• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.465-472
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• 2020

Colorectal cancer (CRC) is one of the most malignant type of cancers and its incidence is steadily increasing, due to life style factors that include western diet. Abnormal activation of canonical Wnt/β-catenin signaling pathway plays an important role in colorectal carcinogenesis. Therefore, targeting Wnt/β-catenin signaling has been considered a crucial strategy in the discovery of small molecules for CRC. In the present study, we found that Nodosin, an ent-kaurene diterpenoid isolated from Isodon serra, effectively inhibits the proliferation of human colon cancer HCT116 cells. Mechanistically, Nodosin effectively inhibited the overactivated transcriptional activity of β-catenin/T-cell factor (TCF) determined by Wnt/β-catenin reporter gene assay in HEK293 and HCT116 cells. The expression of Wnt/β-catenin target genes such as Axin2, cyclin D1, and survivin were also suppressed by Nodosin in HCT116 cells. Further study revealed that a longer exposure of Nodosin induced the G₂/M phase cell cycle arrest and subsequently apoptosis in HCT116 cells. These findings suggest that the anti-proliferative activity of Nodosin in colorectal cancer cells might in part be associated with the regulation of Wnt/β-catenin signaling pathway.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.627-634
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• 2024

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2307-2312
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• 2015

Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/ kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.918-922
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• 2016

The objective of this study was to determine the antioxidant and anti-proliferative activities of methanol, ethanol, acetone, and ethyl acetate extracts from oats (Avena sativa L.). Total polyphenol contents of extracts were analyzed by Folin-Ciocalteu assay. The antioxidant activities of extracts were determined by 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities and reducing power. The anti-proliferative activities of colon (HCT116), lung (NCI-H460), and breast (MCF7) cancer cells were investigated. Among solvents, methanol extract showed the highest amount of total polyphenols, which was 8.2 mg gallic acid equivalents/g residue. High levels of ABTS radical [12.1 mg Trolox equivalent antioxidant capacity (TEAC)/g residue] and DPPH radical (4.4 mg TEAC/g residue) scavenging activity and reducing power ($A_{700}=0.39$) were found in methanol extracts. Moreover, methanol extracts indicated higher anti-proliferative activities against HCT116 (69.5%), NCI-H460 (75.2%), and MCF7 (84.8%) cells compared with other extracts. The results show that methanol was the best solvent for extraction of antioxidant and anti-proliferative compounds from oats. Moreover, notable antioxidant and anti-proliferative activities of oats could have significant health benefits.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1147-1152
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• 2004

To investigate the anti-cancer effects of aqueous extract of Cheonkumwikyung-tang (CKWKT) on the growth of human lung carcinoma cell line A549, we performed various biochemical experiments such as the effects of CKWKT on the cell proliferation and viability, the morphological changes, the effects on expression of apoptosis and cell growth-regulatory gene products. Results obtained are as follow; CKWKT treatment declined the cell viability and proliferation of A549 cells in a concentration-dependent manner. The anti-proliferative effect by CKWKT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. CKWKT treatment induced apoptotic cell death of A549 cells in a concentration-dependent manner, which was associated with inhibition and/or degradation of apoptotic target proteins such poly(ADP-ribose) polymerase, β-catenin and phospholipase C-γ1. Western blot analysis revealed that the levels cyclin-dependent kinase inhibitor p21 expression were induced by CKWKT treatment in A549 cells. Taken together, these findings suggest that CKWKT-induced inhibition of human lung cancer cell proliferation is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products and CKWKT may have therapeutic potential in human lung cancer.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.151-156
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• 2003

We investigated the anti-proliferative effects of luteolin and apigenin, isolated from Ixeris sonchifolia Hance, on HepG2 human hepatocellular carcinoma cells. In MTT assay luteolin showed more efficient anti-proliferative effects on cells than apigenin did. According to propidium iodide staining and flow cytometry studies, we postulated that these effects might be a result of cell cycle arrest. Hence we examined the changes of protein expressions related to cell cycle arrest. Western blotting data demonstrated that the down-regulated expression of CDK4 was correlated to the increase of p53 and CDK inhibitor $p21^{WAF1/CIP1}$ protein. These data suggest that luteolin may have potential as an anti-cancer agent.

• Advances in Traditional Medicine
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• v.4 no.2
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• pp.91-94
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• 2004

Water and chloroform/methanol extracts of the three local Malaysian snakehead fish, Channa striatus (striped snakehead), Channa micropeltes (giant snakehead) and Channa lucius (blotched snakehead) were evaluated for inhibitory activity in chronic inflammation, using cotton pellet granuloma test. Both water extracts of C. striatus and C. micropeltes showed marked inhibition of the transudative and proliferative components of chronic inflammation (42.9 and 31.2% respectively for C. striatus, 35.6 and 26.2% for C. micropeltes) when compared to those of mefenamic acid (25.1 and 21.3% respectively) and piroxicam (36.1 and 26.2% respectively). The chloroform/methanol extracts did not exhibit any anti-inflammatory effects. These results indicated that C. striatus has more anti-transudative and anti-proliferative activities than the extract of C. micropletes. C. lucius extract in contrast, did not inhibit these two components. This present study indicated the beneficial effects of the water extracts of C. striatus and C. micropeltes, but not C. lucius on chronic inflammation.

• Food Science and Preservation
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• v.18 no.4
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• pp.590-596
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• 2011

Pimpinella brachycarpa, called as cham-na-mul in Korea, is an edible popular herb. However, the study of biological activity of P. brachycarpa is still rudimentary in worldwide. In this study, from the cultivated P. brachycarpa, we prepared the methanol extract and its subsequent solvent fractions, and their antimicrobial, antioxidation, and anti-proliferative activities were evaluated. The fraction yields of n-hexane (H), methylene chloride (EC), ethylacetate (EA), butanol (B), and water residue (W) from the methanol extract were 18.71, 0.7, 0.56, 4.57, and 71.51%, respectively. Analysis of total flavonoid and total polyphenol showed that the EA fraction contained the highest contents (89.23 and 200 mg/g), and the W residue has the lowest contents (19.6 and 2.27 mg/g) among the factions. In antimicrobial activity assay, the EA fraction showed a broad-range antibacterial activity, while the H fraction is effective against gram positive bacteria. In antioxidation activity assay, EA and B fraction showed strong DPPH anion and ABTS cation scavenging activities including reducing power, and Hand MC fraction showed effective nitrite scavenging activity (71.43~83.82 ${\mu}g$/mL of $IC_{50}$). In a while, only B fraction showed strong anti-proliferative activity against human colorectal cancer HCT-116 (166 ${\mu}g$/mL of $IC_{50}$) as a dose-dependent manner up to 200 ${\mu}g$/mL. These results suggest that the EA and B fraction of P. brachycarpa could be developed as functional food ingredients.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1250-1255
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• 2008

Onchungeum(OCE), a herbal formula, has been used for treatment of anemia, discharging blood and skin diseases. In the previous study, we investigated the anti-cancer effect of OCE by G1 arrest of the cell cycle in human hepatocarcinoma cells, Hep3B cells. In this study, it was examined that the difference of anti-proliferative mechanisms by change in the ratio of OCE composition (OCE I) in Hep3B cells. Treatment of OCE I exhibited a relatively strong anti-proliferative activity and caused various morphological changes such as membrane shrinkage and cell floating. In addition, OCE-I arrests the cell cycle at G1 phase, which was associated with the down-regulation of cyclin D1 and Cdk6 expressions. The G1 arrest was also associated with the induction of Cdk inhibitors p27 and p21. Moreover, both p21 and p27 were detected by immunoprecipitation with anti-Cdk4 and anti-Cdk2 antibodies in OCE I-treated cells but in case of OCE, p21 did not make any complexes with Cdk4 and Cdk2. These results suggest that the change in the ratio of OCE composition might induce different mechanisms in anti-cancer efficacy of OCE, which may confer characteristic principles in oriental medical formula.

• Natural Product Sciences
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• v.23 no.4
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• pp.258-264
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• 2017

This study analyzed the seeds of Zizyphus jujuba var. inermis commonly used as a remedy in traditional Chinese medicine, in order to determine its various biologically active compounds. Through process 3-pentadecylcatechol, ${\rho}$-menth-8-ene, and ${\gamma}$-bisabolene were isolated and identified for the first time which are urushiol, monoterpenoidal, and sesquiterpenoidal compounds, respectively. Also, found were another sesquiterpenoidal compounds, vomifoliol, and four steroidal compounds, ${\beta}$-sitosterol, stigmasterol, stigmasta-5,23-dien-$3{\beta}$-ol, and stigmast-4-en-3-one. In addition, fourteen triterpenoidal compounds were isolated and identified. These were lupeol, betulinic acid, betulinaldehyde, alphitolic acid, 3-O-cis-${\rho}$-coumaroyl-alphitolic acid, 3-O-trans-${\rho}$-coumaroyl-alphitolic acid, 2-O-cis-${\rho}$-coumaroyl-alphitolic acid, 2-O-trans-${\rho}$-coumaroyl-alphitolic acid, zizyberanalic acid, ceanothic acid, oleanolic acid, maslinic acid, 3-O-cis-${\rho}$-coumaroyl-maslinic acid, and 3-O-trans-${\rho}$-coumaroyl-maslinic acid. The structures were identified by comparing of the spectroscopic experiments, NMR and MS, and then compared that reported data, respectively. Three extracts of water, methanol, and chloroform from the seeds showed a weak anti-proliferative effect, anti-microbial activity, and anti-oxidant effect, respectively.