• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.12
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• pp.1679-1684
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• 2009

Opuntia humifusa, widely distributed in the southern regions of the Korean peninsula, is known to have bioactive functions and medicinal benefits for treating various diseases such as arteriosclerosis, diabetes mellitus, gastritis, and hyperglycemia. In this study total polyphenol and flavonoid contents of fruit and its anticarcinogenic effects on human breast cancer were investigated. As expected, O. humifusa showed high concentrations of total polyphenol as well as flavonoid as compared to other kinds of cactus. Effects of the water extracts of O. humifusa on the proliferation, G1 arrest and apoptosis of the MCF-7 human breast cancer cells were also examined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, and G1 cycle arrest and apoptotic effect of O. humifusa were analyzed by flow cytometry. When MCF-7 cells were treated with different concentrations of hexane, ethyl acetate and water extracts of O. humifusa, water extracts of the fruit significantly decreased viable cell numbers in a concentration dependent manner. A G1 arrest in MCF-7 cells was induced as well. The overall results indicate that water extracts of fruit of O. humifusa would inhibit MCF-7 human breast cancer cell proliferation and induce G1 arrest.

• Journal of Life Science
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• v.15 no.2 s.69
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• pp.169-175
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• 2005

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. $Amyloid-\beta$ deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease. In this study, we have explored the effects of resveratrol on $amyloid-\beta-peptide-mediated$ cytotoxicity in vitro and modulation of cell growth-regulatory gene products in astroglioma C6 cells to elucidate its possible mechanism for anti-cytotoxicity. Exposure of C6 cells to $Amyloid-\beta$ resulted in dose-dependent growth inhibition and morphological changes of C6 cells, which were recovered by pre-treatment with resveratrol. The anti-proliferative effect of $amyloid-\beta$ was associated with the induction of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) expression assessed by RT-PCR and Western blot analysis in time-dependent manner in C6 cells. In addition, the pro-apoptotic Bax expression was also up-regulated in $amyloid-\beta-treated$ C6 cells without alteration of anti-apoptotic Bcl-2 and $Bcl-X_L$ expression. However, pre-treatment of resveratrol significantly inhibited $amyloid-\beta-induced$ p53, p21 and Bax levels, suggesting that the modulation of p53, p21 and Bax levels could be one of the possible pathways by which resveratrol functions as anti-cytotoxic agent. Our results demonstrate that resveratrol may enhance the protection against $amyloid-\beta-induced$ cytotoxicity by promoting the survival of glial cells.

• Journal of Life Science
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• v.29 no.10
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• pp.1062-1070
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• 2019

A components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. We aimed to investigate the capacity of garlic compounds to anti-tumor on a various cancer cell lines. Fractionation of garlic extract, guided by antiproliferative activity against human gastric cancer (AGS) cells, has resulted in the isolation of N-benzyl-N-methyldecan-1-amine (NBNMA). We investigated the effect of newly isolated NBNMA from garlic cloves on the inhibition of the growth of CT-26, AGS, HepG2, HCT-116, MCF7, B16F10, and Sarcoma-180 cells for in vitro and CT-26 colon carcinoma cells in vivo. NBNMA exhibited an antiproliferative effect in CT-26 cells by apoptotic cell death. NBNMA exhibited down-regulation of anti-apoptotic Bcl-2 proteins and up-regulation of apoptotic Bad protein expression in western blot analyses. In addition, NBNMA meagre activated caspase 3 and caspase 9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis. NBNMA treatment at a dose of 10 mg/kg for 21 days in experimental mice implanted with tumors resulted in significant reduction of the tumor weight (43%). NBNMA exhibited both in vitro and in vivo anticancer activity. These results indicate that NBNMA has promising potential to become a novel anticancer agent from garlic cloves for the treatment of colon carcinoma cancer.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.2
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• pp.69-78
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• 2017

Cordyceps militaris has been used in traditional Chinese medicine owing to its anticancer and immunomodulatory activities. Germanium compounds have also been shown to be associated with many pharmacological functions, such as antimicrobial, antiviral, antitumor, antimutagenic, and immunomodulating effects. In this study, we examined the biological properties of hot water extract from mycelial liquid culture of germanium-enriched C. militaris (CMGe). CMGe displayed a concentration-dependent antiproliferation activity against four human cancer cell lines. The antiproliferative activity of CMGe was 2-4-fold lower than that of hot water extract from mycelial liquid culture in C. militaris (CM). However, CM had a concentration-dependent cytotoxicity to human bone marrow-derived mesenchymal stem cells (MSCs). Contrastingly, CMGe did not cause any cellular damage to MSCs. MSCs cultured with CMGe displayed an increased proliferative activity with no cytotoxic effect. The oral administration of CMGe inhibited increased tumor volume and weight compared with the control group. CMGe has the potential to be used as an industrial product in medicinal foods as well as in pharmaceutical products.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7179-7186
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• 2013

Background and Aims: Scutellaria is one of the most popular traditional Chinese herbal remedies against various human diseases, including cancer. In this study, we examined the active effects of Scutellaria extract and its main flavonoid constituents on the proportion of side population cells within human multiple myeloma cell line RPMI8226 in vitro and explored the potential molecular mechanisms involved. Materials and Methods: The contents of flavonoids in ethanolic extract of Scutellaria baicalensis Georgi were determined using high performance liquid chromatography. The antiproliferative effect of the ethanolic extract on RPMI-8226 was determined by CCK assay. Apoptosis was measured by annexin combining with propidium iodide in a flow cytometer. Cell cycle analysis was performed by propidium iodide staining in combination with flow cytometry analysis. Hoechst 33342 exclusion assay was used for the identification of side population within RPMI8226 cells. The expression of ABCG2 protein was assessed by Western blotting assay. Results: The content of major flavonoids constitutents of Scutellaria extract was baicalin (10.2%), wogonoside (2.50%), baicalein (2.29%), and wogonin (0.99%), respectively. The crude Scutellaria extract did not show significant anti-proliferative effect, apoptosis induction and cell cycle arrest in RPMI-8226 within the concentrations of $1-75{\mu}g/mL$. However, the ethanolic extract, baicalein, wogonin and baicalin reduced the side population cells in RPMI-8226, and data showed that baicalein and wogonin had stronger inhibitory effects. Correspondingly, they also exhibited significant effects on decreasing the expression level of ABCG2 protein in RPMI-8226 in vitro. Conclusions: Our results for the first time demonstrated a novel mechanism of action for Scutellaria extract and its main active flavonoids, namely targeting SP cells by modulating the expression of ABCG2 protein. This study provides an insight for new therapeutic strategies targeting cancer stem cells of multiple myeloma.

• Journal of Gastric Cancer
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• v.13 no.3
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• pp.172-178
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• 2013

Purpose: The aims of this study were as follow: 1) to de scribe the expression status of estrogen receptor-${\alpha}$ and -${\beta}$ mRNAs in five gastric carcinoma cell lines; 2) to evaluate in vitro the effects of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of the cell lines. Materials and Methods: Detection of estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNA in five human gastric cancer cell lines (AGS, KATO III, MKN28, MKN45 and MKN74) was made by the reverse transcription-polymerase chain reaction system. To evaluate the effect of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of gastric cancer cell line, the cell lines which expressed both es trogen receptors were chosen and treated with $17{\beta}$-estradiol and estrogen receptor antagonists (methyl-piperidino-pyrazole and pyrazolo [1,5-a] pyrimidine). Cell proliferation was assessed with the methylthiazol tetrazolium test. Results: Estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNAs were expressed in three (KATO III, MKN28 and MKN45) and all of the five gastric cancer cell lines, respectively. At higher concentrations, $17{\beta}$-estradiol inhibited cell growth of MKN28, MKN45 and KATO III cell lines. Neither estrogen receptor-${\alpha}$ nor estrogen receptor-${\beta}$ antagonist blocked the anti-proliferative effect of $17{\beta}$-estradiol. Conclusions: Our results indicate that estrogen receptor-${\beta}$ mRNAs are preferentially expressed in gastric cancers and also imply that hormone therapy rather than estrogen receptor blockers may be a useful strategy for the treatment of estrogen receptor-${\beta}$ positive gastric cancer. Its therapeutic significance in gastric cancer are, however, limited until more evidence of the roles of estrogen receptors in the gastric cancer are accumulated.

• Molecules and Cells
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• v.37 no.7
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• pp.547-553
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• 2014

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

• Toxicological Research
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• v.24 no.1
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• pp.29-36
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• 2008

The present study investigated the anti-proliferative and chemosensitizing effects of Crinum asiaticum var. japonicum against multi-drug resistant (MDR) cancer cells. The 80% methanol extract, chloroform ($CHCl_3$) fraction and butanol (BuOH) fraction of C. asiaticum inhibited the growth of mitoxantrone (MX) resistant HL-60 (HL-60/MX2) cells. When HL-60/MX2 cells were treated with the $CHCl_3$ and BuOH fractions, DNA ladder and sub-G1 hypodiploid cells were observed. Furthermore, the fractions reduced BcI-2 mRNA levels, whereas Bax mRNA levels were increased. These results suggest that the inhibitory effect of C. asiaticum on the growth of the HL-60/MX2 cells might arise from the induction of apoptosis. Treatment of HL-60/MX2 cells with the fractions markedly decreased the mRNA levels of the multi-drug resistance protein-1 and breast cancer resistance protein. The $CHCl_3$ fraction and hexane fraction increased MX accumulation in HL-60/MX2 cells. These results imply that the $CHCl_3$ fraction of C. asiaticum plays a pivotal role as a chemosensitizer. We suggest that components of C. asiaticum might have a therapeutic potential for the treatment of MDR leukemia.

• Biomolecules & Therapeutics
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• v.13 no.2
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• pp.78-83
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• 2005

2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) has previously shown to induce neurotoxicity through intracellular $Ca^{2+}$ increase in rat neurons. In this study we investigated the role and signaling pathway of intracellular $Ca^{2+}$ in TCDD-induced inhibition of neuronal cell proliferation in SK-N-SH human neuronal cells. We found that TCDD(10nM) rapidly increased the level of intracellular $Ca^{2+}$, which was completely blocked by the extracellular $Ca^{2+}$ chelation with EGTA (1 mM) or by pretreatment of the cells with the non-selective cation channel blocker. flufenamic acid (200 ${\mu}M$). However, pretreatment of the cells with dantrolene (25 ${\mu}M$) and TMB-8(10 ${\mu}M$), intracellular $Ca^{2+}$-release blockers, or a voltage-sensitive $Ca^{2+}$ channel blocker, varapamil (100 ${\mu}M$), failed to block the TCDD-induced $Ca^{2+}$ increase in the cells. In addition, TCDD induced a rapid and transient activation of phatidvlinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2(ERK1/2), which was ingnificantly blocked by the pretreatment with BAPTA, an intracellular $Ca^{2+}$ chelator, and LY294002, a PI3K inhibitor. Furthermore, inhibitors of PI3K, ERK, or an intracellular $Ca^{2+}$ chelator further potentiated the anti-proliferative effect of TCDD in the cells. Collectively, the results suggest that intracellular $Ca^{2+}$ and PI3K-dependent activation of ERK 1/2 may be involved in the TCDD-induced inhibition of cell proliferation in SK-N-SH human neuronal cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.1
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• pp.137-142
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• 2016

We investigated the anti-proliferative effects of solar salt and purified salt (PS) on HepG2 human hepatocellular cancer cells as well as their effects on mRNA and protein expression of apoptosis- and cell cycle-related genes, including Bcl-2, Bax, p53, and p21. Each salt sample suppressed cancer cell proliferation when treated at a concentration of 0.5% or 1%. Especially solar salt from T salt field (SS-T) and solar salt from Y salt field (SS-Y) significantly suppressed proliferation of cancer cells in comparison with PS. Treatment of HepG2 cells with salt samples at a concentration of 1% suppressed expression of Bcl-2 and promoted expression of Bax, p53, and p21 at the mRNA and protein levels in comparison with the control group. Inductively coupled plasma optical emission spectrometry (ICP-OES) showed that SS-T and SS-Y had higher concentrations of Ca, Mg, S, and K than PS, and SS-T contained higher concentrations of these minerals than SS-Y. It seems that Na and mineral contents in solar salt may contribute to regulation of the genes. Taken together, salt, especially mineral rich solar salt, inhibits cancer cell growth by regulating apoptosis and cell cycle-related genes.