• Journal of Life Science
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• v.24 no.1
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• pp.8-13
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• 2014

The moringa (Moringa oleifera Lam.) plant is used as food and as an anti-allergic agent. In this study, we studied the inhibitory effect of moringa root extract on the expression of PMA-induced matrix metalloproteinase-9 (MMP-9), which is the main factor implicated in the invasion and metastasis of cancer cells in MCF-7 cells. At first, various moringa extracts were examined in the MCF-7 cells. Both moringa root extract and leaf extracts inhibited PMA-induced MMP-9 activity, but the root extract suppressed PMA-induced MMP-9 activity to a greater extent than the leaf extract. The moringa root extract also inhibited PMA-induced MMP-9 protein expression and cell invasion. According to RT-PCR, the treatment of the MCF-7 cells with moringa root extract decreased levels of PMA-induced MMP-9 mRNA expression, but not the expression of TIMP-1 and -2, indicating that moringa root extract prevents the transcription of MMP-9 in response to PMA. In addition, moringa root extract specifically suppressed the phosphorylation of ERK/JNK, but not p38. We suggest that moringa root extract abolishes MMP-9 activity/expression through ERK/JNK. In conclusion, moringa root extract suppressed PMA-induced MMP-9 activity/expression by inhibiting the phosphorylation of ERK/JNK in MCF-7 cells. These results indicate that moringa root extract may be a potential antimetastatic and anti-invasive agent. Future clinical research is needed on the anticancer properties of moringa root extract.

• Journal of Life Science
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• v.19 no.11
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• pp.1581-1590
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• 2009

Hizikia fusiforme is a kind of brown edible seaweed that mainly grows in the temperate seaside areas of the northwest pacific, including Korea, Japan and China, and has been widely used as a health food for hundreds of years. Recently, H. fusiforme has been known to exert pharmacological activities including antioxidant, antimutagenic and anticoagulant activities. However, the molecular mechanisms of H. fusiforme in malignant cells have not been clearly elucidated yet. In this study, the effects of ethyl alcohol extract of H. fusiforme (EAHF) on the anti-proliferative effects of MDA-MB-231 and MCF-7 human breast cancer cells were investigated. EAHF treatment resulted in a concentration-dependent growth inhibition by including apoptosis in MDA-MB-231 cells and G1 phase arrest in MCF-7 cells, which could be proved by MTT assay, DAPI staining, agarose gel electrophoresis and flow cytometry analysis. In MDA-MB-231 cells, the increase in apoptosis induced by EAHF treatment correlated with up-regulation of pro-apoptotic Bax expression. EAHF treatment induced the proteolytic activation of caspase-3 and caspase-9, and a concomitant inhibition of poly (ADP-ribose) polymerase, $\beta$-catenin, phospholipase-${\gamma}1$ protein and DNA fragmentation factor 45/inhibitor of caspase-activated DNase. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. fusiforme.

• The Korea Journal of Herbology
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• v.21 no.1
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• pp.57-62
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• 2006

Objectives : This study was carried out to investigate the inhibitive effects of cotton plant sectional extracts in cancer cell lines, Calu-6(human, Caucasian, lung, adenocarcinoma) and MCF-7(human, Caucasian, breast, adenocarcinoma). The incidence of cancer has been increasing even in korea due to the change of dietary life and westernization and becoming conspicuous as the disease threatening health. But cancer treatment have not been fully effective against the high incidence or low survival rate of most cancer. Methods : Calu-6 and MCF-7 cells were cultured and seeded in cell culture plates, respectively. And sectional extracts of cotton plant were treated to MCF-7 cells. Results and Conclusion : Sectional extracts of cotton plant showed no anti-proliferative effect on MCF-7 cells, but root and stem extracts showed strong anti-proliferative effects on Calu-6 cells. Fruit, leaf and flower extracts also showed anti-proliferative effects on Calu-6 cells but not so much like root and stem extracts. But seed extract showed no anti-proliferative effect on Calu-6 cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.5
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• pp.613-618
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• 2005

This study was carried out to examine the effects of gamma irradiation on the cytotoxicity and multidrug-resistance reversing activity of methanol extracts from Coix lachryma-jobi L. var. me-yuen Stapf seed. The seed was irradiated with doses of 1, 4, 8, 16, 32 and 64 Gy of the gamma radiation, and then extracted by methanol. The extracts were examined for cytotoxicity on the human cancer cell lines, MCF-7 (human breast adenocarcinoma pleural effusion), Calu-6 (human pulmonary carcinoma) and SNU-601 (human gastric carcinoma) cells, and investigated for multidrug-resistance reversing activity using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. The growth inhibitory activity of irradiated seed extracts on human cancer cell lines was higher than that of the control. In the case of Calu-6 cell line, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. $IC_{50}$ value in the MCF-7 cell line was measured in the only 8 Gy extract. And in the SNU-601 cell line as Calu-6, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. But the extracts of gamma-irradiated seed over 32 Gy showed little growth inhibitory effect against human cancer cell lines. In this result, 8 Gy extract had significant growth inhibitory in all human cancer cell lines $(Calu-6:\;633\;{\mu}g/mL,\;MCF-7:\;653\;{\mu}g/mL\;and\;SNU-601:\;683\;{\mu}g/mL)$. The extracts of 4, 8 and 16 Gy strongly potentiated vincristine cytotoxicity in AML-2/D100 cells. The reversal fold (RF) of 4, 8 and 16 Gy extracts was 1.7, 1.8 and 1.6, respectively. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. These results indicate that the above samples would contain some principles which have cytotoxicity and multidrug-resistance reversing activity. Irradiation technology can be applied to promote physiological activities of medicinal plant seeds.

• Journal of Life Science
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• v.19 no.9
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• pp.1251-1257
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• 2009

We investigated the growth inhibitory effect of internal organs of Todarodes pacificus (TP) on proliferation in human cancer cell lines in vitro. The internal organs of TP were extracted with methanol (TPM), which was then further fractionated into four subfractions by using a solvent partition method, resulting in hexane (TPMH), methanol (TPMM), butanol (TPMB), and aqueous (TPMA) soluble fractions. We determined the cytotoxic effect of these four fractions in three kinds of cancer cell lines - HepG2, MCF-7 and HT-29 - by MTT assay. Among the four subfractions of TPM, TPMH showed the strongest cytotoxic effects at a concentration of $300{\mu}g$/ml, displaying 91.56% on the HepG2 cell line and 85.93% on the MCF-7 cell line. Morphological changes such as membrane shirinking and blebbing of cells were also observed during TPMH treatment of HepG2 cells. In addition, we also observed quinone reductase (QR) induced effect in the methanol (TPMM) layer of HepG2 cells. TPMM showed the highest induction activity of quinone reductase on HepG2 cells among the other partition layers. The QR induced effect of TPMM was determined to be 2.7 at a level of $360{\mu}g$/ml with a control value of 1.0. Although further studies are needed, the present work suggests that internal organs of Todarodes pacificus (TP) may be a chemopreventive agent for the treatment of human cells.

• The Journal of Korean Obstetrics and Gynecology
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• v.20 no.1
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• pp.32-49
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• 2007

Purpose: Breast cancer is the most common disease in Korean women. Despite remarkable improvements in treatment strategies against various cancer during the past 40 years, breast cancer still remains as one of the main causes of cancer mortality among women in the whole world. This study was carried out to investigate antioxidative and anti-proliferative effects on MCF-7 human breast cancer cells of Ikiyangyoung-Tang extract. Methods: We measured a content of polyphenol and flavonoid in the Ikiyangyoung-Tang extract, eliminative ability of DPPH radical, ABTS free radical and hydrogen peroxide, antioxidative effects of linoleic acid, cytotoxicity on MCF-7 human breast cancer cells. MCF-7 cells were cultured in Dulbecco's modified Eagle's medium/F12(DMEM/F12) supplemented with 10 % fetal bovine serum(FBS; Gibco) and antibiotics. Results : The extract of Ikiyangyoung-Tang contains polyphenol of 168.3${\pm}$12.8 ${\mu}$g/mg and flavonoid of 84.3${\pm}$3.4 ${\mu}$g/mg. Above results show profitable abilities of elimination of ${\alpha}$-${\alpha}$-Diphenyl-${\beta}$-picrylhydrazyl(DPPH) radical, ABTS free radical and hydrogen peroxide. Also, the extract of Ikiyangyoung-Tang strongly inhibits the proliferation of MCF-7 cells in a dose ependent manner. And. it has cytotoxicity on NIH3T3 cells. Conclusion : It can be concluded that Ikiyangyoung-Tang extract has an antioxidative effect and antiproliferative effect on MCF-7 human breast cancer cells.

• Journal of Life Science
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• v.8 no.6
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• pp.638-647
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• 1998

Protein Kinase C (PKC) activators, phorbol 12-myristate 13-acetate (PMA), bryostatin, and dioctanoyl glycerol (DiC8), induce translocation of PKC isozymes from cytoplasm to plasma membrane or into nucleus. The activated PKC negatively modulates growth of human breast cancer cells. Antiproliferative effect and translocation of PKC were investigated in MCF-7 cells. The translocation of activated PKC isozymes by PMA, bryostatin and DiC8 was occurred at the various different regions in MCF-7 cell. PKC $\alpha$ and $\beta$ could be translocated to the nucleus or the nuclear mem-brane, and PKC $\delta$and $\varepsilon$ to cell membrane by PMA while DiC8 and bryostatin induced the translocation of PKC $\alpha$ and $\beta$ to the nucleus or plasma membrane, respectively. In the antiproliferative effect of PKC activators, PMA ($IC_{50}$/ values of 1.2$\pm$0.3nM) and DiC8 ($IC_{50}$/ values of 5.0$\pm$1.1$\mu$M) inhibited the cell growth. Bryostatin also inhibited the cell growth but to a much less degree than one obser-ved with PMA : 16% growth reduction by 100nM bryostatin. However, PMA treated with bryostatin induced gro-wth inhibition, but PMA with DiC8 at 10$\mu$M was not effective. These results suggest that each PKC isozyme is tran-slocated to various specific sites, and that especially, PKC $\alpha$ isozyme plays an important role in control of antiprolife-raive function of cell growth.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.85-98
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• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.3
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• pp.487-493
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• 2004

This study has been undertaken to increase availability of native camellia in Jeonnam as a medicinal resource and to isolate the effective components from them. Fresh leaf and flower of camellia, single camellia tea and camellia tea mixed with green tea, herbs were screened for cytotoxicity on MCF -7 (human breast adenocarcinoma pleual effusion), Calu-6 (human pulmonary carcinoma), SNU-601 (human gastric carcinoma) cells. Also their multidrug-resistance reversing activity were evaluated using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. Among the camellia extracts, young leaf and camellia tea mixed with green tea had strong growth inhibitory effects in below 100 $\mu\textrm{g}$/mL against human cancer cells. In result, young leaf showed the strongest inhibitory effects on MCF -7 ($IC_{50}$/ = 100 $\mu\textrm{g}$/mL ↑), Calu-6 ($IC_{50}$/ = 79 $\mu\textrm{g}$/mL), and SNU -601 ($IC_{50}$/ = 39 $\mu\textrm{g}$/mL), and AML-2/WT ($IC_{50}$/ = 64 $\mu\textrm{g}$/mL). Chemosensitizing effect was the extracts of mature leaf ($IC_{50}$/ = 97 $\mu\textrm{g}$/mL, RF=3.0), roasted tea ($IC_{50}$/ = 76 $\mu\textrm{g}$/mL, RF = 2.6 ↑) and steam tea ($IC_{50}$/ = 70 $\mu\textrm{g}$/mL, RF=2.8 ↑) strongly potentiate vincristine cytotoxicity in AML-2/D100 cells. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. This results indicate that crude extracts of camellia mature leaves would contain some principles which have chemosensitizing activity.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.1
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• pp.37-44
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• 2023

Enterotoxigenic Bacteroides fragilis (ETBF) has been reported to promote colitis and colon cancer through the secretion of B. fragilis toxin (BFT), a zinc-dependent metalloprotease. In colonic epithelial cells, BFT induces the cleavage of E-cadherin into the 80 kDa ectodomain and the 33 kDa membrane-bound intracellular domain. The resulting membrane-tethered fragment is then cleaved by γ-secretase forming the 28 kDa E-cadherin intracellular fragment. The 28 kDa cytoplasmic fragment is then degraded by an unknown mechanism. In this study, we found that the 28 kDa E-cadherin intracellular fragment was degraded by the proteasome complex. In addition, we found that this sequential E-cadherin cleavage mechanism is found not only in colonic epithelial cells but also in the human breast cancer cell line, BT-474. Finally, we report that staurosporine also induces E-cadherin cleavage in the human breast cancer cell line, MCF7, through γ-secretase. However, further degradation of the 28 kDa E-cadherin intracellular domain is not dependent on the proteasome complex. These results suggest that the BFT-induced E-cadherin cleavage mechanism is conserved in both colonic and breast cancer cells. This observation indicates that ETBF may also play a role in the carcinogenesis of tissues other than the colon.