• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3123-3129
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• 2013

Background: The search for naturally occurring agents in routinely consumed foods that may inhibit cancer development is of high priority. [6]-Paradol is a pungent phenolic bioactive component from ginger with welldocumented health promoting antioxidant, antimutagenic, antigenotoxic and anti-inflammatory properties. However, anticarcinogenic effects have yet to be fully explored. The objectives of the present study were therefore to assess protective effects against 7,12-dimethylbenz(a)anthracene (DMBA) induced buccal pouch carcinogenesis in male golden Syrian hamsters. Methods: Oral squamous cell carcinomas developed in the left buccal pouch of hamsters on painting with 0.5% of DMBA, three times in a week. To assess the apoptotic associated gene expressing potential of [6]-paradol, it was orally administered to DMBA treated hamsters on alternate days from DMBA painting for 14 weeks. Results: We observed 100% tumor formation with marked levels of neoplastic changes and altered the expression of apoptotic associated gene (p53, bcl-2, caspase-3 and TNF-${\alpha}$) was observed in the DMBA alone painted hamsters as compared to control hamsters. Oral administration of [6]-paradol at a dose of 30 mg/kg b.wt to DMBA treated animals on alternative days for 14 weeks significantly reduced the neoplastic changes and improved the status of apoptosis associated gene expression. Conclusion: These observations confirmed that [6]-paradol acts as a tumor suppressing agent against DMBA induced oral carcinogenesis. We also conclude that [6]-paradol also effectively enhances apoptosis- associated gene expression in DMBA treated animals.

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.181-188
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• 2007

Objectives : This study was to verify the Attributive Channel theory of herbal medicine. Methods : [13lI]iodocurcumin was synthesized, separated, and refined from curcumin, the major component of Curcuma species, followed by observing the biodistribution in an organism. Especially, from the fact that curcumin has shown to possess potent anti-carcinogenic properties, the biodistribution in the carcinogenesis organism was analyzed. Result : Iodocurcumin 23mg was obtained through column chromatography after a reaction with 50mg of Curcumin and ICl. The nominal yield of [13lI]iodocurcumin synthesis was 35% when checked with radioactive layer of chromatography. [13lI]iodocurcumin was most largely distributed in the stomach of a BALB/c mouse and a C57BL/6 mouse transplanted with Lewis lung carcinoma cell. Conclusion : The fact that [13lI]iodocurcumin was most largely distributed in the stomach was related with the Attributive Channel theory. And there was no significant finding related to tumor cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2575-2580
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• 2015

Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increasing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.101-110
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• 2018

In this study, we aimed to investigate the neuroprotective effects of caffeic acid phenethyl ester (CAPE), an active component of propolis purified from honeybee hives, on photothrombotic cortical ischemic injury in mice. Permanent focal ischemia was achieved in the medial frontal and somatosensory cortices of anesthetized male C57BL/6 mice by irradiation of the skull with cold light laser in combination with systemic administration of rose bengal. The animals were treated with CAPE (0.5-5 mg/kg, i.p.) twice 1 and 6 h after ischemic insult. CAPE significantly reduced the infarct size as well as the expression of tumor necrosis $factor-{\alpha}$, hypoxiainducible $factor-1{\alpha}$ monocyte chemoattractant protein-1, $interleukin-1{\alpha}$, and indoleamine 2,3-dioxygenase in the cerebral cortex ipsilateral to the photothrombosis. Moreover, it induced an increase in heme oxygenase-1 immunoreactivity and interleukin-10 expression. These results suggest that CAPE exerts a remarkable neuroprotective effect on ischemic brain injury via its anti-inflammatory properties, thereby providing a benefit to the therapy of cerebral infarction.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.29-35
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• 2019

Decursin is a major biological active component of Angelica gigas Nakai and is known to induce apoptosis of metastatic prostatic cancer cells. Recently, other reports have been commissioned to examine the anticancer activities of this plant. In this study, we evaluated the inhibitory activity and related mechanism of action of decursin against glioblastoma cell line. Decursin demonstrated cytotoxic effects on U87 and C6 glioma cells in a dose-dependent manner but not in primary glial cells. Additionally, decursin increased apoptotic bodies and phosphorylated JNK and p38 in U87 cells. Decursin also down-regulated Bcl-2 as well as cell cycle dependent proteins, CDK-4 and cyclin D1. Furthermore, decursin-induced apoptosis was dependent on the caspase activation in U87 cells. Taken together, our data provide the evidence that decursin induces apoptosis in glioblastoma cells, making it a potential candidate as a chemotherapeutic drug against brain tumor.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.4
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• pp.379-387
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• 2024

Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti-tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RT-qPCR and Western blotting were employed to examine the levels of HSP90, Snail, E-cadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth.

• Korean Journal of Pharmacognosy
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• v.47 no.3
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• pp.197-203
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• 2016

Decursin is a major component of the root of Angelica gigas(Umbelliferae), which has been traditionally used in Korea as a tonic and to treat anemia, hemiplegia, and women's diseases. The objective of this study is to identify the anti-cancer mechanism induced by decursin on apoptosis of human leukemia and lymphoma cells. Cytotoxicity of decursin on U937, HL-60, MOLT-4, THP-1 cells showed the significant effects. First of all, $IC_{50}$ of decursin on four cell lines was 27.1, 32.4, 17.4, $15.1{\mu}M$, respectively. So $IC_{50}$ in THP-1 cells was the smallest among 4 cell lines treated with decursin($15.1{\mu}M$). In order to understand the apoptosis-mechanism by decursin, we examined the gene expression of bcl-2(anti-apoptotic), bax(pro-apoptotic) and p53(tumor suppressor)after treating the THP-1 cells with decursin(10, 50 and $100{\mu}M$). It was found bcl-2 gene was decreased dose dependently, the expression level of bax gene of THP-1 cells treated with $100{\mu}M$ of decursin was about 3 times higher than those of control, and p53 gene was increased In the same concentration($100{\mu}M$), p53 gene was increased dose dependent manner. In protein express, bcl-2 and p53 protein showed a tendency to decrease. bax was increased about 4 fold. Therefore decursin is a useful chemotherapeutic agent against leukemia.

• Journal of Life Science
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• v.23 no.3
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• pp.355-360
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• 2013

Withaferin A is an active component of Withania somnifera, and has anti-inflammatory, anti-tumor, and immune modulatory effects. However, the effects of withaferin A on metalloproteinase (MMP)-9 expression and activity have not been investigated. In this study, we investigated the ability of withaferin A to inhibit MMP-9 expression and activity in PMA-treated human cervical carcinoma Caski cells. Withaferin A markedly inhibited the PMA-induced MMP-9 activity in a dose-dependent manner. Withaferin A decreased not only PMA-induced MMP-9 promoter activity but also PMA-mediated MMP-9 mRNA and protein expression in Caski cells. NF-${\kappa}B$ promoter activity, which is important in MMP-9 expression, was also decreased in combined treatment with withaferin A and PMA. Furthermore, withaferin A markedly suppressed the ability of PMA-mediated migration in Caski cells. Our findings suggest that withaferin A might inhibit PMA-induced migration through the down-regulation of MMP-9 expression and activity.

• Korean Journal of Pharmacognosy
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• v.49 no.4
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• pp.362-371
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• 2018

Hwanggeumjackyak-tang (HJT) composed of Scatellaria baicalensis Georgi, Paeonia Lactiflora and Glycyrrhizae uralensis Fischer is a traditional Korean herbal medicine widely used for acute enteritis. In order to develop the tablet formulation of HJT, evaluation of the flow properties, thickness, diameter, hardness, friability and disintegration was carried out on four HJT granules according to mixed content of seven additives. Simultaneous analysis used HPLC method was performed of HJT tablet and was determined of the seven marker components; Albiflorin, Paeoniflorin, Liquiritin, Baicalin, Baicalein, Glycyrrhizic acid and Wogonin. The biological activities were examined the effect of HJT on anti-oxidation and pro-inflammation mediated by LPS-stimulation. We confirmed that both of HJT-Decoction (HJT-D) and HJT-Formulation (HJT-F) have the similar contents on total polyphenol and flavonoid and inhibited the secretion of nitro oxide (NO), interleukin $(IL)-1{\beta}$,interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$ and the expression of nitric oxide synthase (iNOS), $IL-1{\beta}$, IL-6, $TNF-{\alpha}$. Therefore, the developed formulation for tablet of HJT would provide chemically and biologically the same effect compared with decoction of HJT.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.216-221
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• 2019

The c-Met protein is a receptor tyrosine kinase involved in cell growth, proliferation, survival, and angiogenesis of several human tumors. Overexpression of c-Met has been found in gastric cancers and correlated with a poor prognosis. Indirubin is the active component of Danggui Longhui Wan, which is a traditional Chinese antileukemic recipe. In the present study, we tested the anti-cancer effects of an indirubin derivative, LDD-1937, on human gastric cancer cells SNU-638. When we performed the in vitro kinase assay against the c-Met activity, LDD-1937 inhibited the activity of c-Met. This result was confirmed by immunoblot and immunofluorescence of phosphorylated c-Met. Immunoblot analysis showed that LDD-1937 decreased the expression of the Erk1/2, STAT3, STAT5, and Akt, downstream proteins of c-Met. In addition, LDD-1937 reduced the cell viability and suppressed colony formation and migration of SNU-638 cells. Furthermore, LDD-1937 induced $G_2/M$ phase arrest in the SNU-638 cells by decreasing the expression levels of cyclin B1 and CDC2. Cleaved-PARP, an apoptosis-related protein, was up-regulated in cells treated with LDD-1937. Overall, this study suggests that LDD-1937 may be a novel small-molecule with therapeutic potential for selectively inhibiting c-Met and c-Met downstream pathways in human gastric cancers overexpressing c-Met.