• The Korean Journal of Physiology and Pharmacology
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• 제13권2호
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• pp.115-121
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• 2009

Functional defects in mitochondria are involved in the induction of cell death in cancer cells. We assessed the toxic effect of camptothecin against the human cervical and uterine tumor cell line SiHa with respect to the mitochondria-mediated cell death process, and examined the combined effect of camptothecin and anticancer drugs. Camptothecin caused apoptosis in SiHa cells by inducing mitochondrial membrane permeability changes that lead to the loss of mitochondrial membrane potential, decreased Bcl-2 levels, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH. Combination of camptothecin with other anticancer drugs (carboplatin, paclitaxel, doxorubicin and mitomycin c) or signaling inhibitors (farnesyltransferase inhibitor and ERK inhibitor) did not enhance the camptothecin-induced cell death and caspase-3 activation. These results suggest that camptothecin may cause cell death in SiHa cells by inducing changes in mitochondrial membrane permeability, which leads to cytochrome c release and activation of caspase-3. This effect is also associated with increased formation of reactive oxygen species and depletion of GSH. Combination with other anticancer drugs (or signaling inhibitors) does not appear to increase the anti-tumor effect of camptothecin against SiHa cells, but rather may reduce it. Combination of camptothecin with other anticancer drugs does not seem to provide a benefit in the treatment of cervical and uterine cancer compared with camptothecin monotherapy.

• 대한한의학회지
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• 제16권2호
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• pp.386-413
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• 1995

In order to prove the antitumor effect of Taraxaci Herba experimentally, studies were done. The antitumor effect against hepatic cancers such as Hep G2. Hep 3B & PLC and also the synergstric action was evaluated in the combined treatment with anticancer drugs using chiefly for liver cancer. such as. The results were obtained as follows: 1.$IC_{50}$ against Hep G2. Hep 3B and PLC was $15.5{\mu}g/ml.\;25.4{\mu}g/ml,\;31.25{\mu}g/ml$ in Mitomycin C(MMC), $92.5{mu}g/ml,\;50.2{\mu}g/ml,\;62.5{\mu}g/ml $in cisplatin(CPT) and 125 in 5-flurouracil(5-FU) respectively. 2. In cytotoxic effect against Hep G2 every fractions showed the anti tumor effect as compared with the data of control but EE fraction of Taraxaci Herba was most effective and also hexane fraction was most effective in the combined treatment with anticancer drugs. 3. In cytotoxic effect against Hep 3B every fractions showed the antitumor effect as compared with the data of control but EE fraction of Taraxaci Herba was most effective and also hexane fraction was most effective in the combined treatment with anticancer drugs. 4. In cytotoxic effect against PLC every fractions showed the anti tumor effect in the concentrations of $10^{-5}g/ml$ above as compared with the data of control and also the combined treatment with MMC was most effective. 5. Fractions of Taraxaci Herba showed the most antitumor effect against Hep 3B and also the combined treatment with MMC was most effective. From the above result it was concluded that ethyl ether fraction of Taraxaci Herba was most effective fraction, every fraction showed more antitumor effect against Hep 3B and Hep G2 than PLC.

• 대한수의학회지
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• 제63권3호
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• pp.30.1-30.8
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• 2023

Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.

• 대한한의학회지
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• 제16권2호
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• pp.414-432
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• 1995

In order to prove the antitumer effect of Bupleuri Radix(BR) and Artemisiae capillaris Herba(ACH) experimently, studies were done. The antitumer effect against hepatic cancer such as Hep G2, PLC & Hep 313, and also th synergastic action was evaulatcd in the combined treatment with anticancer drugs using chiefly for liver cancer, such as mitomycin(MMC), cisplatin(CPT) and 5-fluorouracil(5-FU). The results were obtained as follows: 1. IC50 against Hep G2, Hep 3B and PLC was 15.5ug/ml, 25.4ug/ml, 31.25ug/ml in Mitomycin (MMC), 92.5ug/ml, 50.2ug/ml, 62.5ug/ml in cisplatin(CPT) and 125ug/ml in 5-fluouracil(5- FU) respectively. 2. The antitumor effect was shown in the all concentrations of ACH, BR and below 55%-Cytotoxic effect against Hep G2 as compared with the date of control was shown in the concentration of $10^{-4}g/ml$ above of BR but not in ACH and also BR and ACHI revealed the synergistic effect with MMC. 3. The antitumor effect was shown in the concentration of $10^{-5}g/ml$ above of ACH, BR and below 55%-Cytotoxic effect against Hep 3B as compared with the data of control was shown in the concentration of $10^{-5}g/ml$ above of ACH but not in BH and also BR & ACH revealed the svnergistic effect with MMC. 4. The antitumor effect was shown in the all concentrations of ACH, BR and 55%-Cytotoxic effect against PLC as compared with the data of control was shown in the concentration of $10^{-5}g/ml$ above of ACH but not in BR and also ACH revealed the synergistic effect with MMC. From the above results it was concluded that Artemisiae capillaris had antitumor effect against PLC, Hep 3B, Bupleuri Radix against Hep G2 and also MMC showed the most synergistic effect in the anticancer drugs.

• Journal of Korean Neurosurgical Society
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• 제42권5호
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• pp.392-399
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• 2007

Objective : Arsenic trioxide ($As_2O_3$) has been used as an anticancer agent in traditional Chinese medicine for thousand years and berberine is an isoquinoline alkaloid present that has indicated significant antimicrobial activity. We have examined the combined anticancer effects of $As_2O_3$ and berberine against the human neuroblastoma (HNB) SH-SY5Y cells in vitro, and to elucidate underlying molecular mechanism. Methods : HNB SH-SY5Y cells were treated with $2\;{\mu}M\;As_2O_3$ and $75\;{\mu}g/ml$ berberine, and their survival, cell death mechanism as well as synergistic cytotoxic effects were estimated by using MTT assay, DAPI staining, agarose gel electrophoresis, flow cytometric analysis, and western blot analysis. Results : The combined treatment of two drugs also markedly decreased cell viability. The cytotoxic effects of two drugs were revealed as apoptosis characterized by chromatin condensation, DNA fragmentation, and the loss of mitochondrial membrane potential. The apoptotic cytotoxicity was accompanied by activation of caspase-3 protease as well as decreased the expression of Bcl-2, Bid, and Bcl-x/L. In addition, the cells treated with combination of two drugs also showed significantly increased intracellular reactive oxygen species levels and lipid peroxidation compared to cells $As_2O_3$or berberine only. Conclusion : Combined treatment of $As_2O_3$ with berberine induced activation of apoptotic signaling pathways in HNB SH-SY5Y cells. These results suggest that the possibility of the combined treatment of two chemotherapeutic agents with low concentration improving cytotoxic effect for cancer cells with minimal side effects.

• 생약학회지
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• 제23권4호
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• pp.248-258
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• 1992

The studies were conducted to investigate the combined effects of several combined preparation of crude drugs and mitomycin C(MMC). The combined effects on the proliferation of HepG2, A549, KHOS-Np, A431 and HeLa cells were estimated by MTT colorimetric assays. Sa Kunja Tang(SKT), Boyang Hwanoh Tang(BHT) and Hyulbu Choogo Tang(HCT) inhibited the proliferation of A549 and HeLa cell. The inhibitory action of MMC was increased by the combined treatment of SKT and MMC, and Sa Mul Tang(SMT) and MMC, respectively. When the mice were treated by MMC, the number of leukocyte was decreased significantly at the 3rd day, but recovered at the 7th day. In the groups of MMC treated with SKT or HCT, the number of leukocyte was increased significantly that the group of MMC treated only at the 1st and 3rd day. The combined treatment of SKT, SMT, BHT, HCT and MMC retained the spleen weight of mice at the level of normal mice, but decreased the thymus weight of mice. The combined treatment of SKT, SMT, BHT, HCT and MMC increased the number of PFC significantly than the MMC treated group. The combined treatment of SKT, SMT, BHT, HCT and MMC increased the T cell proliferation significantly thant the MMC treated group.

• Tuberculosis and Respiratory Diseases
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• 제44권3호
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• pp.525-533
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• 1997

연구배경 : 수술적 절제가 불가능한 폐암환자에서 복합화학요법의 역할이 최근 증대되고 있으나 아직 가장 이상적인 복합화학요법은 확립되지 않고 있다. 두 종류 이상의 항암제를 복합투여시 약제간의 상호작용에 의해 항암효과의 상승 혹은 억제를 보일 수 있으나 이를 예측하기가 어려웠다. 본 연구에서는 MTT 검사를 이용하여 두 약제를 여러 농도에서 복합투여후 살해능의 변화를 관찰하였다. 방 법 : 사람의 폐선암세포인 PC-14를 이용하여 cisplatin, mitomycin C, adriamycin 및 etoposide를 여러 농도에서 단독 또는 두 약제를 복합투여하여 항암효과의 변화를 MTT 검사로 측정하고 두 약제 복합투여시의 상호 작용의 결과를 이원배치법을 이용한 Anova분석을 이용하여 측정하였다. 결 과 : 위의 네종류의 약제는 단독투여시 농도에 비례하는 암세포살해능을 보였고 두 약제를 복합투여시 모든 조합에서 암세포살해능의 상승효과를 보였으며 특히 mitomycin C 와 cisplatin 및 adriamycin과 cisplatin을 복합투여시 상승효과가 강하게 나타났다. 결 론 : 위의 결과로 비소세포폐암의 복합화학요법시 mitomycin C와 cisplatin 혹은 adriamycin과 cisplatin을 같이 사용할 경우 항암효과의 극대화를 얻을 수 있으리라 기대된다. 나아가 이번 연구의 디자인은 복합항암화학요법을 필요로 하는 모든 종류의 암에 적용되어 최대항암효과를 얻을 수 있는 약제선정에 도움의 될 수 있으리라 생각된다.

• 생약학회지
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• 제25권2호
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• pp.144-152
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• 1994

The combined effects of Ulmi Cortex and some anti-cancer drugs on the proliferation of HeLa cells, Hep G2 cells and S 180 cells were estimated by MTT calorimetric assay. The n-BuOH fraction(UBF) of Ulmi Cortex inhibited the proliferation of HeLa cell at $10^{-3}\;g/ml$, Hep G2 cell at $10^{-5}\;g/ml$ and S 180 cell at $10^{-3}\;g/ml$. The inhibitory effects of mitomycin C(MMC), cisplatin(CPT) and 5-fluorouracil (5-FU), respectively, on Hep G2 cell was increased by the UBF. The UBF did not influence the proliferation of Balb/c 3T3 cells at concentrations of $10^{-6}$ to $10^{-4}\;g/ml$, but increased the proliferation of T cells at concentrations of $10^{-5}$ to $10^{-4}\;g/ml$. The UBF did not influence the number of leukocyte, and on the thymus weight of mice. The UBF increased the number of total-peritoreal cells of mice. In conclusion, the results suggest that the UBF have anti-cancer activity without the side effect, such as leukopenia and immunosuppresion, and increase the inhibitory activity of the anti-cancer drugs on Hep G2 cells.

• Bulletin of the Korean Chemical Society
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• 제29권7호
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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.

• 대한수의학회지
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• 제33권4호
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• pp.701-710
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• 1993

The pine needles, Pinus densiflow Sieb. et Zucc., which is a feed for goats showing a low incidence rate of cancer were evaluated to confirm the potent anticancer effects, with or without several conventional anticancer drugs. The pine needles collected from Mt. Buk-Han located near Seoul were extracted with 95% methanol and methand and concentrated. From the methanol extract, SOM-A, was extracted dichlormethane and SOM-B was extracted with ethyl acetate. SOM-C was extracted with distilled water. These extracts were tested for their antitumor activities in vitro and in vivo. Among them, SOM-A and SOM-C exhibited potent antitumor activities described as belows. 1. The cytotoxic effects of SOM-A and SOM-C were examined against in vitro cultured murine and humman tumor cells. SOM-A showed strong cytotoxicity against human tumor cell lines and SOM-C showed strong cytotoxicity against murine tumor cell lines tested. 2. The antitumor effects of SOM-A and SOM-C were examined against P388 and L1210 of mouse ascitic tumors. The highest mean survival time(MST) ration was 151%(P388) for SOM-C(90mg/kg). 3. To compare the antitumor effects of SOM-A, SOM-B, and SOM-C against solid tumors, S-180 and Ehrlich carcinoma were implanted subcutaneously to mice on Day O. The drugs were given intraperitoneally to mice once a day on Days 1-20, and the tumor weights were measured on Day 21. SOM-A showed inhibition of tumor growth more than 50% in the experiment on S-180 and Ehrlich, and SOM-C also markedly inhibited tumor growth. However, SOM-B had no effect. 4. SOM-C combined with ${\alpha}$-interferon and SOM-C combined with Mitomycin-C enhanced the antitumor activities against murine ascitic tumors P388 leukemia.