• The Journal of the Korean Society for Microbiology
• /
• v.19 no.1
• /
• pp.85-108
• /
• 1984

In order to study the relationship between resistance of tumor cells to anticancer drugs and immunologic cytotoxicity and their chromosome number, a line of cancer cells (NS-1) was exposed to BCNU and CCNU in vitro. Characteristics of the distribution of chromosome number of the survived cells were then comparatively analyzed. Effect of immune mediated cytotoxicity, i.e. complement and cell-mediated cytotoxicity, on the ploidy characteristics was observed in the same way. NS-1 cells were found to be a population of neoplastic cells of heterogeneity having 5 to 115 chromosomes per cell in metaphase. The majority of the cells were belong to the class of chromosome number 56 to 60 which were considered as the stem cell line. Dramatic changes in the distribution of chromosome number following drug treatment were not observed. However the range of chromosome distribution was slightly changed. Characteristics of chromosomal distribution of drug treated cells were not significantly varied by different doses of drug treated. Changed chromosomal distribution patterns of drug treated cells were reversible, especially the cells having 56 to 60 chromosomes recovered rapidly. Cells having 41-60 and 61-80 chromosomes among cells treated with BCNU and cells with 41-60 chromosomes after CCNU treatment were the major population which regenerated continuously. Following BCNU treatment cells having 61-80 chromosomes were not varied much whereas CCNU treatment affects the population in the same class. Chromosomal aberrations were significantly enhanced by BCNU and CCNU treatment. The frequency of chromosomal aberrations was greater in cells having more than 40 chromosomes compared with that in cells having less than 40 chromosomes. Changes in ploidy characteristics of the cells following complement mediated and cell mediated cytotoxicity were not significant. Therefore it was tentatively concluded that association of numerical distribution pattern of NS-1 cells with the response to the treatment used in this experiment was not recognized.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5243-5248
• /
• 2013

Background: Triptolide, extracted from the herb Tripteryglum wilfordii Hook.f that has long been used as a natural medicine in China, has attracted much interest for its anti-cancer effects against some kinds of tumours in recent years. Artesunate, extracted from the Chinese herb Artemisia annua, has proven to be effective and safe as an anti-malarial drug that possesses anticancer potential. The present study attempted to clarify if triptolide enhances artesunate-induced cytotoxicity in pancreatic cancer cell lines in vitro and in vivo. Methods: In vitro, to test synergic actions, cell viability and apoptosis were analyzed after treatment of pancreatic cancer cell lines with the two agents singly or in combination. The molecular mechanisms of apoptotic effects were also explored using qRT-PCR and Western blotting. In vivo, a tumor xenograft model was established in nude mice, for assessment of inhibitory effects of triptolide and artesunate. Results: We could show that the combination of triptolide and artesunate could inhibit pancreatic cancer cell line growth, and induce apoptosis, accompanied by expression of HSP 20 and HSP 27, indicating important roles in the synergic effects. Moreover, tumor growth was decreased with triptolide and artesunate synergy. Conclusion: Our result indicated that triptolide and artesunate in combination at low concentrations can exert synergistic anti-tumor effects in pancreatic cancer cells with potential clinical applications.

• Advances in Traditional Medicine
• /
• v.3 no.3
• /
• pp.141-146
• /
• 2003

The methanol extracts of the aerial parts, leaves and stem of Hypericum hookerianum were tested for in vitro cytotoxicity on selected normal and cancer cell lines and anti tumor activity using DLA cells. Cell viability and morphological changes were assessed. Among the three extracts tested, the stem extract of Hypericum hookerianum showed potent cytotoxicity against HEp-2 and RD cell lines. The $CTC_{50}$(concentration required to reduce viability by 50%) of this extract was found to be $2.02\;{\mu}g/ml$ for RD cell line, $10.25\;{\mu}g/ml$ for HEp-2 cell line and $100.06\;{\mu}g/ml$ for Vero cell line. In the clonogenic assay, no colony formation was observed up to a concentration of $100\;{\mu}g/ml$. In the short term cytotoxicity studies using DLA cells, 50% viability was observed in the concentration range of $50-100\;{\mu}g/ml$ for aerial parts, $100-200\;{\mu}g/ml$ for stem and more than $200\;{\mu}g/ml$ for leaf extracts of Hypericum hookerianum. In the long-term activity using HEp-2 cell line, no colony formation was observed over a concentration of 200 mg/ml for the stem extract. Hypericum hookerianum stem extract was fractionated into petroleum ether, chloroform, ethyl acetate and methanol soluble fractions. The petroleum ether and chloroform soluble fractions showed higher cytotoxic activity against HEp-2 cell line when compared to the other two fractions. The methanol stem extract of Hypericum hookerianum has the potential for further investigation in animal models to determine its anti-tumor activity and to identify its active principles.

• Parasites, Hosts and Diseases
• /
• v.42 no.1
• /
• pp.35-40
• /
• 2004

The nfa 1 gene was cloned from a cDNA library of pathogenic Naegleria fowleri by immunoscreening; it consisted of 360 bp and produced a 13.1 kDa recombinant protein (rNfa1) that showed the pseudopodia-specific localization by immunocytochemistry in the previous study. Based on the idea that the pseudopodia-specific Nfa1 protein mentioned above seems to be involved in the pathogenicity of N. fowleri, we observed the effect of an anti-Nfa1 antibody on the proliferation of N. fowleri trophozoites and the cytotoxicity of N. fowleri trophozoites on the target cells. The proliferation of N. fowleri trophozoites was inhibited after being treated with an anti-Nfa1 polycional antibody in a dose-dependent manner for 48 hrs. By a light microscope, CHO cells co-cultured with N. fowleri trophozoites (group I) for 48 hrs showed severe morphological destruction. On the contrary, CHO cells co-cultured with N. fowleri trophozoites and anti-Nfa1 polyclonal antibody (1:100 dilution) (group II) showed less destruction. In the LDH release assay results, group I showed 50.6% cytotoxicity, and group II showed 39.3%. Consequently, addition of an anti-Nfa1 polyclonal antibody produced a decreasing effect of in vitro cytotoxicity of N. fowleri in a dose-dependent manner.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2019.10a
• /
• pp.106-106
• /
• 2019

The leaves of Phaleria nisidai Kaneh. have been used as a beverage for tonic and immune-enhancing effect in Palau. Recently, extract of the plants showed anti-diabetic effect in clinical trial and possibility could be used as a medicine for diabetes. However, in vitro and in vivo experiments which elucidate cytotoxicity and biological mechanism have not been studied yet. To begin the series of in vitro and in vivo anti-diabetic studies, we evaluated cell viability of pancreatic beta cell lines to figure it out toxicity of the extract. The leaves of Phaleria nisidai were extracted with distilled water and 70% EtOH, and followed by evaporation and lyophilization. And, MIN6 and RIN-m5F cell lines were used for assessment of cell viability. MTT assay was adopted to evaluated a toxicity. Any of extract and concentration used in this study did not show cytotoxicity in the cell lines. Furthermore, morphological change was not observed. These results means Phaleria nisidai might be a medicinal resource when further biological and safety studies would be performed.

• Restorative Dentistry and Endodontics
• /
• v.18 no.2
• /
• pp.369-376
• /
• 1993

To know the in vitro and the in vivo cytotoicity of resin solution, resin solution was applied to cultured fibroblast and was injected into the mouse. The cytotoxic effect of resin solution was measured by MIT assay and in vivo cytotoxicity was examined after Hematoxylin and Eosin staining. The cell activity of resin solution in the concentration of 50% was significantly decreased compared to control group and 5 % group. In histopathologic study of resin solution, there were severe inflammatory cell infiltration, mild interstitial edema, trace hemorrhage, and moderate or severe muscle destruction in resin injected group. These results suggested that there might be some differences between the cell viability of fibroblast and in vivo cell cytotoxicity. Further study is needed to clarify the cytotoxicity by direct implanting of resin mass.

• Archives of Pharmacal Research
• /
• v.25 no.5
• /
• pp.718-723
• /
• 2002

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC. The present study was designed to address whether the higher activity of CKD-602 with prolonged exposure is due to delayed exhibition of cytotoxicity and/or an accumulation of anti proliferative effect on continuous drug exposure. The drug uptake study was performed to determine whether the delayed cytotoxicity is due to a slow drug accumulation in cells. CKD-602 produced a cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment had been terminated (delayed effect). Both the immediate and delayed effects of CKD-602 showed a time dependent decrease in 4IC_{50}$ values. Drug uptake was biphasic and the second equilibrium level was obtained as early as at 24hr, indicating that the cumulative and delayed antitumor effects of CKD-602 were not due to slow drug uptake. On the other hand, CKD-602 treatment was sufficient to induce delayed cytotoxicity after 4hr, however, longer treatment (＞24hr) enhanced its cytotoxicity due to the intracellular accumulation of the drug, which requires 24hr to reach maximum equilibrium concentration. In addition, $C^n$$\times$T=h analysis (n=0.481) indicated that increased exposure times may contribute more to the overall antitumor activity of CKD-602 than drug concentration. Additional studies to determine the details of the intracellular uptake kinetics (e.g., concentration dependency and retention studies) are needed in order to identify the optimal treatment schedules for the successful clinical development of CKD-602.

• Archives of Pharmacal Research
• /
• v.25 no.4
• /
• pp.457-462
• /
• 2002

Oregonin, a diarylheptanoid derivative from Alnus hirsuta Turcz, Betulaceae, was evaluated for its antitumor activity. Oregonin, known to have an antitumor function, and is a novel immunomodulator, which may augment macrophage activity. MTT assays and NO production tests were performed in order to investigate the cytotoxicity of oregonin in tumor cells and to examine its influence on macrophage in detail. In this study, the tumoricidal activity was also evaluated by a MTT assay. The cytotoxicity measurements in the oregon in-treated group both in vitro and in vivo showed a significant difference from that of the control group. In vivo, oregonin significantly increased NO production in a dose-dependent manner, and in vitro, the thioglycolate-induced inflammatory macrophages increased NO production in a dose-dependent manner after incubation. These results suggest that oregonin reacts with both the inflammatory and non-inflammatory macrophages in a similar way.

• Advances in Traditional Medicine
• /
• v.1 no.2
• /
• pp.45-51
• /
• 2000

This study was carried out to evaluate cytotoxicity of the methanol extract from Sophora flavescens Ait. against L1210 (lymphocytic leukemia) and $P388D_1$ (lymphoid neoplasma) Cells in vitro. We have determined cytotoxicity by the MTT (3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H- tetrazolium bromide) assay. The order of cytotoxicity of Sophora flavescens Ait. extracts against L1210 and $P388D_1$ cells in vitro is as follows: Fr. 4 > Fr. 3 > Fr. 5 > Fr. 2 > Fr. 1. These results suggest that the fraction 4 of the methanol extracts from Sophora flavescens Ait. may be a valuable choice for the development of antitumor agents. In order to develop an antimicrobial agent, dried Sophora flavescens Ait. was extracted with hot methanol, and then antimicrobial activity (MIC test) was investigated. In this study, the fraction 3 of the methanol extracts from the roots of S. flavescens showed strong growth inhibition activity against gram-positive and gram-negative bacteria (MIC, $3.125\;{\mu}g/ml$) such as S. mutans, S. epidermidis and P. putida. These results indicate that fractions 3 and 4 inhibit tumor cells and bacteria.

• Proceedings of the SCSK Conference
• /
• 2003.09b
• /
• pp.174-183
• /
• 2003

To obtain effective and safe topical depigmenting agents, we synthesized hydroxybenzoates, alkoxybenzoates, and 3,4,5-trimethoxycinnamate containing a thymol moiety and screened then for high-level inhibitory activity against melanin synthesis. Among them, 5-methyl-2-(methylethyl)phenyl (2Ε)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate (Melasolv)$^{TM}$ 4h, showed the most potent depigmenting effect ($IC_{50}$/ = 10$\mu$M) with low cytotoxicity ($IC_{50}$/ = 200$\mu$M). To find the inhibition mechanism of our candidate, various in vitro tests were performed such as DPPH assay, tyrosinase activity in mushroom or in culture cell and expression of tyrosinase, TRP-l and TRP-2. The result of this study suggested that 4h inhibited melanin synthesis by reducing the expression of tyrosinase and TRP-l at the transcriptional level in melan-a melanocytes.s.