• The Journal of Internal Korean Medicine
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• v.28 no.2
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• pp.230-241
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• 2007

Objective : This study was intended to ascertain the protective effect of phenolic-rich fraction (PRF) from Fructus Schisandrae on SH-SY5Y cells. Methods : PRF was obtained from the 80% ethanol extract of Fructus Schisandrae by Sepabeads SP-850 column chromatography. The neuroprotective effect of the FS PRS was investigated due to the hydrogen peroxide $(H_2O_2)-induced$ apoptosis of cultured SH-SY5Y cells. Results : Cell viability assays revealed that pretreating SH-SY5Y cells with PRF (10-200 ${\mu}g/mL$) resulted in significant dose-dependent protection against $H_2O_2-induced$ cell death. The effect was assessed by flow cytometric analysis of DNA contents using propidium iodide (PI) staining. The population of apoptotic cells was increased by 32.89% in only $H_2O_2$ (150 ${\mu}M$)-treated environment, but it was reduced by pre-treatment of FS PRF (200 ${\mu}g/mL$) to 21.61%. $H_2O_2-induced$ caspase-3 activation and PARP cleavage were reduced in FS PRF pre-treated cells, and PRF led to an apparent suppressive effect on the oxidative stress induced by reactive oxygen species (ROS). Conculsion : This study showed that Fructus Schisandrae should be useful for the treatment prevention of neurodegenerative diseases associated with elevated ROS levels.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.521-527
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• 2002

The Caesalpinia sappan is widely used in the traditional oriental herbal medicine for anti-inflammatory, antioxidant effects. The effects of water extract of C. sappan on the cell viability and induction of apoptosis were investigated in human lung cancer cell line A549. The water extract of C. sappan produced apoptotic cell death and DNA fragmentation and nucleus chromatin condensation in A549 cells. The enzyme activity of caspase-3 and protein level of actived caspase-3 were markedly increased in A549 cells treated with the water extract of C. sappan. In addition, the extract of C. sappan induced cleavage of Poly (ADP-ribose) polymerase (PARP), a known substrate for caspase-3, and dropped in cellular ATP levels. These results suggest that the extract of C. sappan exerts anticancer activity by induction of apoptosis via activation of caspase-3, cleavage of PARP protein, and depletion of cellular ATP levels in A549 cells.

• The Journal of Korean Society of Virology
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• v.30 no.2
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• pp.141-150
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• 2000

The effectiveness of noninfectious recombinant adenovirus encoding murine granulocyte-macrophage colony stimulating factor (mGM-CSF) for the treatment of Meth A fibrosarcoma was investigated in syngeneic BALB/C model. Meth A and HeLa cells transduced with the recombinant adenovirus (Ad.mGM-CSF) produced substantial amounts of mGM-CSF, while WEH1164 cells transduced with the virus did not produce mGM-CSF. Mice inoculated subcutaneously with $1{\times}10^6$ Meth A cells, followed by injection of Ad.dE1 as a control, developed large tumors that reached a mean tumor size of 22 mm by day 30. However, tumor development and tumorigenicity were significantly inhibited in mice with a single intratumoral injection of Ad.mGM-CSF at $1{\times}10^8\;pfu$. Histological examination of the tumors injected with Ad.mGM-CSF revealed dense infiltrates of neutrophils, histiocytes, lymphocytes, and eosinophils associated with apoptotic cell death. The results suggest that the recombinant adenovirus encoding GM-CSF have a potential use for cancer gene therapy.

• Toxicological Research
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• v.34 no.3
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• pp.267-279
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• 2018

Neurolathyrism is a neurodegenerative disorder characterized by spastic paraplegia resulting from the excessive consumption of Lathyrus sativus (Grass pea). ${\beta}$-N-Oxalyl-L-${\alpha},{\beta}$-diaminopropionic acid (L-ODAP) is the primary neurotoxic component in this pea. The present study attempted to evaluate the proteome-wide alterations in chick brain 2 hr and 4 hr post L-ODAP treatment. Proteomic analysis of chick brain homogenates revealed several proteins involved in cytoskeletal structure, signaling, cellular metabolism, free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated at 2 hr and later recovered to normal levels by 4 hr. Since L-ODAP mediated neurotoxicity is mainly by excitotoxicity and oxidative stress related dysfunctions, this study further evaluated the role of L-ODAP in apoptosis in vitro using human neuroblastoma cell line, IMR-32. The in vitro studies carried out at $200{\mu}M$ L-ODAP for 4 hr indicate minimal intracellular ROS generation and alteration of mitochondrial membrane potential though not leading to apoptotic cell death. L-ODAP at low concentrations can be explored as a stimulator of various reactive oxygen species (ROS) mediated cell signaling pathways not detrimental to cells. Insights from our study may provide a platform to explore the beneficial side of L-ODAP at lower concentrations. This study is of significance especially in view of the Government of India lifting the ban on cultivation of low toxin Lathyrus varieties and consumption of this lentil.

• Molecules and Cells
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• v.39 no.2
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• pp.119-128
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• 2016

Angelica polymorpha Maxim root extract (APRE) is a popular herbal medicine used for treating stomachache, abdominal pain, stomach ulcers, and rheumatism; however the effect of APRE on cancer cells has not yet been explored. Here, we examined APRE cytotoxicity seen on target neuroblastoma cells (NB) using cell viability assays, DAPI visualization of fragmented DNA, and Western blotting analysis of candidate signaling pathways involved in proliferation and apoptosis. We demonstrated that APRE reduced cell viability in NB to a greater extent than in fibroblast cells. In addition, we found that APRE could inhibit the three classes of MAPK proteins and could also down-regulate the PI3K/AKT/GSK-$3{\beta}$ activity all being relevant for proliferation and survival. APRE could also up-regulate Bax expression and down-regulate Bcl-2 and Mcl-1. With APRE treatment, depolarization of mitochondria membrane potential and activation of caspase-3 was demonstrated in the SH-SY5Y cells. We could not found increased activity of death receptor and caspase-8 as markers of the extrinsic apoptosis pathway for the APRE treated cells. In presence of a caspase-3 siRNA and a pan-caspase inhibitor, APRE could not reduce the viability of NB cells to a significant degree. So we predicted that with APRE, the intrinsic pathway was solely responsible for inducing apoptosis as we also showed that the non-caspase autophagy pathway or ER stress-ROS mediated pathways were not involved. These findings demonstrate that an intrinsic mitochondria-mediated apoptosis pathway mediates the apoptotic effects of APRE on SH-SY5Y cells, and that APRE shows promise as a novel agent for neuroblastoma therapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.950-954
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• 2005

Phellinus linteus (Berk. & M.A. Curtis) Teng, commonly referred to as Sangwhang in Korea, is a well-known species of the genus Phellinus, which attracts great attention due to its phamarcological values. P. linteus has been reported to produce anti-tumor, anti-angiogenic, anti-mutagenic and immunomodulatory activities in vivo and in vitro. However, despite extensive biochemical studies on P. linteus, the wine produced by P. linteus fermentation (WPLF) has poorly investigated. In the present study, it was compared the in vitro cytotoxic effects of WPLF with ethanol as positive control. WPLF as well as ethanol induced the inhibition of cell proliferation and morphological changes in both HepG2 and A549 cells in a concentration-dependent manner, however, WPLG treatment has less cytotoxic effects than ethanol treatment. These cytotoxic effects were associated with the induction of apoptotic cell death, but, WPLG treatment has less apoptotisis inducing effects than ethanol treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.903-907
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• 2005

Many naturally occurring plant extracts are studied for their beneficial effects for health and particularly on cancer. Apoptosis, or programmed cell death, occurs in both normal and pathological conditions, including cancer Dysregulation of apoptosis allows transformed cells to continually and uninhibitedly enter the cell cycle, thus perpetuating the sequence of mutation, genomic instability and, finally, oncogenesis. To investigate the apoptosis-inducing effect of the extract of Fructus Trichosanthis (EFT) on leukemic HL-60 cells and its mechanism, HL-60 cells in vitro in culture medium were given different doses of the extract. The inhibitory rate of cells were measured by microculture tetrazolium assay, cell apoptotic rate was detected by flow cytometry, morphology of cell apoptosis was observed by DAPI fluorescence staining, and the activations of caspases and PARP were detected using Western blotting analysis. The extract could activate the caspase-3 and caspase-8, induce PARP cleavage, inhibit growth of HL-60 cells, and cause apoptosis significantly The suppression was in dose-dependent manner. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly by DAPI fluorescence staining especially. These results will provide strong laboratory evidence of EFT for clinical treatment of acute leukemia.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.336-342
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• 2008

The resveratrol analogue piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine and reported to have anti-carcinogenic activities. To investigate the mechanism of anticarcinogenic activities of piceatannol, the effects on CYP 1 enzymes were determined in Escherichia coli membranes coexpressing recombinant human CYP1A1, CYP1A2 or CYP1B1 with human NADPH-P450 reductase. Piceatannol showed a strong inhibition of CYP1A1 and CYP1B1 in a concentration-dependent manner, and $IC_{50}$ of human CYP1A1 and CYP1B1 was 5.8 ${\mu}M$ and 16.6 ${\mu}M$, respectively. However, piceatannol did not inhibit CYP1A2 activity in the concentration of up to 100 ${\mu}M$. Piceatannol exhibited 3-fold selectivity for CYP1B1 over CYP1A1. The mode of inhibition of piceatannol was non-competitive for CYP1A1 and CYP1B1. The result that piceatannol did not inhibit CYP1B1-mediated $\alpha$-naphthoflavone ($\alpha$-NF) metabolism suggests piceatannol may act as a non-competitive inhibitor as well. In human prostate carcinoma PC-3 cells, piceatannol induces apoptosis and prevents Aktmediated signal pathway. Taken together, abilities of piceatannol to induce apoptotic cell death as well as CYP1 enzyme inhibition make this compound a useful tool for cancer chemoprevention.

• Korean Journal of Veterinary Research
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• v.52 no.2
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• pp.115-124
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• 2012

Colorectal cancer (CRC) is one of the leading causes of cancer death in western countries or in the developed countries. Zinc intake has been associated with decreased risk of CRC. We investigated the effect of zinc on the formation of colonic aberrant crypt foci (ACF) induced by azoxymethane followed by dextran sodium sulfate in mice. Five-week old ICR mice were fed with the different zinc levels (0.01, 0.1, 1 ppm) for 12 weeks. The numbers of ACF were measured in the colonic mucosa. The ACF number of HZn group was significantly low compared with LZn group or MZn group. Cytosolic superoxide dismutase activity was the highest in HZn group, while thiobarbituric acid reactive substance level for lipid peroxidation was the highest in LZn group. There was no difference in number of PCNA-positive proliferative cells among the groups. TUNEL-positive apoptotic cells were increased in HZn group compared with LZn group. The HZn group exhibited a decrease of ${\beta}$-catenin immunostaining areas compared with the LZn or MZn group. These findings indicate that dietary zinc might exert a protecting effect against colon carcinogenesis by inhibiting the development of ACF in the mice.

• Journal of Applied Biological Chemistry
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• v.63 no.1
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• pp.103-110
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• 2020

Objective: The objective of our study was to investigate anti-cancer effects of Danggui Liuhuang Decoction extract bioconverted by protease liquid coenzyme of Aspergillus kawachii (DLD-BE), compared to a non-bioconverted DLD extract (DLD-E) and determine the underlying mechanisms. Methods: DLD-E and DLD-BE were evaluated for their ability to modulate these signaling pathways and suppress the proliferation of human colorectal cancer (CRC) cells, HCT-116, LoVo, and HT-29. The anti-cancer effects of DLD-E and DLD-BE were measured by using proliferation and migration assays, cell cycle analysis, Western blots, and real-time PCR. Results: In this study, treatment with DLD-E and DLD-BE at concentrations of 25-100 ㎍/mL inhibited proliferation and migration in human CRC cells. DLD-BE induced apoptotic cell death and decreased COX-2 expression in HT-29 cells. The mechanisms of action included modulation of the AKT and extracellular-signal-regulated kinase signaling cascades along with inhibition of COX-2 expression. The results demonstrate novel anti-cancer mechanisms of DLD-BE against the growth of human CRC cells. Thus, we propose that DLD-BE can be developed as a more potent supplement to inhibit colorectal tumor growth and intestinal inflammation than DLD-E.