• Journal of Life Science
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• v.19 no.8
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• pp.1009-1015
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• 2009

The beneficial use of sedatives is often required for medically ill patients. This study examined the effect of plant flavonoids and diazepam peripheral-type benzodiazepine receptor (PBR) activation and glucose utilization in breast cancer cells, along with their interactions. In estrogen receptor negative MDA-MB-231 cells, the anti-proliferative activity of fisetin (3,7,3',4'-tetrahydroxyflavone) and diazepam was more prominent than in estrogen receptor positive MCF-7 cells. Unlike PBR ligands, treatment with $10^{-6}$ M concentration of diazepam for 3 days exhibited anti-proliferative effects, while similar to apigenin (4',5,7-Trihydroxyflavone) and fisetin, diazepam hardly affected the PBR mRNA expression by MDA-MB-231 cells. Treatment with $10^{-6}$ M concentration of flavonoids and diazepam for 3 days inhibited the glucose utilization of MDA-MB-231 cells. Treatment with $10^{-6}$ M concentration of flavonoids and diazepam for 6 days showed increased cytotoxicity and reduced the PBR mRNA expression of the MDA-MB-231 cells. Apigenin enhanced diazepam-induced anti-proliferative effects on the MDA-MB-231 cells as well. All together, this study showed the in vitro anti-proliferative activity of flavonoids and diazepam on MDA-MB-231 breast cancer cells, plus additive enhancements. In conclusion, this study provides experimental basis for advanced trials in the future.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.309-314
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• 2006

The multicellular layers(MCL) of human cancer cells is a three dimensional(3D) in vitro model for human solid tumors which has been used primarily for the assessment of avascular penetration of anti-cancer drugs. For anti-cancer drugs with penetration problem, MCL represents a good experimental model that can provide clinically relevant data. Calcein-AM is a fluorescent dye that demonstrates the cellular vitality in a graded manner in cancer cell culture system. In the present study, we evaluated the use of calcein-AM for determination of anti-proliferative activity of anti-cancer agents in MCL model of DLD-1 human colorectal cancer cells. Optical sectioning of confocal imaging was compromised with photonic attenuation and penetration barrier in the deep layers of MCL. By contrast, fluorescent measurement on the cryo-sections provided a feasible alternative. Cold pre-incubation did not enhance the calcein-AM distribution to a significant degree in MCL of DLD-1 cells. However, the simultaneous determination of drug penetration and cellular vitality appeared to be possible in drug treated MCL. In conclusion, these data suggest that calcein-AM can be used for the simultaneous determination of drug-induced anti-proliferative effect and drug penetration in MCL model.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.21-31
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• 2006

In the present study, We have investigated the bee venom (BV) and melittin (a major component of BV)-mediated anti-proliferative effects, and defined its mechanisms of action in cultured rat aortic vascular smooth muscle cells (VSMCs). BV and melittin $(0.4{\sim}0.8\;{\mu}g/ml)$ effectively inhibited 5% FBS-induced VSMCs proliferations. The regulation of apoptosis has attracted much attention as a possible means of eliminating excessively proliferating VSMCs. In the present study, the treatment of BV and melittin strongly induced apoptosis of VSMCs. These results suggest that the anti-proliferative effects of BV and melittin in VSMCs should be related with induction of apoptosis. Further study about Influence of BV and melittin upon apoptosis mechanism is therefor thought to be necessary to confirm the above results.

• Journal of Medicine and Life Science
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• v.15 no.1
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• pp.6-11
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• 2018

Previous studies have suggested that Citrus fruits might suppress the proliferation of various cancer cells. However, little is known about any specific ingredients in the extract of Citrus fruits to exert its anti-proliferative activity in cancer cells. The present study aimed to identify the active ingredients in Citrus fruits to suppress the proliferation of rat hepatocellular carcinoma cells. Among tested compounds, two polymethoxylated flavones (nobiletin and tangeritin) showed significant anti-proliferative activity whereas other compounds (synephrine, rutin, hesperidin) did not. Interestingly, nobiletin as well as tangeritin also decreased the protein amount of gluconeogenic enzymes, PEPCK and G6Pase. The possible involvement of gluconeogenic activity in the proliferation of hepatocellulacarcinoma cells are further to be investigated.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5325-5329
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• 2015

Farnesiferol C is a natural compound with various anti-cancer properties that belongs to the class of sesquiterpene coumarins. However, the low bioavailability of farnesiferol C limits its therapeutic potential. Here, we overcame this problem utilizing dendrosome nano-particles and evaluated the anti-cancer effect of dendrosomal farnesiferol C (DFC) on the AGS gastric cancer cell line. The 3-(4,5-dimethyl-thiazol-2yl)-2,5- diphenyl tetrazolium bromide (MTT) assay and reverse transcriptase-polymerase chain reaction (RT-PCR) were respectively used to detect the anti-proliferative properties of DFC and expression ratio of Bax/Bcl-2 as a hallmark of apoptosis. Compared to the void farnesiferol C (FC), our data showed that DFC significantly suppresses the proliferation of AGS cells in a time- and dose-dependent manner (P<0.01). Also, DFC meaningfully increased the expression ratio of Bax/Bcl-2 in AGS cells (P<0.01). The findings demonstrate that our nano-based formulation of farnesiferol C could be considered as a potential therapeutic agent in cancer targeting.

• The Journal of Internal Korean Medicine
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• v.28 no.3
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• pp.608-614
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• 2007

Objectives : This study was carried out to investigate anti-proliferative effects on MCF-7 human breast cancer cells of Anemarrhenae Rhizoma (AR) extract. Breast cancer is the most common disease in Korean women. Despite remarkable improvements in treatment strategies against various cancers during the past 40 years. breast cancer still remains as one of the main causes of cancer mortality among women the whole world over. Methods : Be investigated the effects of AR on cytotoxicity of MCF-7 human breast cancer cells in various extract conditions (n-hexane, ethyl acetate, butanol and water fraction). Results : The extract of Anemarrhenae Rhjzoma inhibits the proliferation of MCF-7 cells in a dose dependent manner. Especially. the ethyl acetate fraction of Anemarrhenae Rhizoma showed specific Cytotoxicity on MCF-7 cells. Conclusions : In conclusion. it can be concluded that Anemarrhenae Rhizoma extract has an anti-proliferative effect on MCF-7 human breast cancer cells. Especially. the ethyl acetate fraction is most effective to inhibit proliferation of MCF-7 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5317-5323
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• 2013

Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of $r^2$=0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an $IC_{50}$ value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.

• Journal of Life Science
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• v.25 no.7
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• pp.773-779
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• 2015

This study examined extracts from five different kinds of lees and nuruk and their organic solvent fractions in terms of several biological functions, such as anti-adipogenic, anti-inflammatory, and anti-proliferative activities. The anti-adipogenic activity was investigated by treating mouse pre-adipocyte 3T3-L1 cells with one extract (YE) and four organic solvent fractions (YAc, PAc, RAc, and WPAc) during adipogenesis. Among the treated samples, the ethyl acetate fraction of W-Ju lees (WPAc) showed the strongest anti-adipogenic effect, which was confirmed with oil red O staining and down-regulation of pro-adipogenic genes such as PPAR-gamma and SCD-1. Treatment with WPAc also reduced the expression of PPAR-gamma in a time-dependent manner. The effects of five different extracts were examined on nitric oxide (NO) production in mouse RAW 264.7 cells to determine anti-inflammatory activity. The ethyl acetate fraction of B-Ju lees (PAc) significantly decreased NO production in LPS-stimulated RAW 264.7 cells and it also inhibited NO production in a dose-dependent manner. The PAc fraction also dramatically decreased the viability of human colorectal cancer HCT116 cells in a dose-dependent manner. In addition, PAc increased the expression of NAG-1 and ATF3 genes in a dose dependent manner. Overall, these results indicate that lees and nuruk have several biological functions, including anti-adipogenic, anti-inflammatory, and anti-proliferative activities.

• International Journal of Oral Biology
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• v.30 no.4
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• pp.111-116
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• 2005

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a naturally occuring polyphenol compound which present in the skin of grapes and red wine has been considered to posses chemopreventive and antioxidant properties. However, little is known about the cellular actions by which resveratrol mediates its therapeutic effects. In this study, the effect of resveratrol on cell proliferation and induction of apoptosis in human osteogenic sarcoma (HOS) cells was investigated. $IC_{50}$ value was determined to be approximately $6.0{\mu}g/ml$. Chromosomal DNA framgmentation analysis showed the appearance degraded DNA in time-and dose-dependent manner upon treatment of resveratrol. In order to observe the molecular mechanism involved in resveratrol-induced apoptosis, Western blot analysis was performed. We observed the decrease in the level of procaspase-3, the zymogen form of active caspase-3 in resveratrol-treated cells. This result implies that caspase-3 is activated upon treatment of resveratrol. The activation of caspase-3 was confirmed by the cleavage of poly(ADP-ribose) polymerase. Taken together, our data demonstrate that resveratrol has anti-proliferative effect on HOS cells and induced apoptosis through activation of caspase-3 and PARP cleavage.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.616-624
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• 2022

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC₅₀ of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC₅₀ of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.