anticarcinogenic and antipromotional activities were tested for their abilities to inhibit ODC response induced by skin tumor promoter TPA. Intra peritoneal administration of fiavonoids compounds (rutin, naphthofiavone, baicalein, quercitrin) and herbal drugs (sophorae rios, crataegi fructus, armeniacae semen) inhibited 17 nmole TPA-induced ODC activities in mouse epidermis in vivo.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.123-123
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• 2003

Primary cultures of rat fetus brain exhibit phenotypes of neuron, oligodendrocyte, and astrocyte from "neurospheres". To understand the role of mitogen-activated protein kinase (MAPK) cascade and gap junctional intercellular communication (GJIC) in the differentiation of neurosphere-derived astrocyte, we investigated the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the cultured astrocyte morphology.(omitted)

• Environmental Mutagens and Carcinogens
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• v.25 no.2
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• pp.66-70
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• 2005

Telomerase, a specialized RNA-directed DNA polymerase that extends telomeres of eukaryotic chromosomes, has activity in most malignant tumors and provides a mechanism for the unlimited potential for division of neoplastic cells. Although telomerase is known to be a regulated enzyme, the factors and mechanisms involved in telomerase regulation are not well understood. In the present study, we compared the effect of 12-O­tetradecanoyl-phorbol-13-acetate (TPA) and non-phorbol ester tumor promoters such as okadaic acid, anthralin and benzoyl peroxide on the expression of telomerase in the mouse skin carcinogenesis system, a well characterized model for studying pre-malignant and malignant progression. We found that most early papillomas harvested after 10 weeks of TPA promotion showed telomerase activity. Other papillomas harvested after 10 weeks of okadaic acid, anthralin and benzoyl peroxide promotion and after single treatment of DMBA only also showed telomerase activity, respectively. On the other hand, normal and all skins surrounded by papillomas harvested after 10 weeks of these promoters has no telomerase activity. Taken together these results, there appears to be no clear association between the level of telomerase activity and protein phosphorylation in mouse skin papillomas and telomerase may be useful as bio-markers in early detection of tumors.

• The Journal of the Korean dental association
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• v.37 no.7 s.362
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• pp.517-529
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• 1999

본 연구는 태령 19일된 백서 태자 두 개관에서 분리한 골모세포유사세포에 화학발암물질인 7,12-Dimethylbenz(a)anthracene (DMBA: 0.5 ㎍/ml) 및 tumor promotor인 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 1.0 ㎍/ml)를 단독 혹은 복합 처리하여 PTRCC-DMBA, RCC-DMBA 및 RCC-DMBA-TPA 세포주를 확립시키고, 각 세포의 세포형태, 세포성장곡선, alkaline phosphatase와 acid phosphatase 활성 및 in vitro tumorigenicity를 연구하였다. 또한 c-myc, c-랜, c-jun, p53 및 Rb 유전자의 발현변화와 항암단백질인 p53 및 pRb 단백질의 발현변화를 관찰하여 골모세포유사세포가 악성형질전환되는 분자기전의 일단을 연구하고자 시행하였다. 본 실험에 사용한 모든 세포군에서 높은 aikaline phosphatase 활성과 낮은 acid phosphatase/alkaline phosphatase ratio를 보여 골모세포의 특성을 나타내었다. RCC-DMBA와 RCC-DMBA-TPA 세포는 정상세포나 PTRCC-DMBA에 비해 빠른 성장속도를 보였으며, 또한 SOFT AGAR상에서 colony를 형성하여 anchorage-independent growth를 나타내었다. 화학발암 물질로 악성변형된 세포들은 정상세포나 PTRCC-DMBA 세포에 비해 c-myc 유전자의 과발현이 관찰되었다. 정상세포에서 p53 유전자의 발현은 1.9 kb의 message만이 발현되었다. 그러나 화학발암물질로 형질전환된 세포에서는 1.9 kb message외에도 1.6 kb의 message가 더 발현되었으며, message의 양도 현저히 증가되었다. p53 단백질의 발현은 RCC-DMBA-TPA 세포에서 정상세포에 비해 현저히 감소하였으나, RCC-DMBA 세포에서는 유사한 경향을 보였다. Rb 유전자의 발현은 RCC-DMBA-TPA 세포에서만 현저히 감소하였으나, Rb 단백질의 발현은 정상세포에 비해 형질전환된 세포들에서 모두 현저히 감소되었고, 특히 RCC-DMBA-TPA 세포에서는 거의 발현되지 않았다. 이상의 결과에서 백서 태자 두 개관에서 분리한 골모세포유사세포는 화학발암물질인 DMBA에 의해 악성형질전환이 유도되었으며, c-myc의 과발현 및 p53과 Rb 단백질의 발현감소가 정상 골모세포유사세포의 악성변형과정에 밀접히 연관되어 있음을 시사한다.

• Journal of Microbiology and Biotechnology
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• v.30 no.3
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• pp.325-332
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• 2020

Methyl linderone (ML), a cyclo-pentenedione, was isolated from the fruit of Lindera erythrocarpa Makino (family Lauraceae). This plant has well-known anti-inflammatory effects; however, the anti-cancer effects of ML have not yet been reported. Thus, in the present study we investigated the effects of ML on the metastasis of human breast cancer cells. We used 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated MCF-7 cells as the cell model to study the effects of ML on invasion and migration. ML was found to reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Moreover, it inhibited two metastasis-related factors, matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8), at the mRNA and protein expression levels, in TPA-treated MCF-7 cells. The mechanism by which ML exerted these effects was through the inhibition of translocation of activator protein-1 (AP-1) and signal transducer and activator of transcription-3 (STAT3), mediated via phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, our findings indicated that ML attenuated the TPA-stimulated invasion and migration of MCF-7 cells by suppressing the phosphorylation of ERK and its downstream factors, AP-1 and STAT3. Therefore, ML is a potential agent for the treatment of breast cancer metastasis.

• BMB Reports
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• v.46 no.11
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• pp.533-538
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• 2013

The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy- 3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-${\kappa}B$ activation in TPA-treated MCF-7 cells. However, BVT948 didn't block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9.

• 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.