• YAKHAK HOEJI
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• v.46 no.2
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• pp.108-112
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• 2002

Drug resistance is one of the most significant impediments to successful chemotherapy of cancer. Multidrug-resistance (MDR) is characterized by decreased cellular sensitivity to anticancer agents due to the overexpression of P-glycoprotein. By employing a resistant subline of HCT15 to adriamycin (CL02), we undertook the screening for agents which were effective to multidrug-resistant cancer cells. As a result, a myxobacterial strain JW150 was selected for study since an activity against CL02 cells was discovered in the strain. Cytotoxicity-guided fractionation of the culture broth led to the isolation of cystothiazole A and melithiazole F. The producing organism was identified as Myxococcus stipitatus by taxonomic comparison with type strains of Myxococcus sp. as well as its morphological and physiological characteristics. Cystothiazole A and melithiazole F demonstrated potent cytotoxicity against certain human cancer cells with $IC_{50}$ values ranging from 0.03~ $0.72{\mu}{\textrm{g}}$/ml. Both compounds were interestingly as active against drug-resistant sublines CL02 and CP70 as against the corresponding parental cells.

• Bulletin of the Korean Chemical Society
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• v.28 no.11
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• pp.1931-1938
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• 2007

Analyzed are recent advances in design of novel boronared conjugates of synthetic and natural porphyrins and chlorins. These compounds showed high efficacy as cytotoxic agents for tumor cells in culture and as phototoxins in photodynamic therapy of tumor xenografts. Thus, boronated porphyrins and chlorins emerge as promising class of anticancer agents with potentially multiple advantages: the chemotherapeutic drugs alone and photo- and radiosensitizers in binary treatments.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.4
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• pp.480-484
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• 2008

The incidence of aspergillosis infections in the maxillary sinus has increased recently, because of overuse of antibiotics, steroids, anticancer agents, immunosuppressant, antimetabollites, and uncontrolled diabetes mellitus. The clinical features of maxillary sinus aspergillosis include pain, swelling and foul odor nasal excretion. This needs to be differentiated from bacterial maxillary sinusitis, and surgical treatment with antifungal agents are suggested. Recently, we treated two patients with maxillary sinus aspergillosis surgically (Caldwell Luc operation) and with antifungal agents(itraconazole). The results were satisfactory so we report these cases with literature review.

• Korean Journal of Pharmacognosy
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• v.28 no.4
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• pp.209-214
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• 1997

This study was carried out to find new antitumor agents from plant resource. Three cytotoxic agents were isolated from the root of Dictamnus albus by hexane extraction, silica gel column chromatography and HPLC. They were identified to be dictamnine $(C_{12}H_9NO_2)$, preskimmianine $(C_{17}H_{21}NO_4)$ and fraxinellone $(C_{14}H_{16}O_3)$ on the basis of spectroscopic evidences. In this study, it was newly found that these compounds possess a cytotoxic activity against lung lymphoma L1210 cell line. Among them. Preskimmianine was the most potent against the lymphoma L1210 with a $IC_{50}$ of $3.125\;{\mu}g/ml\;(10.3\;{\mu}M)$. Toxicity of preskimmianine against normal Iymphocyte was observed at the concentration of $50\;{\mu}g/ml\;(165\;{mu}M)$. These results support the pharmacological role of D. albus, a herb known as Paeksun in Korea and used as an anticancer agent in folk medicine.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.321-325
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• 1996

Aiming at the development of anticancer agents by modification of phenolic benzo[c]phenanthridine alkaloid, additional hydroxyl group was put on C10 position of fagaridine (1) by a biomimetic synthetic procedure to afford 10-hydroxyfagaridine (12). All of the synthetic intermediates were also screened in vitro antitumor activities against five different cell lines as well as 12. Among them the representative cytotoxic results are shown as follows; P-quinone (11) $[ED_50;(A549=0.22; {\mu}g/ml)$, $(HCT;15=0.21 {\mu}g/ml)$, fagaridine (1) $(HCT;15=0.41 {\mu}g/ml)$, olefin (6) $(HCT; 15=0.06 {\mu}g/ml)$, acetal (7) $(SKMEL-2=0.07 {\mu}g/ml)$, dihydrofagaridne (10) $(A549=0.38 {\mu}g/ml)$, 10-hydroxyfagaridine (12) $(A 549=0.45{\mu}g/mi)$. From these observation three main remarks can be drawn; (i) the iminium part of benzo[c]phenanthridine is not essential for showing acitvities, (ii) the additional hydroxyl group did not contribute to enhance the cytotoxicity, (iii) the 3-arylisoquinolin-1(2H)-one derivatives were found to display significant in vitro antitumor activity.

• International Journal of Industrial Entomology and Biomaterials
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• v.8 no.2
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• pp.135-138
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• 2004

In order to find potential anticancer agents, we extracted pheophytin from silkworm feces according to various dry and storage methods such as sun dry, shade dry, fresh freezing dry and freezing dry after freezing storage (for 1∼3 years). The pheophytin extracts, mainly 10-hydroxypheophytin a, little b, of various storage silkworm feces were analyzed by reversed-phase high-performance liquid chromatography with photodiode array and fluorescence detection. The content of those pheophytih in old silkworm for 3 years (freezing storage and freezing dried in use, or freezing dried and cold storage) was better than others. The cytotoxicity of the pheophytin extracts and ethanol extracts of various storage silkworm feces were measured using Jurkat cells originated from human leukemia, using dye uptake assay (MTT) in order to find effective photodynamic therapeutic agents. The anticancer activity of those pheophytin extracts in various storage methods showed little difference among them. But ethanol extracts of fresh freezing dried silkworm in the current year was good cytotoxic activity than those of any other silkworm feces. With regards to these results, fresh ethanol extracts of silkworm feces were better than old ones. On the other hands, the pheophytin extracts of old silkworm feces contained the highest percentage of pheophytin content and showed good cytotoxicity against cancer cells by changing the pheophytin into pheophobide in the degradative process.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.105-112
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• 2003

Selective COX (cyclooxygenase)-2 inhibitors including celecoxib have been shown to induce apoptosis and cell cycle changes in various tumor cells. New inhibitors are recently being developed as chemomodulating agents. We evaluated celecoxib and screened 150 synthetic compounds for anti-proliferative activities in vitro. Effects of celecoxib on COX activity, cell growth, cell cycle distribution, and apoptosis induction were determined in A549 COX-2 overexpressing human non-small cell lung cancer (NSCLC) cells. The COX inhibition of celecoxib increased with concentration up to 82% at $1\;{\mu}M$ after 24 hr exposure. Forty ${\mu}M$ and $50\;{\mu}M$ of ce1ecoxib induced $G_1$ arrest, and TUNEL-positive apoptotic cells, respectively. Among 150 compounds, several compounds were selected for having greater COX-2 inhibitory activity and higher selectivity than celecoxib with growth inhibitory activity. Celecoxib showed concentration-dependent COX inhibitory activity, and ability to induce cell cycle arrest and apoptosis in human NSCLC cells in vitro. Among synthetic analogues screened, several compounds showed promising in vitro activity as COX-2 inhibitory anticancer agents, which warrant further evaluation in vitro and in vivo.

• Korean Journal of Clinical Pharmacy
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• v.28 no.1
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• pp.65-75
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• 2018

Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. Methods: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. Results: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. Conclusion: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.

• CELLMED
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• v.3 no.1
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• pp.9.1-9.10
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• 2013

In traditional systems of medicine including homeopathy, the Condurango extract (Con) is often used to cure stomach cancer mainly, without having any scientific validation of its anti-cancer ability. Con has therefore been tested against non-small-cell lung cancer cells (NSCLC) A549 and NCI-H522 (H522) known to contain the KRAS mutation, making them resistant to most chemotherapeutic agents. As cancer cells generally defy cytotoxicity developed by chemopreventive agents and escape cell death, any drug showing the capability of preferentially killing cancer cells through apoptosis is worth consideration for judicious application. A549 and H522 cells were exposed to $0.35{\mu}g/{\mu}l$ and $0.25{\mu}g/{\mu}l$ of Con, respectively, for 48 h and analysed based on various protocols associated with apoptosis and DNA damage, such as MTT assay to determine cell viability, LDH assay, DNA fragmentation assay, comet assay, and microscopical examinations of DNA binding fluorescence stains like DAPI, Hoechst 33258 and acridine orange/ethidium bromide to determine the extent of DNA damage made in drug-treated and untreated cells and the results compared. Changes in mitochondrial membrane potential and the generation of reactive oxygen species were also documented through standard techniques. Con killed almost 50% of the cancer cells but spared normal cells significantly. Fluorescence studies revealed increased DNA nick formation and depolarized membrane potentials after drug treatment in both cell types. Caspase-3 expression levels confirmed the apoptosis-inducing potential of Con in both the NSCLC lines. Thus, overall results suggest considerable anticancer potential of Con against NSCLC in vitro, validating its use against lung cancer by practitioners of traditional medicine including homeopathy.

• YAKHAK HOEJI
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• v.47 no.2
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• pp.57-68
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• 2003

Under the active search for biologically active novel agents for cancer prevention and treatment, some agents have been found from plants which are easily available. Our previous research on them revealed that C. annuum L. var. angulosum Mill have high antiproliferating effect on cancer cells. However, it has not been known whether the anticancer efficacy is different according to each part of C. annuum L. var. angulosum Mill or whether it can be changed by timing of harvest or solvent for extraction. Thus we compared the efficacy of each part of C. annuum L. var. angulosum Mill and assessed how much difference in the efficacy can be made according to the time of harvest or solvents for extraction. We observed the morphologic change and apoptosis 48 hr after treatment with the extract of each part of C. annuum L. var. angulosum Mill in MCF-7 mammary gland adenocarcinoma cells and human hepatoma cells. We also counted cancer cells by trypan blue method and MTT method to check the cytotoxicity. The leaf extract showed the highest anticancer effect among all the parts of C. annuum L. var. angulosum Mill; 50％ and 70％ reduction in the number of cancer cells was observed at 25 $\mu\textrm{g}$/mι and 50 $\mu\textrm{g}$/mι, respectively. It was more than 2 times as potent as 5-fluorouracil (5-FU). We found chromosomal fragmentation, clumping, and destuction by PI staining, and DNA fragmentation by electrophoresis. In conclusion, this study suggests that leaf extraction using water as solvent has the highest antiproliferative and apoptotic activity in cancer cells compared with other parts of extraction.