• Korean Journal of Veterinary Research
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• v.37 no.3
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• pp.509-523
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• 1997

This study was carried out for investigating antitumor effects of 5-fluorouracil(5-FU), methotrexate(MTX) and retinoic acid(RA) on hepatocellular carcinoma induced in Sprague-Dawley rat. Antitumor effects were examined a flow cytometric DNA distributions by flow cytometry and stuied ATP/Pi using nuclear magnetic resorance, and the enzymatic activity of thymidylate synthetase and dihydrofolate reductase as well as contents of total collagen and sialic acid were measured with spectrophotometer. In this study, S phase fraction, contents of sialic acid and total collagen were decreased in the induced hepatocellular carcinoma treated with 5-FU and MTX, and synergistic effects of anticancer drugs were exhibited in the hepatocellular carcinoma treated with 5-FU and MTX simultaneously, and the inhibition of thymidylate synthetic and dihydrofolate reductase activity were shown in the hepatocellular carcinoma treated with 5-FU, MTX, and 5-FU and MTX simultaneously. On the other hand, the ratio of ATP/Pi were increased in all groups except group treated with RA. The experimental results suggest that above method may be valuable for evaluating antitumor effect of anticancer drugs.

• Journal of Ginseng Research
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• v.27 no.2
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• pp.47-51
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• 2003

Synergistic anticancer activities of red ginseng acidic polysaccharide (RGAS) showing immunomodulatory activity were evaluated by combined treatment with anticancer agents such as Cyclophosphamide (CY) or 5-Fluorouracil (5-FU) in experimental tumor models. The combined treatment of RGAP (100 mg/kg) and CY (3 mg/kg) exhibited 71% of survival rate in lift span of sarcoma 180-bearing mice, while single treatment of RGAP (100 mg/kg) and CY (3 or 10 mg/kg) exhibited 43, 14 and 43% of survival rates, respectively. In addition, when RGAP (100 mg/kg) was administered in combination with 5-FU (2.5 mg/kg) to sarcoma 180 tumor-bearing mice, higher survival rate was found when compared with RGAP or 5-FU treatment alone. Moreover, tumor weights in LL/2 lung carcinoma-bearing mice treated combined with RGAP (100 mg/kg) and 5-FU (5 or 10 mg/kg) was obviously decreased when compared with 5-FU alone. These results suggest that clinical trials of RGAP as an adjuvant in cancer chemotheraphy can be higly feasible.

• Journal of Microbiology and Biotechnology
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• v.10 no.3
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• pp.394-398
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• 2000

A methanol extract of the root of Peucedanum japonicum, used as a medicinal herb, showed an inhibitory effect on mammalian topoisomerase I activity. The methanol extract was suspended in ethyl acetate, and a topoisomerase I inhibitor in the organic soluble fraction was then isolated by silica gel and thin layer chromatography. The topoisomerase I inhibitory compound was indentified as falcarindiol based on the analysis of EI-MS, $^1$H and \ulcornerC NMR spectroscopy. This inhibitory showed cytotoxicity against human leukemia Jurkat T and HL60 cells with an IC\ulcorner value of 7 $\mu\textrm{g}$/ml. These results suggest the possibility of falcarindiol as a new anticancer agent which can be expected to have a synergistic effect on other anticancer drugs. In addition, the present data show that falcarindiol has antifungal, yet not antibacterial, activity.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.305-309
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• 2007

Arsenic compounds have been used to treat various diseases including cancer in oriental medicine. Arsenic trioxide ($As_2O_3,\;Trisenox^{(R)}$) has been used for the treatment of leukemia and its anti-solid tumor activity has also been reported recently. Tetra-arsenic oxide ($As_4O_6,\;TetraAs^{(R)}$) is a newly developed arsenic compound which has shown an anticancer activity in some human cancer cell lines. The purpose of this study was to evaluate the anti-gastric cancer potential of TetraAs and to search for an agent with synergistic interaction with TetraAs against human gastric cancers. We analysed anti-proliferative effect of TetraAs when given alone and in combination with other chemotherapeutic agents such as 5-FU, paclitaxel, and cisplatin in SNU-216, a human gastric cancer cell line. The $IC_{50}$ of these 4 anti-cancer drugs ranged from 5.8 nM to $7.5\;{\mu}M$ with a potency rank of order paclitaxel>TetraAs>cisplatin>5-FU. TetraAs showed 10-fold greater potency than 5-FU and cisplatin at the same effect level of $IC_{50}$. TetraAs+5-FU and TetraAs+paclitaxel showed synergistic and additive interaction, respectively. On the other hand, TetraAs with cisplatin group appeared to be strongly antagonistic. Apoptotic population was measured and compared between single and combination treatment. The apoptotic cells for the combination of TetraAs+5-FU showed significant increase compared to single TetraAs treatment. On the contrary, TetraAs+cisplatin showed less apoptotic cells compared to TetraAs or cisplatin alone treatment. Overall, our results indicate that TetraAs can be effectively combined with 5-FU or paclitaxel, but not with cisplatin for synergistic anti-cancer effect, which warrants further evaluation using in vivo models.

• Development and Reproduction
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• v.21 no.2
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• pp.139-150
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• 2017

Metformin is the most commonly prescribed anti-diabetic drug with relatively minor side effect. Substantial evidence has suggested that metformin is associated with decreased cancer risk and anticancer activity against diverse cancer cells. The tyrosine kinase inhibitor imatinib has shown powerful activity for treatment of chronic myeloid leukemia and also induces growth arrest and apoptosis in colorectal cancer cells. In this study, we tested the combination of imatinib and metformin against HCT15 colorectal cancer cells for effects on cell viability, cell cycle and autophagy. Our data show that metformin synergistically enhances the imatinib cytotoxicity in HCT15 cells as indicated by combination and drug reduction indices. We also demonstrate that the combination causes synergistic down-regulation of pERK, cell cycle arrest in S and $G_2/M$ phases via reduction of cyclin B1 level. Moreover, the combination resulted in autophagy induction as revealed by increased acidic vesicular organelles and cleaved form of LC3-II. Inhibition of autophagic process by chloroquine led to decreased cell viability, suggesting that induction of autophagy seems to play a cell protective role that may act against anticancer effects. In conclusion, our present data suggest that metformin in combination with imatinib might be a promising therapeutic option in colorectal cancer.

• Bulletin of the Korean Chemical Society
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• v.29 no.7
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• pp.1303-1310
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• 2008

Inhibitors of farnesyltransferase (FT), a key enzyme in the post-translational modifications of Ras proteins, have been extensively studied as novel anticancer agents in the preclinical stages, some of which are currently in clinical development. Previously, it has been reported that a novel FT inhibitor LB42907 inhibits Ras farnesylation in the nanomolar range in vitro. The aim of this study was to assess the antitumor efficacy of LB42907 in vitro and in vivo. Anchorage-independent growth of various human tumor cell lines was potently inhibited by treatment with LB42907, comparable to other FT inhibitors in clinical development. In the nude mouse, oral administration of LB42907 demonstrated potent antitumor activity in several human tumor xenograft models including bladder, lung and pancreas origin. Interestingly, significant tumor regression in EJ (bladder) and A549 (lung) xenografts was induced by LB42907 treatment. The effectiveness of LB42907 was also investigated in simultaneous combination with paclitaxel, vincristine, cisplatin or gemcitabine against NCI-H460, A549, and HCT116 cells in vitro using median-effect analysis. LB42907 markedly synergized with most anticancer drugs tested in this study in NCI-H460 cell. In contrast, LB42907 displayed antagonism or partial synergism with these drugs in A549 and HCT116 cells, depending on the class of combined drugs and/ or the level of cytotoxicity. Our results demonstrate that LB42907 is an effective antitumor agent in vitro and in vivo and combination of LB42907 with other chemotherapeutic drugs results in synergistic or antagonistic effects mainly in a cell line-dependent manner. Further preclinical study is warranted.

• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1195-1208
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• 2022

Silver nanoparticles (AgNPs) have potential applications in medicine, photocatalysis, agriculture, and cosmetic fields due to their unique physicochemical properties and strong antimicrobial activity. Here, AgNPs were synthesized using actinobacterial SL19 strain, isolated from acidic forest soil in Poland, and confirmed by UV-vis and FTIR spectroscopy, TEM, and zeta potential analysis. The AgNPs were polydispersed, stable, spherical, and small, with an average size of 23 nm. The FTIR study revealed the presence of bonds characteristic of proteins that cover nanoparticles. These proteins were then studied by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) and identified with the highest similarity to hypothetical protein and porin with molecular masses equal to 41 and 38 kDa, respectively. Our AgNPs exhibited remarkable antibacterial activity against Escherichia coli and Pseudomonas aeruginosa. The combined, synergistic action of these synthesized AgNPs with commercial antibiotics (ampicillin, kanamycin, streptomycin, and tetracycline) enabled dose reductions in both components and increased their antimicrobial efficacy, especially in the case of streptomycin and tetracycline. Furthermore, the in vitro activity of the AgNPs on human cancer cell lines (MCF-7, A375, A549, and HepG2) showed cancer-specific sensitivity, while the genotoxic activity was evaluated by Ames assay, which revealed a lack of mutagenicity on the part of nanoparticles in Salmonella Typhimurium TA98 strain. We also studied the impact of the AgNPs on the catalytic and photocatalytic degradation of methyl orange (MO). The decomposition of MO was observed by a decrease in intensity of absorbance within time. The results of our study proved the easy, fast, and efficient synthesis of AgNPs using acidophilic actinomycete SL19 strain and demonstrated the remarkable potential of these AgNPs as anticancer and antibacterial agents. However, the properties and activity of such particles can vary by biosynthesized batch.

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.591-598
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• 2018

Epigenetic silencing is considered to be a major mechanism for loss of activity in tumor suppressors. Reversal of epigenetic silencing by using inhibitors of DNA methyltransferase (DNMT) or histone deacetylases (HDACs) such as 5-Aza-CdR and FK228 has shown to enhance cytotoxic activities of several anticancer agents. This study aims to assess the combinatorial effects of genesilencing reversal agents (5-Aza-CdR and FK228) and oxaliplatin in gastric cancer cells, i.e., Epstein-Barr virus (EBV)-negative SNU-638 and EBV-positive SNU-719 cells. The doublet combinatorial treatment of 5-Aza-CdR and FK228 exhibited synergistic effects in both cell lines, and this was further corroborated by Zta expression induction in SNU-719 cells. Three drug combinations as 5-Aza-CdR/FK228 followed by oxaliplatin, however, resulted in antagonistic effects in both cell lines. Simultaneous treatment with FK228 and oxaliplatin induced synergistic and additive effects in SNU-638 and SNU-719 cells, respectively. Three drug combinations as 5-Aza-CdR prior to FK228/oxaliplatin, however, again resulted in antagonistic effects in both cell lines. This work demonstrated that efficacy of doublet synergistic combination using DNMT or HDACs inhibitors can be compromised by adding the third drug in pre- or post-treatment approach in gastric cancer cells. This implies that the development of clinical trial protocols for triplet combinations using gene-silencing reversal agents should be carefully evaluated in light of their potential antagonistic effects.

• Journal of Radiation Protection and Research
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• v.25 no.4
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• pp.183-190
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• 2000

Medicinal plants with synergistic effects on growth inhibition of canter cells under oxidative stress were screened in this study. Methanol extracts from 51 natural medicinal plants which were reported to have anticancer effort on hepatoma stomach cancer or colon cancers which are frequently found in Korean, were prepared and screened for their synergistic activity on growth inhibition of cancer cells under chemically-induced oxidative stress by using MTT assay. Twenty seven samples showed synergistic activity on the growth inhibition in various extent under chemically-induced oxidative stress. Among those samples, eleven samples such as Melia azedarach, Agastache rugosa, Catalpa ovata, Prunus persica, Sinomenium acutum Pulsatilla koreana, Oldenlandia diffusa, Anthriscus sylvestris, Schizandra chinensis, Gieditsia sinensis, Cridium officinale, showed decrease in $IC_{50}$ values more than 50%, other 16 samples showed decrease in $IC_{50}$ values between 50-25%, compared with the value acquired when medicinal plant sample was used alone. Among those 11 samples, extract of Catalpa ovata showed the highest activity. $IC_{50}$ values were decrease to 61% and 28% when carcinoma cells were treated with Catalpa ovata extract in combination of 75 and 100 uM of hydrogen peroxide, respectively.

• Journal of Life Science
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• v.17 no.12
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• pp.1634-1640
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• 2007

The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), nitric oxide (NO) scavenging activities and ferric- reducing/antioxidant power (FRAP) assay against extracts of Kalopanax pictus (KP) were measured. Radical scavenging and antioxidant activities were increased depend on the concentration and the effects were enhanced by ascorbic acid (AA). KP extracts and AA had a good anti-proliferating activity against HepG2 cells by MTT assay and induces cells apoptosis, which was demonstrated by flow cytometric analysis. KP extracts and AA caused the arrest of cell-cycle progression at either G0-G1-phase or G2/M-phase, which might be depending upon the KP extracts concentration. In addition, KP extracts and AA are effective in enhancing immunity and nitric oxide production by RAW 264.7 macrophages cells. KP extracts and AA inhibited tumor cell growth and exerted antioxidant effects as compared to controls. These results demonstrate that simultaneous AA and KP extracts treatment could be useful in preventing the oxidative damage and anti-proliferating HepG2 cells, and are effective in enhancing immunomodulatory and antioxidant activity.