• Bulletin of the Korean Chemical Society
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• v.15 no.5
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• pp.364-368
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• 1994

Growth inhibition potency of the anthraquinones, anthraquinone-1,5-disulfonic acid and carminic acid, for Sarcoma 180 and L1210 leukemia cells in vivo and in vitro, was induced by the divalent transition metal ion, $Cu^{2+}$. On the other hand spectroscopic titration data show that the anthraquinone drugs form $Cu2^+$ chelate complexes (carminic acid : $Cu^{2+}$ = 1 : 6; anthraquinone-1,5-disulfonic acid : $Cu^{2+}$ = 1 : 3). Furthermore the $Cu^{2+}$-drug complexes associate with DNA to form the $Cu^{2+}$-anthraquinone-DNA ternary complexes. The formation of the complexes was further supported by the $H_2O_2-dependent$ DNA degradation, which can be inhibited by ethidium bromide, caused by the $Cu^{2+}$-drug complexes. It is likely that the $Cu^{2+}$-mediated cytotoxicity of the anthraquinone drugs is related with the $Cu^{2+}-mediated$ binding of the anthraquinone drugs to DNA and DNA degradation.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.71-87
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• 1998

Even though appropriate immune response is necessary for the survival of the individual, excessive or insufficient immune Response might cause autoimmune or allergic disease. So the immune response must be controlled to the degree that is beneficial for the well being of the individual. This study was undertaken to know the effects of Gunleetang Gagambang on the immune system of the mouse. Gunleetang Gagambang has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carried out to evaluate the possible therapeutic or antitumoral effects of Gunleetang Gagambang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene(MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S180 cells). Treatment of the Gunleetang Gagambang on water-extract(dailly 1mg/mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Gunleetang Gagambang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice(TBM). Gunleetang Gagambang on also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurrence-frequency and their size. and some developed tumors were regressed by the continuous treatment of Gunleetang Gagambang extract into TBM. In vitro, treatment of Gunleetang Gagambang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Gunleetang Gagambang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Gunleetang Gagambang administration to mice enhanced NK cells activities. These results demonstrated that Gunleetang Gagambang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Gunleetang Gagambang might be chiefly due to nonspecitie enhancement of NK cell activities and cell-mediated immune responses.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.859-865
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• 2006

With an approach to study the anti-tumor effects and mechanism of selenium compound, we investigated the anti-tumor activity and mechanism of $Na_5SeV_5O_{18}{\cdot}3H_2O$ (NaSeVO) in K562 cells. The results showed that $0.625{\sim}20\;mg/L$ NaSeVO could significantly inhibit the proliferation of K562 cells in vitro in a time- and concentration-dependent manner as determined by microculture tetrazolium (MTT) assay, the IC50 values were 14.41 (4.45-46.60) and 3.45 (2.29-5.22) mg/L after 48 hand 72 h treatment with NaSeVO respectively. In vivo experiments demonstrated that i.p. administration of 5, 10 mg/kg NaSeVO exhibited an significant inhibitory effect on the growth of transplantation tumor sarcoma 180 (S180) and hepatoma 22 (H22) in mice, with inhibition rate 26.8% and 58.4% on S180 and 31.3% and 47.4% on H22, respectively. Cell cycle studies indicated that the proportion of G0/G1 phase was increased at 2.5 mg/L while decreased at 10 mg/L after treatment for 24, 48 h. Whereas S phase was decreased at 2.5-5 mg/L and markedly increased at 10 mg/L after treatment for 48 h. After treatment for 24 h, 10 mg/L NaSeVO also markedly increased S and G2/M phases. Take together, the result clearly showed that NaSeVO markedly increased S and G2/M phases at 10 mg/L. The study of immunocytochemistry showed that the expression bcl-2 is significantly inhibited by 10 mg/L NaSeVO, and bax increased. Morphology observation also revealed typical apoptotic features. NaSeVO also significantly caused the accumulation of $Ca^{2+}$ and $Mg^{2+}$, reactive oxygen species (ROS) and the reduction of pH value and mitochondrial membrane potential in K562 cells as compared with control by confocal laser scanning microscope. These results suggest that NaSeVO has anti-tumor effects and its mechanism is attributed partially to apoptosis induced by the elevation of intracellular $Ca^{2+}$, $Mg^{2+}$ and ROS concentration, and a reduction of pH value and mitochondria membrane potential (MMP).

• Journal of Ginseng Research
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• v.17 no.1
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• pp.52-60
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• 1993

Panax ginseng has been extensively used in the traditional oriental medicine as a restorative, tonic and Prophylactic agent. Recently, several reports regarding to anticancer effects of Panax ginseng has accumulated. These studies emphasized the fact that the anticancer activities might be due to a glycoside group called ginsenoside or pan.u saponin which has a water soluble characteristic. However, the authors and collaborates demonstrated that a highly lipid soluble component in extract of Panax ginseng roots contains a considerable cytotoxic activities against marine leukemic cells (L1210, P388) and human censer cells (HRT-18, HT-29, HCT48). This study was devised to observe the cytotoxic activities of Petroleum-ether extract of Panax giuseng roots (crude GBD and its Partially Purified fraction from silicic acid column chromatography (7 : 3 GX) against sarcoma-180 (5-180) and Walker carcinosar- coma 256 (Walker 256) in vivo, and murine leukemic Lymphocytes (L1210) and human rectal cancer cells (HRT-18) and human colon cancer cells (HT-29 and HCT48) in vitro. Each cell-line was cultured in medium containing serial concentration of the crude GX or 7 : 3 GX in vitro. A highly lipid soluble compound in the extract of Panax ginseng root was cytocidal to murine leukemic cells and human colon and rectal cancer cells in vitro. In the meantime, ginseng saponin derivatives did not have cytotoxic effects at its corresponding concentration. The growth rates of the cancer cells in medium containing ginseng extracts were inhibited gradually to a significant degree roughly in proportion to the increase of the extract concentration. The cytotoxic activity of 7 : 3 GX was about 3 times more potent than that of crude GX, one unit of cytotoxic activity against L1210 cells being equivalent to 2.54 Ug and 058 Ug for the crude GX and 7 : 3 GX, respectively. The Ri value of the active compound on silica- gel thin layer chromatography with petroleum-ether/ethyl ether/acetic acid mixture (90 : 10 : 1, v/v/v) as a developing so lvent was 053. While, the Panaxydol and Panaxynol as active compounds were purified from Petroleum-ether extract of Panax ginseng root by Drs. Ahn and Kim, and author found out that the one unit of cytotoxic activity of the Panaxydol and Panaxynol against L1210 cells being equivalent to 056 Ug and 0.3918 respectively. The survival times of mice inoculated with S-180 cells were extended about 1.5 to 2 times by the 7 : 3 GX treatment compared with their control group. The significantly decreased hemoglobin values of rats after inoculation with Walker 256 were recovered to normal range by oral administration of the crude Gt The synthetic levels of protein, DNA and RNA in human colon and rectal cancer cells were significantly diminished by treatment with the crude GX, which can explain a part of the origin of its anticancer activity.

• Journal of Oriental Physiology
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• v.14 no.2 s.20
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• pp.229-237
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• 1999

Hwanhonsan has been used for curing tumor as a Oriental medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Hwanhonsan extract against cancer, and to study some mechanisms responsible for its effect. Some kind of tumors were induced by the typical application of 3-methylcholanthrene(MCA) or by the implantation of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S180 cells) and FasII cells. Treatment of the Hwanhonsan extract(daily 1 mg/mouse, i.p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 hrs. Against squamous cell carcinoma induced by MCA, Hwanhonsan decreased. not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Hwanhonsan also significantly suppressed the development of 3LL cells and S180 cells implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Hwanhonsan extract into TBM. However, when tumor was induced by FsaII cells implantation, the growth of implanted cells in mice was delayed by the water extract of Hwanhonsan until 7 days and then rapid growth ensued. In vitro treatment of Hwanhonsan extract had no inhibitory effect on the tumor induced by some kind of cell lines such as A431 cells strain but it significantly inhibited the proliferation of 3LL cells, S180 cells. These results suggested that Hwanhonsan extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells.

• Journal of Life Science
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• v.23 no.11
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• pp.1388-1396
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• 2013

This study used an S-180 cell-injected mouse model to evaluate the antitumor effects of the acute and subacute toxicity of Keumsa (Phellinus linteus) extract intravenously administrated in ICR mice. When administered intravenously (31.3-250 mg/kg body weight), Keumsa (Phellinus linteus) extract significantly inhibited the growth of the solid tumor cell. The antitumor activity of Keumsa (Phellinus linteus) extract increased in a dose-dependent manner. The highest dose (250 mg/kg body weight) was highly effective, reducing tumor formation by 42.7% compared with the control group. In the acute toxicity test, $LD_{50}$ of the Keumsa (Phellinus linteus) extract showed 632.84 mg/kg (♂) and 814.48 mg/kg (♀) after intravenous administration. In addition, liver and spleen weight were increased in a dose-dependent manner. In the subacute toxicity test, the mice were intravenously administered over the course of 28 days. The $LD_{50}$ of the Keumsa (Phellinus linteus) extract showed 355.41 mg/kg (♂) and 383.53 mg/kg (♀) after intravenous administration. The liver and spleen weight also increased in a dose-dependent manner. In the case of the group that received more than 125 mg/kg of intravenous administration, exercise capacity, such as jumping ability and agility, were significantly increased. These results suggest that Keumsa (Phellinus linteus) extract can be regarded as a potent enhancer of the innate immune response, and it can be considered as a new natural product with low toxicity that may be used as a candidate for antitumor action.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.107-113
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• 1992

Increasing frequency of skin cancer, mycosis fungoides, Kaposi's sarcoma etc, it need to treatment dose planning for total skin electron beam (TSEB) therapy. Appropriate treatment planning for TSEB therapy is needed to give homogeneous dose distribution throughout the entire skin surface. The energy of 6 MeV electron from the 18 MeV medical linear accelerator was adapted for superficial total skin electron beam therapy. The energy of the electron beam was reduced to 4.2 MeV by a $0.5\;cm\times90\;cm{\times}180\;cm$ acryl screen placed in a feet front of the patient. Six dual field beam was adapted for total skin irradiation to encompass the entire body surface from head to toe simultaneously. The patients were treated behind the acryl screen plate acted as a beam scatterer and contained a parallel-plate shallow ion chamber for dosimetry and beam monitoring. During treatment, the patient was placed in six different positions due to be homogeneous dose distribution for whole skin around the body. One treatment session delivered 400 cGy to the entire skin surface and patients were treated twice a week for eight consecutive weeks, which is equivalent to TDF value 57. instrumentation and techniques developed in determining the depth dose, dose distribution and bremsstrahlung dose are discussed.

• Journal of Life Science
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• v.20 no.9
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• pp.1402-1408
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• 2010

The effects of rice hull (RH) powder on the anticarcinogenic activity of submerged-liquid cultures of Agaricus blazei Murill (AB) were assessed for mouse ascites cancers induced by mouse Sarcoma S-180 (S-180) cancer cells. Optimal growth of AB mycelia in the basal liquid culture medium, containing soybean meal, was achieved by culturing at $25^{\circ}C$ for 5 days, when evaluated by $\beta$-glucan content, Brix, and mycelial weight, relative to other culture conditions. Hot-water extract (HWE) of the submergedliquid culture of AB mycelia grown at $25^{\circ}C$ for 5 days exhibited a stronger anticarcinogenic activity, relative to HWE from other culture conditions. No such effects were obtained from AB mycelial cultures by alternative temperature-controlling cultures. Both cytotoxicity for S-180 cells and anticarcinogenic potentials for mouse ascites cancer of the HWE from AB mycelia grown in the basal medium containing 1% RH powder for 5 days at $25^{\circ}C$ were significantly (p<0.05) enhanced, relative to HWE from the AB mycelia culture of the basal medium without RH powder. These results indicate that HWE of submerged-liquid culture of AB mycelia, incubated in media containing 1% RH powder at $25^{\circ}C$ for 5 days, enhanced anticarcinogenic activity against S-180 cell-induced mouse ascites cancer, and suggest that RH powder is an excellent ingredient for the improvement of the anticarcinogenic potentials of the submerged-liquid culture of mushroom mycelia.

• Molecules and Cells
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• v.23 no.1
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• pp.30-38
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• 2007

Dipyrithione (2, 2'-dithiobispyridine-1, 1'-dioxide, PTS2), a pyrithione derivate, is highly bactericidal and fungicidal. In this study we examined its apoptotic effect on HeLa cells. PTS2 induced HeLa cell death in a dose and time dependent manner. ERK1/2 and p38 were markedly activated, but little JNK1/2 activation was detected. Suppression of p38 activation by SB203580 reduced the extent of apoptosis of the HeLa cells and also prevented induction of p21, release of cytochrome c, and cleavage of caspase-3 and PARP. Inhibition of ERK1/2 with PD98059 increased apoptosis, indicating that ERK1/2 activation has an anti-apoptotic effect on PTS2-induced HeLa cell apoptosis. PTS2 also inhibited murine sarcoma 180 and hepatoma 22 tumor growth in an animal tumor model. Our findings indicate that PTS2 possesses anti-tumor activity, that caspase-3 and poly (ADP-ribose) polymerase (PARP) are involved in PTS2-induced HeLa cell apoptosis and that ERK1/2 and p38 have opposing effects on this apoptosis.

• Journal of Society of Preventive Korean Medicine
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• v.2 no.1
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• pp.193-208
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• 1998

In order to study the effects of emitted-qi therapy, Youngyeonondamtang and Jeokyeonondamtang on the mice bearing ascites cancer caused by Sarcoma 180, the author divided the mice into normal group, control group, EQ group, YO group, JO group, CTX+QE group, CTX+YO group, CTX+JO group, and treated with emitted -qi therapy and administrated Youngyeonondamtang, Jeokyeononondaintang and Cyclophosphamide (CTX). After collecting blood from the mice, measured the values of Prothrombin Time(PT), Partial Thromboplastin Time(PTT), Fibrinogen, White Blood Cell(WBC) and Platelet. The results were as follows, 1. PT was not showed any significant change in ever)r group, being compared with the control group. 2. H increased significantly in YO group, being compared with the control group. 3. Fibrinogen decreased significantly in EQ group, YO group, CTX+EQ group, CTX+YO group, CTX+JO group, being compared with the control group. 4. WBC increased significantly in CTX+EQ group, CTX+YO group, CTX+JO group, being compared with the CTX group. 5. Platelet decreased significantly in every group, being compared with the control group. These results suggest that emitted-qi therapy, Youngyeonondamtang and Jeokyeonondamtang had the effects that could heal the hematopoiesis system in the mice bearing ascites cancer, and especially had the better effects in the case that hematopoiesis system has been impaired by CTX.