• Journal of Life Science
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• v.17 no.8 s.88
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• pp.1121-1128
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• 2007

The fruits of Zanthoxylum piperitum are known as having various physiology vitality, and the abstraction ingredient of the pericarp is also known as having strong antibiotic activities against various bacteria. Therefore, this study was carried out to estimate the effect of physiology vitality when the abstraction ingredient of Z. piperitum was added in soy sauce(Chopi-kanjang) and soybean paste(Chopi-doenjang). For the antibiotic activity against the pathogens of sitotoxism such as Staphylococcus aureus, Salmonella typhimurium, Vibrio parahemolyticus, Escherichia coli 0157:H7, the extracts of the Chopi-kanjang was added 1%, 2%, 4% pericarp of Z. piperitum in the manufacturing process of soy source. According to the results, the growth of E. coli 0157:H7 and V. parahemolyticus were respectively inhibited as 70% and 50% by the Chopi-kanjang added 2% of the ingredient. For the antibiotic effects of the aforementioned Chopi-kanjang against Sal. typhimurium and Sta. aureus, the growth of those pathogens was also inhibited between 40% and 60% according to the manufacturing period of Chopi-kanjang. It was confirmed that the antibiotic activity using the mixture of the abstraction ingredient and Chopi-doenjang was lower than those of Chopi-kanjang. In order to estimate the anticancer activity using by caspase-3 activity, the mixture of the abstraction ingredient of the pericarp of Z. piperitum and Chopi-kanjang was treated to leukemia cells. According to the results, the activities of caspase-3 using the mixture added 1%, 2% and 4% of the abstraction ingredient were respectively increased as much as 4, 12, 15 times comparing with the control which was treated with the soy source only. It could be that the mixture of the abstraction ingredient of the pericarp of Z. piperitum and soy source induced apoptosis, and the mixture of the abstraction ingredient and soybean paste had no effect on the activity of caspase-3. In order to find out the death of the aforementioned cells caused by necrosis or apoptosis, DNA fragmentation in the cell was examined. U-937 cells showed apoptotic DNA fragmentation in the incubation with Chopi-kanjang extract.

• Journal of Life Science
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• v.26 no.12
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• pp.1431-1437
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• 2016

Sorghum bicolor L. is one of the important minor cereals in Asia, Africa, and the central United States, and it is considered a rich source of polyphenols, flavonoids, and dietary fiber. However, there is a lack of data on the anti-cancer activity of Sorghum in prostate cancer cells and immune activity in macrophages. This study aims to investigate the potential effects of an ethanol extract of S. bicolor L. (SE) on inducing apoptosis in RC-58T/h/SA#4 cells and immunomodulatory activity in RAW 264.7 cells. SE significantly inhibited the viability of RC-58T/h/SA#4 primary prostate cancer cells in a dose-dependent manner. The morphology of RC-58T/h/SA#4 cells treated with SE was shrunken and involved the formation of an apoptotic body and nuclear condensation. In addition, SE markedly activated caspase-8, -9, and -3; increased the protein levels of Bax, p53, cleaved PARP, and cytosolic cytochrome c; and decreased Bcl-2 protein expression. Furthermore, the inhibition of caspases in RC-58T/h/SA#4 cells with z-VAD-fmk attenuated SE-induced cell growth inhibition. The production of nitric oxide (NO) was also elevated by SE treatment, as revealed by immune response parameters. These results suggest that SE inhibits growth and induces apoptosis in primary human prostate cancer cells in a caspase-dependent manner, and it modulates the immune functions in macrophages. Therefore, Sorghum bicolor L. may be used as a functional food to prevent prostate cancer and enhance immune activity.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.87-94
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• 2008

In view of obtaining potential anticancer compounds, we studied the inhibitory activity and the cytotoxic effects of a candidate compound in cancer cells. The cytotoxic effects of cannabidiol (CBD) in vitro were evaluated in NIH3T3 fibroblasts, B16 melanoma cells, A549 lung cancer cells, MDA-MB-231 breast cancer cells, Lenca kidney cells and SNU-C4 colon cancer cells. The cells were cultured in various concentrations of CBD for 48 h and 25 ${\mu}$M of CBD for 6-36 h. The cells were observed to exhibit inhibitory effects of the cell viability in their growth, and then cytotoxicity was estimated. The inhibitory activity of CBD was increased in all cancer cells and showed especially strong increment in breast cancer cells. The cytotoxicity of CBD increased in a dose- and time-dependent manner with growth inhibition in all cancer cell lines. Also, to assess the membrane toxicity induced by CBD, we investigated lactate dehydrogenase (LDH) release. After treatment with various concentrations of CBD, LDH release rate of cancer cells was accelerated. On the other hand, in the induction of cell death, caspase-3, -8 and -9 activations were detected in cancer cells after treatment with various concentrations of CBD, and CBD effectively induced activity of caspase-3, -8 and -9 in A549 lung cancer cells, MDAMB-231 breast cancer cells and Renca kidney cells. Therefore these results suggest that CBD has a possibility of anticancer agents and anticancer effects against cancer cells by modulation of apoptotic pathway in the range of 5-80 ${\mu}$M concentration.

• Nutrition Research and Practice
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• v.8 no.2
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• pp.125-131
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• 2014

BACKGROUND/OBJECTIVES: The objective of this study was to evaluate the protective effect of black rice extract (BRE) on tert-butyl hydroperoxide (TBHP)-induced oxidative injury in HepG2 cells. MATERIALS/METHODS: Methanolic extract from black rice was evaluated for the protective effect on TBHP-induced oxidative injury in HepG2 cells. Several biomarkers that modulate cell survival and death including reactive oxygen species (ROS), caspase-3 activity, and related cellular kinases were determined. RESULTS: TBHP induced cell death and apoptosis by a rapid increase in ROS generation and caspase-3 activity. Moreover, TBHP-induced oxidative stress resulted in a transient ERK1/2 activation and a sustained increase of JNK1/2 activation. While, BRE pretreatment protects the cells against oxidative stress by reducing cell death, caspase-3 activity, and ROS generation and also by preventing ERKs deactivation and the prolonged JNKs activation. Moreover, pretreatment of BRE increased the activation of ERKs and Akt which are pro-survival signal proteins. However, this effect was blunted in the presence of ERKs and Akt inhibitors. CONCLUSIONS: These results suggest that activation of ERKs and Akt pathway might be involved in the cytoprotective effect of BRE against oxidative stress. Our findings provide new insights into the cytoprotective effects and its possible mechanism of black rice against oxidative stress.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6977-6982
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• 2014

Background: The aim of this study was to investigate the effect of a Lipofectamine2000 (Life2000) Transfection Reagent transfected psiRNA-STAT3 plasmid on 4T1 breast cancer cells. Materials and Methods: MTT was used to detect the cell proliferation of breast cancer 4T1 cells at different periods (0h, 6h, 8h, 10h); the cell cycle was assessed by flow cytometry; variation of apoptosis and mitochondrial membrane potential was observed under a fluorescence microscope; immunohistochemical staining was used to determine the expression of caspase-3 and cyclin-D1 protein. Results: An obvious effect of inhibition to 4T1 cancer cells could be observed at 8h after the psiRNA-STAT3 was transfected. Typical alterations of apoptotic morphological features were visible in the psiRNA-STAT3 treatment group. Mitochondrial membrane potential decreased significantly, the number of cells was increased in G0/G1 phase, and the number of cells was decreased in S phase, and the data were statistically significant (p<0.05), compared with the Scramble and Mock groups. Expression of caspase-3 protein was increased significantly, while that of cyclin D1 was significantly decreased. Conclusions: Life2000 transfected psiRNA-STAT3 plasmid can inhibit 4T1 tumor cell proliferation and promote apoptosis of 4T1 tumor cells, which process depends on the regulation of expression of cyclin D1 and caspase-3 protein.

• Molecules and Cells
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• v.40 no.4
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• pp.254-261
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• 2017

Glioblastomas (GBM) are very difficult to treat and their aggressiveness is one of the main reasons for this as well as for the frequent recurrences. MicroRNAs post-transcriptionally regulate their target genes through interaction between their seed sequence and 3'UTR of the target mRNAs. We previously reported that miR-296-3p is regulated by neurofibromatosis 2 (NF2) and enhances the invasiveness of GBM cells via SOCS2/STAT3. In this study, we investigated whether miR-296-5p, which originates from the same precursor miRNA as miR-296-3p, can increase the invasiveness of GBM cells. It was observed that miR-296-5p potentiated the invasion of various GBM cells including LN229, T98G, and U87MG. Through bioinformatics approaches, two genes were identified as miR-296-5p targets: caspase-8 (CASP8) and nerve growth factor receptor (NGFR). From results obtained from Ago2 immunoprecipitation and luciferase assays, we found that miR-296-5p downregulates CASP8 and NGFR through direct interaction between seed sequence of the miRNA and 3'UTR of the target mRNA. Knockdown of CASP8 or NGFR also increased the invasive ability of GBM cells, indicating that CASP8 and NGFR are involved in potentiation of invasiveness by miR-296-5p. Consistent with our findings, CASP8 was downregulated in brain metastatic lung cancer cells, which have a high level of miR-296-5p, compared to parental cells, suggesting that miR-296-5p may be generally associated with the acquisition of invasiveness. Collectively, our results implicate miR-296-5p as a potential cause of invasiveness in cancer and suggest it as a promising therapeutic target for GBM.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7713-7718
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• 2014

Background: Despite evidence suggesting roles for caspase-8 (CASP8) -652 6N del and D302H polymorphisms in prostate cancer (PCa), the association of these polymorphisms with PCa risk remains inconclusive. Therefore, a meta-analysis was performed to more precisely estimate the association of CASP8 -652 6N del and D302H polymorphisms with PCa susceptibility. Materials and Methods: A comprehensive literature search was conducted to identify all case-control studies of CASP8 D302H and -652 6N del polymorphisms and PCa risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association and the precision of the estimate, respectively. Results: Nine -625 6N del studies and 4 D302H studies were included. CASP8 -652 6N del and D302H polymorphisms were not significantly associated with PCa risk in the overall analyses. However, in the subgroup analysis stratified by ethnicity, -625 6N del was significantly associated with PCa risk in the East Asian and Indian populations under the recessive model. Furthermore, the subgroup analysis strongly suggested that D302H was associated with lower PCa risk in the Non-Indian population under the dominant model. Conclusions: In our meta-analysis, ethnic-specific differences were evident in the association of CASP8-625 6N del and D302H polymorphisms with PCa risk.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.363-372
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• 2019

Daidzein isolated from soybean (Glycine max) has been widely studied for its antioxidant and anti-inflammatory activities. However, the protective effects of 7,8,4'-trihydroxyisoflavone (THIF), a major metabolite of daidzein, on 6-hydroxydopamine (OHDA)-induced neurotoxicity are not well understood. In the current study, 7,8,4'-THIF significantly inhibited neuronal cell death and lactate dehydrogenase (LDH) release induced by 6-OHDA in SH-SY5Y cells, which were used as an in vitro model of Parkinson's disease (PD). Moreover, pretreatment with 7,8,4'-THIF significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and decreased malondialdehyde (MDA) activity in 6-OHDA-induced SH-SY5Y cells. In addition, 7,8,4'-THIF significantly recovered 6-OHDA-induced cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), increased Bax, and decreased Bcl-2 levels. Additionally, 7,8,4'-THIF significantly restored the expression levels of phosphorylated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3 beta ($GSK-3{\beta}$) in 6-OHDA-induced SH-SY5Y cells. Further, 7,8,4'-THIF significantly increased the reduced tyrosine hydroxylase (TH) level induced by 6-OHDA in SH-SY5Y cells. Collectively, these results suggest that 7,8,4'-THIF protects against 6-OHDA-induced neuronal cell death in cellular PD models. Also, these effects are mediated partly by inhibiting activation of the MAPK and PI3K/Akt/$GSK-3{\beta}$ pathways.

• Journal of the korean academy of Pediatric Dentistry
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• v.33 no.1
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• pp.13-24
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• 2006

Neuronal apoptotic events, consequently resulting in neuronal cell death, are occurred in hypoxic/ischemic condition. This cell death has been shown to be accompanied with the production of reactive oxygen species (ROS), which can attack cellular components such as nucleic acids, proteins and phospholipid. However, the underlying mechanisms of apoptosis induced in hypoxic/ischemic condition and its treatment methods are unsettled. Cobalt chloride $(CoCl_2)$ has been known to mimic hypoxic condition including the production of ROS. Epigallocatechin gallate (EGCG), a green tea polyphenol, has diverse pharmacologial activities in cell growth and death. This study was aimed to investigate the apoptotic mechanism by $CoCL_2$ and effects of EGCG on $CoCl_2-induced$ apoptosis in PC12 cells. Administration of $CoCl_2$ decreased cell survival in dose- and time-dependent manners and induced genomic DNA fragmentation. Treatment with $100{\mu}M$ EGCG for 30 min before PC12 cells were exposed to $150{\mu}M$ $CoCl_2$, being resulted in the cell viability and DNA fragmentation being rescued. $CoCl_2$ caused morphologic changes such as cell swelling and condensed nuclei whereas EGCG attenuated morphologic changes by $CoCl_2$. EGCG suppressed the apoptotic peak and a loss of ${\Delta}{\psi}_m$ induced by $CoCl_2$. $CoCl_2$ decreased Bcl-2 expression but Bax expression was not changed in $CoCl_2$- treated cells. EGCG attenuated the Bcl-2 underexpression by $CoCl_2$. $CoCl_2$ augumented the cytochrome c release from mitochondria into cytoplasm and increased caspase-8, -9 and caspase-3 activity a marker of the apoptotic executing stage. EGCG ameliorated the incruement in caspase-8, -9 and -3 activity, and cytochrome c release by $CoCl_2$ NAC (N-acetyl-cysteine), a scavenger of ROS, attenuated $CoCl_2-induced$ apoptosis in consistent with those of EGCG. These results suggest that $CoCl_2$ induces apoptotic cell death through both mitochondria- and death receptor-dependent pathway and EGCG has neuroprotective effects against $CoCl_2-induced$ apoptosis in PC12 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7261-7266
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• 2015

Breast cancer, the most common cancer in the women, is the leading cause of death. Necrotic signaling pathways will enable targeted therapeutic agents to eliminate apoptosis-resistant cancer cells. In the present study, the effect of shikonin on the induction of cell necroptosis or apoptosis was evaluated using the T-47D breast cancer cell line. The cell death modes, caspase-3 and 8 activities and the levels of reactive oxygen species (ROS) were assessed. Cell death mainly occurred through necroptosis. In the presence of Nec-1, caspase-3 mediated apoptosis was apparent in the shikonin treated cells. Shikonin stimulates ROS generation in the mitochondria of T-47D cells, which causes necroptosis or apoptosis. Induction of necroptosis, as a backup-programmed cell death pathway via ROS stimulation, offers a new strategy for the treatment of breast cancer.