• Title/Summary/Keyword: Dose analysis

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Enhancement of Tumor Response by MEK Inhibitor in Murine HCa-I Tumors (C3H/HeJ 마우스 간암에서 MEK 억제제에 의한 방사선 감수성 향상 효과)

  • Kim, Sung-Hee;Seong, Jin-Sil
    • Radiation Oncology Journal
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    • v.21 no.3
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    • pp.207-215
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    • 2003
  • Purpose: Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protin kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Materials and Methods: Murine hepatocarcinoma, HCa-I is known to be highly radioresistant with a TCD50 (radiation dose yield in $50\%$ cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case on radioresistant tumor. C3H/HeJ mice hearing $7.5\~8\;mm$ HCa-I, were treated with PD98059(intratumoral injection of $0.16\;\mug/50\;\mul$). Results: Downregulation on ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to Increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number on apoptotic nuclei in 1000 nuclei X100) was $1.2\%$ in the case of radiation treatment alone, $0.9\%$ in the case of drug treatment alone and $4.9\%,\;5.3\%$ in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed upregulation of p53, p$p21^{WAF1/CIP1}\;and\;Bcl-X_s$ in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as $Bcl-X_L4, Bax and Bcl-2 were changed to a lesser extent. Conclusion: The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment.

Inhibitory Effects of Angiotensin Converting Enzyme and α-Glucosidase, and Alcohol Metabolizing Activity of Fermented Omija (Schizandra chinensis Baillon) Beverage (오미자 발효음료의 알코올 분해능과 Angiotensin Converting Enzyme 및 α-Glucosidase 저해효과)

  • Cho, Eun-Kyung;Cho, Hea-Eun;Choi, Young-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.5
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    • pp.655-661
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    • 2010
  • The nutraceutical role of fermented omija (Schizandra chinensis) beverage (FOB) was determined through the analysis of fibrinolytic and alcohol metabolizing activities, nitrite scavenging activity, and angiotensin converting enzyme and $\alpha$-glucosidase inhibitory effects. Firstly, FOB increased fibrinolytic activity in a dose-dependent manner and indicated angiotensin converting enzyme inhibitory activity of 94.8% at 20% FOB (0.6 mg/mL). In addition, the inhibitory activities of FOB on $\alpha$-amylase and $\alpha$-glucosidase were determined to be 100% at 100% FOB (3 mg/mL) and 49% at 60% FOB (1.8 mg/mL), respectively. Nitrite scavenging activity of FOB was about 96.1%, 72.3%, and 68.3% on pH 1.2, 3.0, and 6.0 at 100% FOB, respectively. To determine influence of FOB on alcohol metabolism, the generating activities of reduced-nicotinamide adenine dinucleotide (NADH) by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were measured. Facilitating rate of ADH activity was 70.3% at 50% FOB, but ALDH activity was not affected. These results revealed that FOB has a strong alcohol metabolizing activity, and fibrinolytic and nitrite scavenging activities and exhibits the angiotensin converting enzyme, $\alpha$-amylase, and $\alpha$-glucosidase inhibitory activities.

Effects of Bisphenol A on the Placental Function and Reproduction in Rats (Bisphenol A가 흰쥐의 태반 기능과 출산에 미치는 영향)

  • Lee, Chae-Kwan;Kim, Seog-Hyun;Moon, Deog-Hwan;Kim, Jeong-Ho;Son, Byung-Chul;Kim, Dae-Hwan;Lee, Chang-Hee;Kim, Hwi-Dong;Kim, Jung-Won;Kim, Jong-Eun;Lee, Chae-Un
    • Journal of Preventive Medicine and Public Health
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    • v.38 no.3
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    • pp.330-336
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    • 2005
  • Objectives : The aim of this study was to investigate the effects of bisphenol A (BPA), an estrogen-like environmental endocrine disrupter, on the placental function and reproduction in rats. The mRNA levels of the placental prolactin-growth hormone(PRL-GH) gene family, placental trophoblast cell frequency and reproductive data were analyzed. Methods : The pregnancies of F344 Fisher rats ($160g{\pm}20g$) were detected by the presence of the copulatory plug or sperm in the vaginal smear, which marked Day 0 of pregnancy. Pregnant rats were divided into three groups. The control group was intraperitoneally injected with a sesame oil vehicle. The two remaining groups were injected with 50 or 500 mg/kg B.W/day of BPA, resuspended in sesame oil, on either days 7 to 11 or 16 to 20 of pregnancy, with the rats sacrificed on either day 11 or 20, respectively. The mRNA levels of PRL-GH and Pit-1a and b isotype genes were analyzed by Northern blot hybridization and reverse transcription-polymerase chain reaction. The hormone concentrations were analyzed by radioimmunoassay, and the frequency of the placental trophoblast cells observed by a histochemical study. Reproductive data, such as the placental weight and litter size, were surveyed on day 20. The fetal weight was surveyed for 4 weeks after birth. A statistical analysis was carried out using the SAS program (version 8.1). Results : The mRNA levels of the PRL-GH gene family, such as placental lactogen I, Iv and II, prolactin like protein A, C and Cv, and decidual prolactin-related protein were significantly reduced due to BPA exposure. The mRNA levels of the Pit-1a and b isotype genes, which induce the expression of the PRL-GH gene family in the rat placenta, were also reduced due to BPA exposure. The PL-Iv and PL-II concentrations were reduced in the BPA exposed group. During the middle to last stage of pregnancy (Days 11-20), a high dose of BPA exposure reduced the frequency of spongiotrophoblast cells, which are responsible for the secretion of the PRL-GH hormones. Reproductive data, such as the placental and fetal weights and the litter size, were reduced, but that of the pregnancy period was extended in the BPA exposed compared to the control group. Conclusions : BPA disrupts the placental functions in rats, which leads to reproductive disorders.

Comparison of Enalapril Maleate Tablets on Bioavailability and the Time Course of Inhibition of Plasma Angiotensin-Converting Enzyme (Enalapril Maleate 정제의 동등성에 관한 연구 ; 약동학적 성상 및 혈장 ACE 활성도 억제 효과)

  • Jang, In-Jin;Jang, Byung-Soo;Shin, Sang-Goo;Shin, Jae-Gook;Rho, Il-Kun;Lee, Kyeong-Hun;Park, Chan-Woong
    • The Korean Journal of Pharmacology
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    • v.26 no.2
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    • pp.219-226
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    • 1990
  • Enalapril maleate tablets of two different producers were tested for bioequivalence. Enalapril is rapidly metabolized to an active metabolite, enalaprilat which inhibits angiotensin-converting enzyme (ACE). The pharmacokinetics of enalapril maleate and the time course of inhibition of plasma ACE activity after administration of the drugs were studied. Two single doses of 10mg each of enalapril maleate were administered orally to twelve male volunteers in a balanced, randomized, two-way crossover investigation. Plasma enalaprilat concentrations were determined over a 23-hour after the dose by enzyme inhibition assay and enalapril by the same method following in vitro hydrolysis. Urinary recoveries of enalapril and enalaprilat were determined for the calculation of renal clearance. Plasma ACE activity was determined by an enzyme assay. Peak plasma levels of enalapril were observed about 1 hour after the doses, and practically all enalapril had disappeared from plasma within 6 hour. Peak enalapril concentrations of both formulations were almost identical ($Vasotec^{\circledR}$, 61.38 ng/ml; $Beartec^{\circledR}$, 64.27 ng/ml). The values of the pharmacokinetic parameters of enalaprilat computed for $Vasotec^{\circledR}$ and $Beartec^{\circledR}$ tablets are presented in that order; area under the curve=330.63:320.96 $ng{\cdot}hr/ml$; peak concentration=38.63:39.43 ng/ml; time to peak=3.83:4.08 hour; elimination half-life=3.95:3.92 hours. No statistically significant difference was detected when area under the curve and all other parameters were compared. Using criteria of 95% confidence interval for the comparison of these parameters, only the upper limits of area under the curve and time to peak of enalapril were over 120%. All the parameters of enalaprilat were acceptable. Percent inhibition of plasma ACE to plasma enalaprilat concentration showed the sigmoid concentration-inhibition relationship. Time courses of plasma ACE inhibition after the administration of both formulations were quite similar. The formulations were found to be equivalent when compared on the premise that no significant difference was detected when pharmacokientic parameters and inhibition of ACE activity were compared, based on the confidence limits analysis.

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Glass Dissolution Rates From MCC-1 and Flow-Through Tests

  • Jeong, Seung-Young
    • Proceedings of the Korean Radioactive Waste Society Conference
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    • 2004.06a
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    • pp.257-258
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    • 2004
  • The dose from radionuclides released from high-level radioactive waste (HLW) glasses as they corrode must be taken into account when assessing the performance of a disposal system. In the performance assessment (PA) calculations conducted for the proposed Yucca Mountain, Nevada, disposal system, the release of radionuclides is conservatively assumed to occur at the same rate the glass matrix dissolves. A simple model was developed to calculate the glass dissolution rate of HLW glasses in these PA calculations [1]. For the PA calculations that were conducted for Site Recommendation, it was necessary to identify ranges of parameter values that bounded the dissolution rates of the wide range of HLW glass compositions that will be disposed. The values and ranges of the model parameters for the pH and temperature dependencies were extracted from the results of SPFT, static leach tests, and Soxhlet tests available in the literature. Static leach tests were conducted with a range of glass compositions to measure values for the glass composition parameter. The glass dissolution rate depends on temperature, pH, and the compositions of the glass and solution, The dissolution rate is calculated using Eq. 1: $rate{\;}={\;}k_{o}10^{(ph){\eta})}{\cdot}e^{(-Ea/RT)}{\cdot}(1-Q/K){\;}+{\;}k_{long}$ where $k_{0},\;{\eta}$ and Eaare the parameters for glass composition, pH, $\eta$ and temperature dependence, respectively, and R is the gas constant. The term (1-Q/K) is the affinity term, where Q is the ion activity product of the solution and K is the pseudo-equilibrium constant for the glass. Values of the parameters $k_{0},\;{\eta}\;and\;E_{a}$ are the parameters for glass composition, pH, and temperature dependence, respectively, and R is the gas constant. The term (1-Q/C) is the affinity term, where Q is the ion activity product of the solution and K is the pseudo-equilibrium constant for the glass. Values of the parameters $k_0$, and Ea are determined under test conditions where the value of Q is maintained near zero, so that the value of the affinity term remains near 1. The dissolution rate under conditions in which the value of the affinity term is near 1 is referred to as the forward rate. This is the highest dissolution rate that can occur at a particular pH and temperature. The value of the parameter K is determined from experiments in which the value of the ion activity product approaches the value of K. This results in a decrease in the value of the affinity term and the dissolution rate. The highly dilute solutions required to measure the forward rate and extract values for $k_0$, $\eta$, and Ea can be maintained by conducting dynamic tests in which the test solution is removed from the reaction cell and replaced with fresh solution. In the single-pass flow-through (PFT) test method, this is done by continuously pumping the test solution through the reaction cell. Alternatively, static tests can be conducted with sufficient solution volume that the solution concentrations of dissolved glass components do not increase significantly during the test. Both the SPFT and static tests can ve conducted for a wide range of pH values and temperatures. Both static and SPFt tests have short-comings. the SPFT test requires analysis of several solutions (typically 6-10) at each of several flow rates to determine the glass dissolution rate at each pH and temperature. As will be shown, the rate measured in an SPFt test depends on the solution flow rate. The solutions in static tests will eventually become concentrated enough to affect the dissolution rate. In both the SPFt and static test methods. a compromise is required between the need to minimize the effects of dissolved components on the dissolution rate and the need to attain solution concentrations that are high enough to analyze. In the paper, we compare the results of static leach tests and SPFT tests conducted with simple 5-component glass to confirm the equivalence of SPFT tests and static tests conducted with pH buffer solutions. Tests were conducted over the range pH values that are most relevant for waste glass disssolution in a disposal system. The glass and temperature used in the tests were selected to allow direct comparison with SPFT tests conducted previously. The ability to measure parameter values with more than one test method and an understanding of how the rate measured in each test is affected by various test parameters provides added confidence to the measured values. The dissolution rate of a simple 5-component glass was measured at pH values of 6.2, 8.3, and 9.6 and $70^{\circ}C$ using static tests and single-pass flow-through (SPFT) tests. Similar rates were measured with the two methods. However, the measured rates are about 10X higher than the rates measured previously for a glass having the same composition using an SPFT test method. Differences are attributed to effects of the solution flow rate on the glass dissolution reate and how the specific surface area of crushed glass is estimated. This comparison indicates the need to standardize the SPFT test procedure.

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Analysis of Nutritional Composition and Effects of Yak-sun Tea Prescription from Oriental Medicinal Herbs for Serum Lipid Levels and Homocystein Content (한약자원을 이용한 약선차의 영양성분 분석 및 약선차의 섭취가 여대생의 혈청지질수준과 호모시스테인 농도에 미치는 효과)

  • Han, Jong-Hyun;Song, You-Jin;Park, Sung-Jin;Park, Sung-Hye
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.5
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    • pp.557-564
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    • 2006
  • This research was planned and executed to evaluate how the composition of Yak-sun (oriental diet therapy) can effect health conditions of people who are suffering from diet-related diseases like obesity and hyper lipidemia by taking Yak-sun in a form of nutritional supplement with our daily meals. We produced Yak-sun tea with $Ky\hat{a}lmy\hat{a}ngja$, Kamguk, $K\hat{u}m\hat{u}nhwa$, Ch'onkung and observed nutritional composition and evaluated how this tea effects on serum lipids and homocystein concentration by clinical practices. With this observation, we found out that this tea has significant effect on increasing of HDL-cholesterol, decreasing of LDL-cholesterol and homocysteine concentration, and we think that scientific and objective evaluation was done on the components of Yak-sun tea prescription. We concluded that we could apply the components not only in a form of tea, but also in other forms of various food. The information we received from this conclusion will be a basic information on how we can apply oriental medicinal resources into other food and will also be a stepping stone for medicinal herbs to step foot in the field of functional food research, which already draws sizable attention world-wide.

Development of Unfolding Energy Spectrum with Clinical Linear Accelerator based on Transmission Data (물질투과율 측정정보 기반 의료용 선형가속기의 에너지스펙트럼 유도기술 개발)

  • Choi, Hyun Joon;Park, Hyo Jun;Yoo, Do Hyeon;Kim, Byoung-Chul;Yi, Chul-Young;Min, Chul Hee
    • Journal of Radiation Protection and Research
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    • v.41 no.1
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    • pp.41-47
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    • 2016
  • Background: For the accurate dose assessment in radiation therapy, energy spectrum of the photon beam generated from the linac head is essential. The aim of this study is to develop the technique to accurately unfolding the energy spectrum with the transmission analysis method. Materials and Methods: Clinical linear accelerator and Monet Carlo method was employed to evaluate the transmission signals according to the thickness of the observer material, and then the response function of the ion chamber response was determined with the mono energy beam. Finally the energy spectrum was unfolded with HEPROW program. Elekta Synergy Flatform and Geant4 tool kits was used in this study. Results and Discussion: In the comparison between calculated and measured transmission signals using aluminum alloy as an attenuator, root mean squared error was 0.43%. In the comparison between unfolded spectrum using HEPROW program and calculated spectrum using Geant4, the difference of peak and mean energy were 0.066 and 0.03 MeV, respectively. However, for the accurate prediction of the energy spectrum, additional experiment with various type of material and improvement of the unfolding program is required. Conclusion: In this research, it is demonstrated that unfolding spectra technique could be used in megavoltage photon beam with aluminum alloy and HEPROW program.

Inhibitory Effects of Spinach, Cabbage, and Onion Extracts on Growth of Cancer Cells (시금치, 양배추, 양파 추출물의 암세포 증식 억제 효과)

  • Lee, Hae-Nim;Shin, Seong-Ah;Choo, Gang-Sik;Kim, Hyeong-Jin;Park, Young-Seok;Kim, Sang-Ki;Jung, Ji-Youn
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.5
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    • pp.671-679
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    • 2016
  • Extracts from spinach, cabbage, and onion are known to possess various instructive characteristics, including antioxidant and anti-inflammation activities. Spinach, cabbage, and onion are consumed worldwide and represent important sources of dietary phytochemicals with proven antioxidant properties, such as flavonoids and phenolic acids. Food-derived flavonoids and phenolic compounds are expected to be promising drugs for cancer. In the present study, we investigated the effects of methanol extracts of spinach, cabbage, and onion on cell proliferation and apoptosis in human gastric and breast cancer cells. Proliferation rates of AGS, MDA-MB-231, and SK-BR-3 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The methanol extracts of spinach, cabbage, and onion inhibited proliferation of cancer cells in a dose-dependent manner. 4',6-Diamidino-2-phenylindole (DAPI) staining revealed that chromatin condensation significantly increased compared with the control. In the results of MTT assay and DAPI staining, onion extract was the most effective in inhibiting cancer cell proliferation and apoptosis. To assess changes in protein expression level by onion extract, we identified Bax (pro-apoptotic), Bcl-2 (anti-apoptotic), and poly(ADP-ribose) polymerase (PARP) protein by western blot analysis. The expression of Bax and cleaved-PARP increased, whereas expression of Bcl-2 was decreased compared with the control. These results suggest that spinach, cabbage, and onion extracts suppressed growth of human gastric cancer AGS, human breast cancer MDA-MB-231, and SK-BR-3 cells through induction of apoptosis. Among the extracts, onion extract had stronger anti-cancer and apoptosis induction effects than spinach and cabbage extracts. Further, onion extract more effectively induced apoptosis of human gastric cancer cells than human breast cancer cells. Therefore, further studies are needed to determine the anti-cancer effects of onion extracts in vivo. Onion extract can be developed as a chemopreventive or therapeutic agent for gastric cancer.

Effects of Attenuation and Scatter Corrections in Cat Brain PET Images Using microPET R4 Scanner (MicroPET R4 스캐너에서 획득한 고양이 뇌 PET 영상의 감쇠 및 산란보정 효과)

  • Kim, Jin-Su;Lee, Jae-Sung;Lee, Jong-Jin;Lee, Byeong-Il;Park, Min-Hyun;Lee, Hyo-Jeong;Oh, Seung-Ha;Kim, Kyeong-Min;Cheon, Gi-Jeong;Lim, Sang-Moo;Chung, June-Key;Lee, Myung-Chul;Lee, Dong-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.1
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    • pp.40-47
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    • 2006
  • Purpose: The aim of this study was to examine the effects of attenuation correction (AC) and scatter correction (SC) on the quantification of PET count rates. Materials and Methods: To assess the effects of AC and SC $^{18}F$-FDG PET images of phantom and cat brain were acquired using microPET R4 scanner. Thirty-minute transmission images using $^{68}Ge$ source and emission images after injection of FDG were acquired. PET images were reconstructed using 2D OSEM. AC and SC were applied. Regional count rates were measured using ROIs drawn on cerebral cortex including frontal, parietal, and latral temporal lobes and deep gray matter including head of caudate nucleus, putamen and thalamus for pre- and post-AC and SC images. The count rates were then normalized with the injected dose per body weight. To assess the effects of AC, count ratio of "deep gray matter/cerebral cortex" was calculated. To assess the effects of SC, ROIs were also drawn on the gray matter (GM) and white matter (WM), and contrast between them ((GM-WM)/GM was measured. Results: After the AC, count ratio of "deep gray matter/cerebral cortex" was increased by $17{\pm}7%$. After the SC, contrast was also increased by $12{\pm}3%$. Conclusion: Relative count of deep gray matter and contrast between gray and white matters were increased after AC and SC, suggesting that the AC would be critical for the quantitative analysis of cat brain PET data.

Induction of Growth Inhibition and Apoptosis in Human Cancer Cells by a Brown Algae Extract (갈조류 추출물에 의한 인간 암세포 성장 억제 및 세포 사멸 유도)

  • Choo, Kang-Sik;Lee, Hae-Nim;Shin, Seong-Ah;Kim, Hyeong-Jin;Park, Young-Seok;Kim, Sang-Ki;Jung, Ji-Youn
    • Journal of Life Science
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    • v.26 no.5
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    • pp.555-562
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    • 2016
  • In this study, we investigated the effects of Undaria pinnatifida (UP), Petalonia binghamiae (PB) and Punctaria latifolia (PL) extracts on the inhibition of proliferation and apoptosis in human gastric and breast cancer cells. AGS, MDA-MB-231 and SK-BR-3 cells were treated with 0, 50, 100, and 200 μg/ml concentrations of the extracts to determine their anti-proliferative effects, using the MTT assay. The UP, PB and PL extracts inhibited proliferation of AGS, MDA-MB-231 and SK-BR-3 cells in a dose-dependent manner, and the PL extract was found to be the most effective. DAPI staining was also performed to determine changes in the cell nucleus. Further, the AGS, MDA-MB-231 and SK-BR-3 cells were treated with 0, 50, 100, and 200 μg/ml of only the PL extract. DAPI staining showed increased chromatin condensation, which is indicative of apoptosis, in the 200 μg/ml group. The expression of the Bax, Bcl-2, and PARP proteins in AGS, MDA-MB-231 and SK-BR-3 cells treated with the PL extract was also determined by western blot analysis. The expression of Bax (a pro-apoptotic protein) and cleaved-PARP was increased, whereas the expression of Bcl-2 (an anti-apoptotic protein) was decreased compared with the control. These findings indicate that the PL extract may have potential as an alternative anticancer drug and nutraceutical.