• Herbal Formula Science
• /
• v.25 no.3
• /
• pp.391-412
• /
• 2017

Objective : In this study, we searched the experimental research about combined treatment of anticancer drug and herbal medicine for killing or inhibiting proliferation of Cancer cells searched in OASIS and KISS. This study aimed to analyze the experimental research paper about anticancer drug combined treatment with herbal medicine. Methods : We collected the research paper including killing or inhibiting proliferation of Cancer cells in OASIS and KISS using keyword anticancer drug with herbal medicine, tumor suppressor with herbal medicine, inhibition of Cancer with herbal medicine and combined treatment with herbal medicine. Assorting by cancer cells, we analyzed experimental results cancer cell viability, anticancer drug dosage, tumor weight and survival rate. Also, we checked the effects of herbal medicine on cancer and additive effect reducing side effect of anticancer drug. Results : Total 45 studies were selected. 38 studies reported combined treatment of anticancer drug and herbal medicine was more effective than only anticancer drug. The death of cancer cells was synergistically induced by the cotreatment of anticancer drug and herb extracts. The studies suggest that the cotreatment of anticancer drug and herb extracts could reduce side effect of anticancer drug. In addition, some studies reported cotreatment mechanism like apoptotic death signal processes. In combined treatment of anticancer drug and herb extracts, The expression of Fas/Fas L, Bax, Bcl2, Caspase-3 etc.. was markedly increased in cancer cells. Conclusions : Our results suggest that anticancer drug combined treatment with herbal medicine could be efficient for killing or inhibiting proliferation of cancer cells. However, this paper had some limitation as follows: First, collected studies have been published only for korean journal. Second, results of research and effects of combined treatment are not collected objectively. To solve these problems, more objective and balanced studies should be performed.

• The Journal of Internal Korean Medicine
• /
• v.28 no.4
• /
• pp.694-708
• /
• 2007

Objectives : Jageum-Jung is used as an anti-cancer agent in oriental medicine, but the mechanism by which it induces cell death in cancer cells is still unclear. The purpose of this study was to investigate the effects of Jageum-Jung on apoptosis and cell cycle arrest in HepG2 hepatoma cells. Methods : Various cancer cell lines including HepG2, C6 glioma, SH-SY5Y, PANC-1, and MCF-7 cells, were used. Apoptosis was determined by DAPI nuclei staining and flow cytometry in HepG2 cells treated with various concentrations (from 25 to 200 ${\mu}g/ml$) of $H_2O$ extract of Jageum-Jung (JGJ) for 48 hrs. Expression of cell cycle arrest mediators including Rb, p53, p21, cyclin B1, cdk4, and cyclin E proteins were measured by Western blot analysis. To estimate intracellular hydrogen peroxide levels and intracellular nitric oxide levels, HepG2 cells were stained with DCFH-DA dye and DAF dye, subjected on flow cytometric analysis. Results : 1. Jageum-Jung decreased the viability of HepG2 cells in a dose-dependent manner. 2. Jageum-Jung induced the catalytic activation of caspase-3 in HepG2 cells. 3. Jageum-Jung increased the intracellular hydrogen peroxide and NO in HepG2 cells. 4. Jageum-Jung increased the expression of Rb, p53 and p21 in HepG2 cells. 5. Jageum-Jung induced the expression of cyclin B1, cdk4, and cyclin E in HepG2 cells. Conclusions : Taken together, we suggest that Jageum-Jung exhibits cytotoxic effects on HepG2 cells, causing apoptosis and cell cycle arrest. The results showed that Jageum-Jung may do so by regulating the expression of specific target molecules that promote efficient apoptotic cell death following $G_2$/M phase arrest in a dose-dependent manner.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.6
• /
• pp.2753-2758
• /
• 2014

Background: GC-binding factor 2 (GCF2) is a transcriptional regulator that represses transcriptional activity of the epidermal growth factor receptor (EGFR) by binding to a specific GC-rich sequence in the EGFR gene promoter. In addition to this function, GCF2 has also been identified as a tumor-associated antigen and regarded as a potentially valuable serum biomarker for early human hepatocellular carcinoma (HCC) diagnosis. GCF2 is high expressed in most HCC tissues and cell lines including HepG2. This study focused on the influence of GCF2 on cell proliferation and apoptosis in HepG2 cells. Materials and Methods: GCF2 expression at both mRNA and protein levels in HepG2 cells was detected with reverse transcription (RT) PCR and Western blotting, respectively. RNA interference (RNAi) technology was used to knock down GCF2 mRNA and protein expression. Afterwards, cell viability was analyzed with a Cell Counting Kit-8 (CCK-8), and cell apoptosis and caspase 3 activity by flow cytometry and with a Caspase 3 Activity Kit, respectively. Results: Specific down-regulation of GCF2 expression caused cell growth inhibition, and increased apoptosis and caspase 3 activity in HepG2 cells. Conclusions: These primary results suggest that GCF2 may influence cell proliferation and apoptosis in HepG2 cells, and also provides a molecular basis for further investigation into the possible mechanism at proliferation and apoptosis in HCC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.22
• /
• pp.9655-9660
• /
• 2014

Background: Nigella Sativa (NS) is an herb from the Ranunculaceae family that exhibits numerous medicinal properties and has been used as important constituent of many complementary and alternative medicines (CAMs). The ability of NS to kill cancer cells such as PC3, HeLa and hepatoma cells is well established. However, our understanding of the mode of death caused by NS remains nebulous. The objective of this study was to gain further insight into the mode and mechanism of death caused by NS in breast cancer MCF-7 cells. Materials and Methods: Human breast cancer cells (MCF-7) were treated with a methanolic extract of NS, and a dose- and time-dependent study was performed. The $IC_{50}$ was calculated using a Cell Titer $Blue^{(R)}$ viability assay assay, and evidence for DNA fragmentation was obtained by fluorescence microscopy TUNEL assay. Gene expression was also profiled for a number of apoptosis-related genes (Caspase-3, -8, -9 and p53 genes) through qPCR. Results: The $IC_{50}$ of MCF-7 cells was $62.8{\mu}L/mL$. When MCF-7 cells were exposed to $50{\mu}L/mL$ and $100{\mu}L/mL$ NS for 24h, 48h and 72h, microscopic examination (TUNEL assay) revealed a dose- and time-dependent increase in apoptosis. Similarly, the expression of the Caspase-3, -8, -9 and p53 genes increased significantly according to the dose and time. Conclusions: NS induced apoptosis in MCF-7 cells through both the p53 and caspase pathways. NS could potentially represent an alternative source of medicine for breast cancer therapy.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.6
• /
• pp.325-331
• /
• 2003

3-Nitropropionic acid (3-NP) inhibits electron transport in mitochondria, leading to a metabolic failure. In order to elucidate the mechanism underlying this toxicity, we examined a few biochemical changes possibly involved in the process, such as metabolic inhibition, generation of reactive oxygen species (ROS), DNA strand breakage, and activation of Poly(ADP-ribose) polymerase (PARP). Exposure of SK-N-BE(2)C neuroblastoma cells to 3-NP for 48 h caused actual cell death, while inhibition of mitochondrial function was readily observed when exposed for 24 h to low concentrations (0.2${\sim}$2 mM) of 3-NP. The earliest biochemical change detected with low concentration of 3-NP was an accumulation of ROS (4 h after 3-NP exposure) followed by degradation of DNA. PARP activation by damaged DNA was also detectable, but at a later time. The accumulation of ROS and DNA strand breakage were suppressed by the addition of glutathione or N-acetyl-L-cysteine (NAC), which also partially restored mitochondrial function and cell viability. In addition, inhibition of PARP also reduced the 3-NP-induced DNA strand breakage and cytotoxicity. These results suggest that oxidative stress and activation of PARP are the major factors in 3-NP-induced cytotoxicity, and that the inhibition of these factors may be useful in protecting neuroblastoma cells from 3-NP-induced toxicity.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2018.10a
• /
• pp.103-103
• /
• 2018

Oenothera biennis, commonly known as evening primrose, a potential source of natural bioactive substances: flavonoids, steroids, tannins, fatty acids and terpenoids responsible for a diverse range of pharmacological functions. However, whether extract prepared from aerial part of O. biennis (APOB) protects skin against oxidative stress remains unknown. To investigate the protective effects of APOB against oxidative stress-induced cellular damage and elucidated the underlying mechanisms in the HaCaT human skin keratinocytes. Our results revealed that treatment with APOB prior to hydrogen peroxide ($H_2O_2$) exposure significantly increased viability, and the highest DPPH radical-scavenging activities and reducing power of HaCaT cells. APOB also effectively attenuated H2O2-induced comet tail formation and inhibited the $H_2O_2$-induced phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V-positive cells. In addition, APOB exhibited scavenging activity against intracellular reactive oxygen species (ROS) accumulation and restored the mitochondrial membrane potential loss by $H_2O_2$. Moreover, $H_2O_2$ enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase (PARP), a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with APOB. Furthermore, APOB increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). According to our data, APOB is able to protect HaCaT cells from $H_2O_2$-induced DNA damage and cell death through blocking cellular damage related to oxidative stress through a mechanism that would affect ROS elimination and activating the Nri2/HO-1 signaling pathway.

• Tuberculosis and Respiratory Diseases
• /
• v.57 no.3
• /
• pp.250-256
• /
• 2004

Background : Bacterial infections in diabetic patients are an important cause of increased morbidity and mortality. It has been reported that bacterial infections in diabetics showed more impaired PMN functions such as reduced PMN respiratory burst and decreased microbicidal activity in inflammed tissues. Also, apoptosis(programmed cell death) is postulated to be a key mechanism for neutrophil elimination. It is very important that PMN apoptosis keeps the balance from an area of inflammation. Actuallly, as little was known about PMN apoptosis and respiratory burst in diabetes, we investigated PMN apoptosis and hydrogen peroxide production after endotoxin exposure. Methods : Peripheral venous blood samples were collected by routine venipuncture from healthy volunteers and diabetics to harvest neutrophils. We respectively measured the PMN apoptosis, the production of hydrogen peroxide, and the cell viability. Results : Normal neutrophils showed a tendency to decreased apoptosis after endotoxin treatment. In patients with diabetes, PMN apoptosis was significantly decreased compared with healthy controls. In addition, the LPS-induced neutrophils in diabetics demonstrated more decreased apoptosis. However, the production of hydrogen peroxide was not different between groups. Conclusion : These observations suggest that the decreased PMN apoptosis in diabetics with endotoxin exposure may also affect the increased susceptibility and severity of infections.

• Toxicological Research
• /
• v.21 no.4
• /
• pp.347-353
• /
• 2005

Eukaryotic initiation factor 4E (elF4E) is a key element for cap-dependent protein translation controlled by affinity between elF4E and 4E-binding protein 1 (4E-BP1). Rapamycin can also affect protein translation by regulating 4E-BP1 phosphorylation. Tobacco-specific nitrosamine, 4(N-methyl-N-nitrosamino )-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen, but its precise lung cancer induction mechanism remains unknown. Relative roles of cap-dependent and -independent protein translation in terms of NNK-induced lung carcinogenesis were elucidated using normal human bronchial epithelial cells. NNK concentrations applied in this study did not decrease cell viability. Addition of NNK restored rapamycin-induced decrease of protein synthesis and rapamycin-induced phosphorylation of 4E-BP1, and increased expression levels of mTOR, ERK1/2, p70S6K, and Raf-1 in a concentration-dependent manner. NNK also caused perturbation of normal cell cycle progression. Taken together, NNK might cause toxicity through the combination of restoration of 4E-BP1 phosphorylation and increase of elF4E as well as mTOR protein expression, interruption of Raf1/ERK as well as the cyclin G-associated p53 network. Our data could be applied towards elucidation of the molecular basis for lung cancer treatment.

• Journal of Life Science
• /
• v.27 no.3
• /
• pp.267-274
• /
• 2017

The patient with end-stage renal disease show several nervous complications. The factors contributing to the nervous complications are still incompletely characterized. Cyanate, known as one of the uremic toxins, is derived spontaneously from urea. To investigate the mechanism of cyanate-induced effect on C6 glioma cells, the glioma cells were treated with 0, 1, 5, 10, 20 and 40 mM cyanate. There was a dose-dependent decrease in cell viability and the decreased number of cell was observed in glioma cells by treatment with cyanate. Western blot showed the down- regulation of procaspase-3, which means up-regulation of caspase-3, and the up-regulation of caspase-8, but the down-regulation by cyanate. In addition, cDNA microarray showed 934 down-regulated genes and 165 up-regulated genes on 1,099 genes in cyanate treated group. Treatment with cyanate led to 16 down-regulated genes and 6 up-regulated genes on apoptosis category, and especially heat shock 70 kD protein 1A gene on the category of apoptosis was significantly up-regulated. These results suggest that cyanate can induce apoptosis through caspase-8 and caspase-3 in glioma cells and decrease of gene expression including apoptosis category in glioma cells. These effects of cyanate may play a role in the nervous complications of patient with end-stage renal disease.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.8
• /
• pp.3581-3586
• /
• 2014

Aim: To investigate the effects of tetramethypyrazine (TMP) on proliferation and apoptosis of the human gastric carcinoma cell line 7901 and its possible mechanism of action. Methods: The viability of TMP-treated 7901 cells was measured with a 3-(4, 5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) and cell apoptosis was analyzed by flow cytometry. The distribution of cells in different phases of cell cycle after exposure of TMPs was analyzed with flow cytometry. To investigate the molecular mechanisms of TMP-mediated apoptosis, the expression of NF-${\kappa}Bp65$, cyclinD1 and p16 in SGC-7901 cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Results: TMP inhibited the proliferation of human gastric carcinoma cell line 7901 in dose and time dependent manners. Cell growth was suppressed by TMP at different concentrations (0.25, 0.5, 1.0, 2.0 mg/ml), the inhibition rate is 0.46%, 4.36%, 14.8%, 76.1% (48h) and 15.5%, 18.5%, 41.2%, 89.8% (72h) respectively. When the concentration of TMPs was 2.0mg/ml, G1-phase arrest in the SGC-7901 cells was significant based on the data for cell cycle distribution. RT-PCR demonstrated that NF-${\kappa}Bp65$ and cyclin D1 mRNA expression was significantly down-regulated in 7901 cells treated with 2.0 mg/ml TMP for 72h (p<0.05), while the p16 mRNA level was up-regulated (p<0.05). The protein expression of NF-${\kappa}Bp65$ and cyclin D1 decreased gradually with the increase in TMP concentration, compared with control cells (p<0.05), while expression of protein p16 was up-regulated (p<0.01). Conclusion: TMP exhibits significant anti-proliferative and pro-apoptotic effects on the human gastric carcinoma cell line SGC-7901. NF-${\kappa}Bp65$, cyclinD1 and p16 may also play important roles in the regulation mechanisms.