• Title/Summary/Keyword: apoptotic cells

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Effect of the Hexane Extract of Saussurea lappa on the Growth of HT-29 Human Colon Cancer Cells (목향 헥산추출물이 대장암세포인 HT-29 세포의 증식에 미치는 영향)

  • Kim, Eun-Ji;Park, Hee-Sook;Lim, Soon-Sung;Kim, Jong-Sang;Shin, Hyun-Kyung;Yoon, Jung-Han
    • Korean Journal of Food Science and Technology
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    • v.40 no.2
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    • pp.207-214
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    • 2008
  • In Asia Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus. Recently, in vitro cell culture studies have shown that SL has anti-ulcer, anti-inflammatory, and anti-tumor properties. To explore its potential chemopreventive and chemotherapeutic effects in colon cancer, we examined whether the hexane extract of SL (HESL) could inhibit the growth of HT-29 human colon cancer cells, and investigated the mechanisms for this effect. The cells were cultured with various concentrations (0-5 ${\mu}g/mL$) of HESL. The results indicated that HESL markedly decreased the numbers of viable HT-29 cells; whereas at the concentration of 5 ${\mu}g/mL$, HESL slightly decreased the viable cell numbers of CCD 1108Sk human skin normal fibroblasts at 72 hr. HESL substantially increased the numbers of cells in the sub G1 phase, and dose-dependently increased apoptotic cell numbers. Western blot analysis of the total cell lysates revealed that HESL increased Bax protein levels, but did not affect Bcl-2 levels. HESL induced the cleavage of poly (ADP-ribose) polymerase and caspases 8, 9, 7, and 3. This study demonstrated that HESL inhibits cell growth and induces apoptosis in HT-29 cells, which may be mediated by its ability to increase Bax levels and activate the caspase pathway. These findings may lead to the development of new therapeutic strategies for colon cancer treatment.

Induction of Apoptosis by a Combination of Paclitaxel and Carboplatin in the Presence of Hyperthermia

  • Huang, Tao;Gong, Wei-Hua;Li, Xiu-Cheng;Zou, Chun-Ping;Jiang, Guang-Jian;Li, Xu-Hui;Feng, Dian-Peng
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.81-85
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    • 2012
  • Purpose: To study enhancing effects of paclitaxel in the thermochemotherapy of osteosarcoma cell lines and related mechanisms. Materials and Methods: Paclitaxel and carboplatin were used alone or jointly on OS732 cell lines in the presence of hyperthermia. Inhibition of proliferation was measured by MTT assay and cellular changes were assessed with inverted phase contrast and fluorescence microscopy. Apoptosis was analyzed with flow cytometry (FCM) and Fas expression by immunocytochemistry. Results: At $43^{\circ}C$, one hour after the application of 10ug/ml paclitaxel and $5{\mu}g/ml$ carboplatin on OS732 cells jointly, the survival rate was 15.8% which was significantly lower than with $10{\mu}g/ml$ paclitaxel (45.8%) and $5{\mu}g/ml$ carboplatin (47.7%) respectively (P<0.01). Moreover, changes of morphology and apoptotic rates indicated that the apoptosis-inducing effect of combined application was also much enhanced, as evident also regarding Fas expression. Conclusion: Paclitaxel is conducive to thermochemotherapy of osteosarcoma cell lines, possibly accomplished by up-regulation of Fas expression with induction of apoptosis.

Potential Therapeutic Efficacy of Curcumin in Liver Cancer

  • Dai, Xin-Zheng;Yin, Hai-Tao;Sun, Ling-Fei;Hu, Xiang;Zhou, Chong;Zhou, Yun;Zhang, Wei;Huang, Xin-En;Li, Xiang-Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3855-3859
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    • 2013
  • Purpose: Liver cancer, one of the most common cancers in China, is reported to feature relatively high morbidity and mortality. Curcumin (Cum) is considered as a drug possessing anti-angiogenic, anti-inflammation and anti-oxidation effect. Previous research has demonstrated antitumor effects in a series of cancers. Materials and Methods: In this study the in vitro cytotoxicity of Cum was measured by MTT assay and pro-apoptotic effects were assessed by DAPI staining and measurement of caspase-3 activity. In vivo anti-hepatoma efficacy of Cum was assessed with HepG2 xenografts. Results: It is found that Cum dose-dependently inhibited cell growth in HepG2 cells with activation of apoptosis. Moreover, Cum delayed the growth of liver cancer in a dose-dependent manner in nude mice. Conclusions: Cum might be a promising phytomedicine in cancer therapy and further efforts are needed to explore this therapeutic strategy.

OIP5 is a highly expressed potential therapeutic target for colorectal and gastric cancers

  • Chun, Ho-Kyung;Chung, Kyung-Sook;Kim, Hee-Cheol;Kang, Jung-Eun;Kang, Min-Ah;Kim, Jong-Tae;Choi, Eun-Hwa;Jung, Kyeong-Eun;Kim, Moon-Hee;Song, Eun-Young;Kim, Seon-Young;Won, Mi-Sun;Lee, Hee-Gu
    • BMB Reports
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    • v.43 no.5
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    • pp.349-354
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    • 2010
  • Previously, we reported that overexpression of Opa (Neisseria gonorrhoeae opacity-associated)-interacting protein 5 (OIP5) caused multi-septa formation and growth defects, both of which are considered cancer-related phenotypes. To evaluate OIP5 as a possible cancer therapeutic target, we examined its expression level in 66 colorectal cancer patients. OIP5 was upregulated about 3.7-fold in tumors and over 2-fold in 58 out of 66 colorectal cancer patients. Knockdown of OIP5 expression by small interfering RNA specific to OIP5 (siOIP5) resulted in growth inhibition of colorectal and gastric cancer cell lines. Growth inhibition of SNU638 by siOIP5 caused an increase in sub-G1 DNA content, as measured by flow cytometry, as well as an apoptotic gene expression profile. These results indicate that knockdown of OIP5 may induce apoptosis in cancer cells. Therefore, we suggest that OIP5 might be a potential cancer therapeutic target, although the mechanisms of OIP5-induced carcinogenesis should be elucidated.

Post-cancer treatment of Condurango 30C, traditionally used in homeopathy, ameliorates tissue damage and stimulates reactive oxygen species in benzo[a]pyrene-induced lung cancer of rat

  • Sikdar, Sourav;Khuda-Bukhsh, Anisur Rahman
    • CELLMED
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    • v.3 no.3
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    • pp.25.1-25.8
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    • 2013
  • Homoeopathically prepared Condurango 30C is traditionally used in amelioration of certain types of cancer by homeopathic practitioners. In this study, ability of Condurango 30C in amelioration of the conventional benzo[a]pyrene (BaP)-induced lung cancer in rat has been tested. After one month of scheduled oral feeding of BaP, lung cancer is routinely developed after four months in rats. Tumorbearing rats were then treated with Condurango 30C for the next one ($5^{th}$), two ($6^{th}$) and three ($7^{th}$) months, respectively, and sacrificed. Efficacy of post-cancer treatment by Condurango 30C was evaluated against controls (placebo) by different study parameters like: body and lung weights, number and diameter of lung tumour nodules, lung architecture, DNA damage, anti-oxidant activity and reactive oxygen species (ROS) accumulation. Administration of this homeopathic remedy caused increase of body weight and decrease of lung weight, decrease in number and diameter of lung tumour nodules, particularly after one and two months of drug treatment. BaP intoxication significantly increased lipid peroxidase (LPO) with concomitant decrease in activities of different antioxidants, while Condurango 30C administration certainly reduce their levels than normal and cancerous groups, notably after one and two months' of drug treatment. Condurango 30C showed capability to induce ROS-mediated cell death evidenced from the study of ROS activities at different time-points. Further, the remedy possibly achieved its anticancer goal through mediation of DNA-nicks that possibly led cancer cells to the apoptotic pathway. Thus, Condurango 30C has anticancer potential in BaP-induced lung cancer of rats via tissue damage recovery and ROS-mediated programmed cell death.

Sperm Cytosolic Factor Activation for Bovine Somatic Cell Nuclear Transfer

  • Shin, Tae-Young
    • Journal of Embryo Transfer
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    • v.26 no.3
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    • pp.171-180
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    • 2011
  • In this study I report that in vitro development rates of bovine nuclear transfer embryos activated either with boar sperm cytosolic factor (SCF) or with ionomycin followed by cycloheximide (CHX) and subsequent in vivo developmental rates after embryo transfer are related to blastocyst quality as evaluated by apoptosis analysis. SCF was extracted from porcine semen then purified for post-activation injection after nuclear transfer. The optimal timing for SCF injection was determined to be at least 22 h post-IVM for parthenogenetic activation of bovine oocyies. A total of 364 oocytes were successfully enucleated and 268 (73.6%) fused and were injected with SCF. The survival rate of fused and injected embryos was 109/113 (96.5%) after 2 h. The cleavage rates of nuclear transfer embryos after 3 d of culture in the ionomycin/CHX treated group were significantly higher than those of the SCF-activated group (93.3% vs 81.7%, p<0.01, respectively). However, at 7 d and 9 d there was no significant difference between the total developmental rates to blastocyst for either treatment group. Total blastocyst cell numbers were also not significantly different between the two activation treatments (ionomycin/CHX: 149.5${\pm}$7.7 vs. SCF: 139.3${\pm}$4.4 cells). In contrast, the apoptotic levels in the SCF blastocysts were higher than those produced after the chemical treatment (28.2${\pm}$5.1% vs. 8.8${\pm}$0.6%, respectively). A total of 18 expanded or hatching blastocysts was transferred to nine synchronized recipients in each activation group; 5/9 (55.5%) and 2/9 (22.2%) were pregnant at 40 d in the ionomycin/CHX treatment and SCF activated group, respectively. However, only one went to term in the ionomycin/CHX treatment while none of the pregnancies from the SCF group were maintained by 90 d. In conclusion, these results suggest that SCF derived from different species is a limited activator to be used for activation after bovine nuclear transfer in lieu of a chemical activation protocol.

Effects of Rice Bran Extracts Fermented with Lactobacillus plantarum on Neuroprotection and Cognitive Improvement in a Rat Model of Ischemic Brain Injury

  • Hong, Jeong Hwa;Kim, Ji Yeong;Baek, Seung Eun;Ingkasupart, Pajaree;Park, Hwa Jin;Kang, Sung Goo
    • Biomedical Science Letters
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    • v.21 no.2
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    • pp.92-102
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    • 2015
  • This work aimed to study whether rice bran extract fermented with Lactobacillus plantarum (LW) promotes functional recovery and reduces cognitive impairment after ischemic brain injury. Ischemic brain injury was induced by middle cerebral artery occlusion (MCAO) in rats. Four groups were studied, namely the (1) sham, (2) vehicle, (3) donepezil, and (4) LW groups. Animals were injected with LW once a day for 7 days after middle cerebral artery occlusion. LW group showed significantly improved neurological function as compared to the vehicle group, as well as enhanced learning and memory in the Morris water maze. The LW group showed the greatest functional recovery. Moreover, the LW group showed an enhanced more survival cells anti-apoptotic effect in the cortex and neural cell densities in the hippocampal DG and CA1. In addition, this group showed enhanced expression of neurotrophic factors, antioxidant genes, and the acetylcholine receptor gene, as well as synaptophysin (SYP), Fox-3 (NeuN), doublecortin (DCX), and choline acetyltransferase (ChAT) proteins. Our findings indicate that LW treatment showed the largest effects in functional recovery and cognitive improvement after ischemic brain injury through stimulation of the acetylcholine receptor, antioxidant genes, neurotrophic factors, and expression of NeuN, SYP, DCX, and ChAT.

The Role of Survival Motor Neuron Protein associated with Function of Spinal Motor Neuron (척수 운동신경원의 기능과 관련된 생존운동신경원 단백질의 역할)

  • Song, Ju-Young;Kown, Young-Shil;Nam, Ki-Won;Song, Ju-Min;Kim, Dong-Hyun;Kim, Suk-Bum;Moon, Dong-Chul;Choi, Ji-Ho;Kim, Jin-Sang
    • The Journal of Korean Physical Therapy
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    • v.13 no.2
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    • pp.433-444
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    • 2001
  • This review highlights the ontogenesis and the differentiation of motor neuron in spinal cord, and introduce the survival motor neuron(SMN) which is associated with growth and survival of motor neurons. The differentiation of floor plate cells and motor neurons in the vertebrate neural tube appears to be induced by signals from the notochord. This signal is Sonic hedgehog(Shh). The early development of motor neurons involves the inductive action of Shh. The SMN gene is essential for embryonic viability. SMN mRNA is also expressed in virtually all cell types in spinal cord, including large motor neurons. The SMN protein is involved in RNA processing and during early embryonic development is necessary fer cell survival. Two SMN genes are present in 5q 13 in humans: the telomeric gene(SMNt), which is the SMA-determining gene, and the centromeric analog gene(SMNc). The majority of transcripts from the SMNt gene are full length but, major transcripts of the SMNc gene have a high degrees of alternative splicing and tend to have little or no exon 7. The SMN is involved in the RNA processing(the biogenesis of snRNPs and pre-mRNA splicing), the anti-apoptotic effects, and regulating gene expression.

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Ethanol Eluted Extract of Rhus verniciflua Stokes Showed both Antioxidant and Cytotoxic Effects on Mouse Thymocytes Depending on the Dose and Time of the Treatment

  • Lee, Jeong-Chae;Kim, Ju;Lim, Kye-Taek;Yang, Moon-Sik;Jang, Yong-Suk
    • BMB Reports
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    • v.34 no.3
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    • pp.250-258
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    • 2001
  • For a long time Rhus verniciflua Stokes (RVS) has traditionally been used as a herbal plant. It is known to contain various biological activities. Previously, a crude ethanol extract from RVS was reported to have antioxidant effects, and antiproliferative activities, on human cancer cell lines. In this report, we prepared a highly purified ethanol extract from RVS, which did not contain the urushiol derivatives, named REEE-1 ($\underline{R}$hus $\underline{e}$thanol $\underline{e}$luted $\underline{e}$xtract-1), to investigate the mechanisms of the scavenging activity of hydroxyl radicals using mouse thymocytes. The results from the deoxyribose, DNA nicking, and glucose/glucose oxidase enzyme assays showed that REEE-1 contained a strong scavenging activity of oxygen free radicals, especially of hydroxyl radicals. However, interestingly, REEE-1 also showed cytotoxicity against the thymocytes, although the effect was variable, depending on the concentrations and times of treatment. The REEE-1-mediated cytotoxicity against thymocytes, which has been used as one of the well-characterized models for apoptosis studies, was verified to be apoptotic. This was proven by the following: the appearance of DNA laddering, increases in DNA fragmentation, low fluorescence intensity in the nuclei after propidium iodide staining, and positive Annexin V staining of the cells. These results suggested that REEE-1 had both antioxidative activity and cytotoxicity against the thymocytes, although the effect of the cytotoxicity was variable, depending on the dose and time of the treatment.

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At Death's Door: Alternaria Pathogenicity Mechanisms

  • Lawrence, Christopher B.;Mitchell, Thomas K.;Craven, Kelly D.;Cho, Yang-Rae;Cramer, Robert A.;Kim, Kwang-Hyung
    • The Plant Pathology Journal
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    • v.24 no.2
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    • pp.101-111
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    • 2008
  • The fungal genus Alternaria is comprised of many saprophytic and endophytic species, but is most well known as containing many notoriously destructive plant pathogens. There are over 4,000 Alternaria/host associations recorded in the USDA Fungal Host Index ranking the genus 10th among nearly 2,000 fungal genera based on the total number of host records. While few Alternaria species appear to have a sexual stage to their life cycles, the majority lack sexuality altogether. Many pathogenic species of Alternaria are prolific toxin producers, which facilitates their necrotrophic lifestyle. Necrotrophs must kill host cells prior to colonization, and thus these toxins are secreted to facilitate host cell death often by triggering genetically programmed apoptotic pathways or by directly causing cell damage resulting in necrosis. While many species of Alternaria produce toxins with rather broad host ranges, a closely-related group of agronomically important Alternaria species produce selective toxins with a very narrow range often to the cultivar level. Genes that code for and direct the biosynthesis of these host-specific toxins for the Alternaria alternata sensu lato lineages are often contained on small, mostly conditionally dispensable, chromosomes. Besides the role of toxins in Alternaria pathogenesis, relatively few genes and/or gene products have been identified that contribute to or are required for pathogenicity. Recently, the completion of the A. brassicicola genome sequencing project has facilitated the examination of a substantial subset of genes for their role in pathogenicity. In this review, we will highlight the role of toxins in Alternaria pathogenesis and the use of A. brassicicola as a model representative for basic virulence studies for the genus as a whole. The current status of these research efforts will be discussed.