• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.88-92
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• 2006

Genistein was tested for chemopreventive potential against breast cancer by measuring the effect on proliferation of human breast cancer cells, human placental aromatase activity and cyclooxygenases-2 (COX-2) expression and activity, Genistein inhibited the growth of estrogen-independent MDA-MB-231 human breast cancer cell. However, there is no inhibitory effect of genistein on human placental aromatase activity. The expression of COX-2 was inhibited by genistein in Western blot analysis. Genistein significantly inhibited COX-2 activity at the concentrations of 10 (p<0.05), 25 (p<0.05) and 50 ${\mu}M$ (p<0.01). These results suggest that genistein may have breast cancer chemopreventive potential by inhibiting the growth of human breast cancer cell and expression and activity of COX-2.

• Archives of Pharmacal Research
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• v.28 no.1
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• pp.28-33
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• 2005

Seven diterpenes, four polyacetylenes, a lipid glycerol, and two sterols were isolated from the methylene chloride fraction of the root of Aralia cordata. Their chemical structures were determined as (-)-pimara-8(14), 15-dien-19-oic acid (2), pimaric acid (3), (-)-kaur-16-en-19-oic acid (4), 17-hydroxy-ent-kaur-15-en-19-oic acid (9), $7{\alpha}$-hydroxy-(-)-pimara-8(14), 15-dien-19-oic acid (10), $16\alpha$, 17 -dihydroxy-(-)-kauran-19-oic acid (11), 16-hydroxy-17-isovaleroyloxy-ent-kauran-19­oic acid (12), falcarindiol (5), dehydrofalcarindiol (6), dehydrofalcarindiol-8-acetate (7), falcarin­diol-8-acetate (8), alpha-mono palmitin (13), stigmasterol (1), and daucosterol (14) by the spectral evidences. These compounds were tested with COX-1 and COX-2 inhibition assays. This study found that compounds 2, 4, 5, 6, 7, 8, and 10 inhibited COX-1 dependent conversion of the exogenous arachidonic acid to $PGE_2$ in a dose-dependent manner with $IC_{50}$ values of $134.2{\mu}M$, $121.6{\mu}M$, $170{\mu}M$, $50.4{\mu}M$, $11.7{\mu}M$, $99.6{\mu}M$, and $69.6{\mu}M$, respectively. But, most of these compounds weakly inhibited COX-2 dependent $PGE_2$ generation. Among them, only compound 4 showed relatively significant inhibitory activity $(IC_{50}\;:\;127.6{\mu}M)$.

• Journal of Life Science
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• v.18 no.1
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• pp.96-102
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• 2008

Piceatannol is a polyphenol that is found in abundant quantities in grapes and wine. Although recent experimental data revealed the anti-cancer potency of piceatannol, the molecular mechanisms underlying the antileukemic activity have not yet been studied in detail. In the present study, we investigated further possible mechanisms by which piceatannol exerts its anti-proliferative action in cultured human leukemia U937 cells. Exposure of U937 cells to piceatannol resulted in growth inhibition and induction of apoptosis as measured by MTT assay and flow cytometry analysis, which was associated with S phase arrest of the cell cycle. Piceatannol treatment markedly inhibited the activity of telomerase, and the levels of human telomerase reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1), main determinants of the telomerase enzymatic activity, were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. However, the levels of cyclooxygenases (COXs) expression and prostaglandin E2 (PGE2) release were not changed in piceatannol-treated U937 cells. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of piceatannol.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.1019-1030
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• 2003

Platycodi Radix, the root of Platycodon grandiflorum, commonly known as Doraji, is used as a traditional oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the growth of human lung carcinoma A549 cells. Results obtained are as fellow; AEPG treatment resulted in the inhibition of the cell viability of A549 cells in a concentration-dependent manner. Upon treatment with AEPG, A549 cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that AEPG increased populations of apoptotic-sub G1 phase. Western blot and RT-PCR analyses indicated that the expressions of Bcl-2 was down-regulated but Bax was up-regulated in AEPG-treated A549 cells. AEPG-induced apoptotis of A549 cells was associated with rroteolytic cleavage and activation of caspase-3, release of cytochrome c from mitochondria into cytosol and down-regulation of Akt and phospho-Akt proteins in a dose-dependent manner. Induction of apoptosis by AEPG treatment was associated with inhibition and/or degradation of apoptotic target proteins such as poly(ADP-ribose) polymerase, β-catenin and phospholipase C-γ 1. AEPG treatment inhibited the levels of cyclooxygenases protein of A549 cells, which was associated with the inhibition of prostaglandin E2 accumulation in a concentration-dependent fashion. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.

• Natural Product Sciences
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• v.3 no.1
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• pp.19-28
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• 1997

Constitutive cyclooxygenase (COX-I) is present in cells under physiological conditions, whereas inducible cyclooxygenase (COX-II) is induced by some cytokines, mitogens, and endotoxin presumably in pathological conditions such as inflammation. We have evaluated the inhibitory effects of solvent fractionated extracts of natural products on the activities of COX-I and COX-II. Oxygen uptake COX assay was performed, as a primary screening from the tissue extracts of bovine seminal vesicles (BSV), by monitoring the initial rate of oxygen uptake using an oxygen electrode. Additionally, we evaluated plant extracts for the inhibitory effects of COX-I (in HEL cells) and COX-II (in lipopolysaccharide activated J774A.1 macrophages) using thin layer chromatography of prostanoids produced from $^{14}C-labelled$ arachidonic acid (AA). The use of such models of COX-I and COX-II assay will lead to the identification of specific inhibitors of cyclooxygenases with presumably less side effects than present therapies. Inhibitory effects of 50 kinds of plant extracts on the COX-I and COX-II activities were determined and the active fractions were found in the ethyl acetate fractions of Dryopteris crassirhizoma (roots), Amomum cardamomum (roots), Triticum aestivum (seeds), Perilla sikokiana (leaves), Anemarrhena asphodeloides (roots). Especially, the ethyl acetate fraction of Dryopteris crassirhizoma (roots), which exhibited the strong inhibition against BSV COX $(IC_{50},\;65.4\;{\mu}g/ml)$, COX-I $(IC_{50},\;8.5\;{\mu}g/ml)$, and COX-II $(IC_{50},\;17.2\;{\mu}g/ml)$, is under investigation to isolate active principles using activity-guided fractionation method.

• Journal of Life Science
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• v.14 no.3
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• pp.445-452
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• 2004

We investigated the cytotoxic effects of seven furanoterpenoids 〔sarcotin A, epi-sarcotin A, ircinin-1, epi-sarcotrine B, sarcotin I, (8E, l3Z, 20Z)-strobilinin/(7E,l3Z, 20Z)-felixinin and (7E,12E,18R,20Z)-variabilin〕 isolated from the sponge Sarcotragus sp. (the order Dictyoceratida) on the growth of A549 human lung carcinoma cells. MTT data revealed that sarcotin A and (7E,12E,18R,20Z)-variabilin exhibited higher potencies on the anti-proliferative activities than the other compounds in A549 cells. The growth inhibition by treatment with compounds (especially epi-sarcotin A, ircinin-1 and epi-sarcotrine B) were associated with the induction of apoptotic cell death through the concentration-dependent increase of Bax/Bcl-2 ratio in a p53-dependent or independent pathway Additionally, epi-sarcotin A and ircinin-1 strongly inhibited the levels of cyclooxygenase (COX)-2 expression without alteration of COX-1. Taken together, the results suggest that the furanoterpenoids from the marine sponge have strong potentials as candidates for anti-cancer drugs.

• Journal of Life Science
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• v.18 no.6
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• pp.884-890
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• 2008

Genistein, an isoflavone in soybean products, is a potential chemopreventive agent against various types of cancer. There are several studies documenting molecular alterations leading to cell cycle arrest at G2/M phase and induction of apoptosis; however, its mechanism of action and its molecular targets on the prostaglandin $E_2$ ($PGE_2$) production and telomere length regulation in human cancer remain unclear. In this study, we investigated the effect of genistein on the levels of cyclooxygenases (COXs) and telomere regulatory components of several human cancer cell lines (T24, human bladder carcinoma cells; U937, human leukemic cells; AGS, human stomach adenocarcinoma cells and SK-MEL-2, human skin melanoma cells). Genistein treatment resulted in the inhibition of cancer cell proliferation in a concentration-dependent manner. It was found that genistein treatment markedly decreased the levels of COX-2 mRNA and protein expression without significant changes in the expression of COX-1, which was correlated with a decrease in $PGE_2$ synthesis. Genistein treatment also partly inhibited the levels of human telomerase reverse transcriptase (hTERT) as well as human telomerase RNA (hTR) and telomerase-associated protein (TEP)-1, and the activity of telomerase. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of genistein.

• Journal of Life Science
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• v.19 no.4
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• pp.502-507
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• 2009

In modern oriental medicine, bee venom therapy is being used for aqua-acupuncture to relieve pain and to cure inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and gout. Bee venom therapy has been processed and reported in many experimental studies, with regard to its effects on pain alleviation, anti-inflammation, removal of fever, anti-convulsion, suppression of tumor and immunity strengthening, etc., however, its mechanism of action, molecular targeting on prostaglandin $E_2$ ($PGE_2$) production and telomere length regulation in human cancer remains unclear. In this study, we investigated the effect of bee venom on the levels of cyclooxygenases (COXs) and telomere regulatory components of A549 human lung cancer cells. Bee venom-induced anti-proliferative effects of A549 cells were associated with the inhibition of human telomerase reverse transcriptase (hTERT) as well as human telomerase RNA (hTR), transcription factor c-myc and the activity of telomerase. In addition, bee venom treatment markedly decreased the levels of COX-2 mRNA and protein expression without significant changes in the expression of COX-1, which was correlated with a decrease in $PGE_2$ synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of bee venom.