• Title/Summary/Keyword: antitumor cytotoxicity

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Effect of Selected Persimmon Leaf Components against Sarcoma 180 Induced Tumor in Mice (생쥐 육종에 대한 감잎 성분의 암 성장 억제효과)

  • Kim, Byeong-Gee;Rhew, Tae-Hyong;Choe, Eun-Sang;Chung, Hae-Young;Park, Kun-Young;Rhee, Sook-Hee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.22 no.3
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    • pp.334-339
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    • 1993
  • Antitumor activities of tannin extract and chloroform fraction extract from the persimmon leaves, and 2, 4-decadienal identified as an antimutagenic compound in persimmon leaves were examined in sarcoma 180 implanted tumor in mice by using both light and transmission electron microscopes. Among them, tannin extracted from the persimmon leaves delayed the progression of malignant tumor but the other two did not show any noticeable effect. The antitumorigenic activity of tannin extract might not come from the selective cytotoxicity against tumor cells, but might be, in an anaerobic environment, from the inhibitory action against oncogenic protein synthesis or from the proteolysis of the preformed oncogenic proteins by autophagocytic granules. therefore, the tannin from persimmon leaves might protect cells from fast progression of malignant tumorigensis.

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Preclinical Activity of Lobaplatin as a Single Agent and in Combination with Taxanes for Ovarian Carcinoma Cells

  • Sun, Xu;Lou, Li-Guang;Sui, Dong-Hu;Wu, Xiao-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9939-9943
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    • 2014
  • Lobaplatin, one of the third - generation platinum compounds, has shown encouraging anticancer activity in a variety of tumor types. However, the efficacy of lobaplatin in ovarian cancer has not been systemically evaluated. In this study, lobaplatin as a single agent and in combination with taxanes was investigated in - vitro and in an in vitro model of ovarian carcinoma. Using the sulforhodamine B (SRB) assay, the cytotoxic effects of lobaplatin alone and in combination with taxanes were compared with cisplatin and carboplatin in seven ovarian cancer cell lines. In addition, in - vitro antitumor activities were evaluated with cisplatin - sensitive and cisplatin - resistant human ovarian cancer xenografts in nude mice. The cytotoxicity of lobaplatin was similar to or higher than that of cisplatin and carboplatin, with $IC_{50}$ values from 0.9 to $13.8{\mu}mol/L$ in a variety of ovarian cancer cells. The combination of lobaplatin with docetaxel yielded enhanced cytotoxic activity in vitro. In addition, in platinum - sensitive ovarian cancer xenografts, lobaplatin alone showed similar antitumor activity to cisplatin and carboplatin. Furthermore, lobaplatin alone or in combination with docetaxel exhibited significant activity in platinum - resistant ovarian cancer xenografts. These results indicate that the use of lobaplatin alone or in combination with docetaxel might be a rational and novel therapeutic strategy for ovarian cancer. Further clinical development of lobaplatin is clearly warranted.

Isolation and Characterization of Antitumor Agents from Xanthium strumarium L. (한국산 도꼬마리로부터 항암물질의 분리 및 특성)

  • 김현수;이인선;여수환;성림식;유대식
    • KSBB Journal
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    • v.18 no.4
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    • pp.324-328
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    • 2003
  • In a mutagenicity test using the Salmonella typhimurium TA98 and TA100, the Xanthium strumarium L. extracts had not a mutagenicity. The extracts were assayed that antioxidative effect using a colony formation assay. The extracts showed protective effects against the cytotoxicity of H$_2$O$_2$ and increased the immunity induced by TNF and IL-1${\beta}$. The modulating effect of Xanthium strumarium L. extract on the induction of carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidin (MNNG), was investigated in Wistar rats. The GSH content was found to be reduced by MNNG treatment, but increased on adding extract. In addition the Xanthium strumarium L. extract increased p53 expression versus MNNG alone.

The Anticancer Effects and Immune Response on the Metastatic Lung Cancer by Wanpae-tang (완폐탕의 실험적 폐전이암에 대한 항암 및 면역효과에 관한 연구)

  • Lee Seon Goo;Lee Dong Joo;Yoon Keun Chan;Ha Jee Yong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.3
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    • pp.711-718
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    • 2003
  • Wanpae-tang is suggested to have antitumor activity on lung cancer. This study was performed to investigate antitumor, immune response, and apoptotic effects by Wanpae-tang in the cancer cell lines and C57BL/6 mice. Experimental studies were progressed through the anticancer activities such as, survival time, cell cytotoxicity, natural killer cell activity, productivity of interleukins and apoptotio effects. The results were summarized as follows: 1. Median survival time of Wanpae-tang treated group was prolonged to 4.1%, as compared with control group, but was not significant. 2. On the MTT assay, half-maximal inhibitory concentration(IC50) of Wanpae-tang was 15.00 ㎎/㎖ in HeLa cell, and 4.158 ㎎/㎖ in HRT-18 cell. 3. Natural killer cell activity in Wanpae-tang treated group was decreased in case of 100:1 and 10:1 effect cell/target cell ratio. 4. Production of interleukin-2, 4, 12 in Wanpae-tang treated group were significantly increased. 5. On the studies of Wanpae-tang induced apoptosis, a DNA fragmentation patterns were not appeared.

In Vivo Toxicity and Anti-Tumor Activity of Korean Mistletoe Extracts (한국산 겨우살이 추출물의 in vivo 독성 및 항종양 효과)

  • Yoon, Taek-Joon;Park, Sung-Min;Yang, Seung-Hoon;Jung, Hoe-Yune;Lee, An-Na;Yoo, Yung-Choon;Kang, Tae-Bong;Kim, Jong-Bae
    • Korean Journal of Pharmacognosy
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    • v.40 no.3
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    • pp.205-212
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    • 2009
  • Antitumor activity of Korean mistletoe extract (KM-110) and European commercial mistletoe preparation (Helixor) was investigated. KM-110 showed the cytotoxic effect that it is high for various tumor cell lines and normal splenocytes in comparison with Helixor. Administration of two mistletoe extracts ($100{\mu}g$) to mice did not show any significant changes on the level of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvate transaminase (GTP), blood creatinine (CRE) and blood urea nitrogen (BUN) in sera. The culture supernatant of macrophages stimulated with KM-110 inhibited effectively tumor growth whereas Helixor had little effect. Administration of KM-110 or Helixor resulted in a effective inhibition of lung metastasis after the i.v. inoculation of colon 26-M3.1 lung carcinoma, B16-BL6 melanoma and L5178Y-ML25 lymphomas. In all cases, the mice treated with KM-110 showed more effective anti-tumor metastatic activity than the mice of Helixor. These results suggest that Korean mistletoe extracts, KM-110 might be used as an alternative methods having antitumor activity like European mistletoe preparation, Helixor.

Constituents and the Antitumor Principle of Allium victoriallis var. platyphyllum

  • Lee, Kyung-Tae;Choi, Jung-Hye;Kim, Dong-Hyun;Son, Kun-Ho;Kim, Won-Bae;Kwon, Sang-Hyuk;Park, Hee-Juhn
    • Archives of Pharmacal Research
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    • v.24 no.1
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    • pp.44-50
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    • 2001
  • To search for cytotoxic components from Allium victoriallis , MTT assays on each extract and an isolated component, gitogenin 3-O-lycotetroside, were performed against cancer cell lines. Cytotoxicities of most extract were shown to be comparatively weak, though $IC_50$ values of $CHCl_3$fraction was found to be <31.3-368.4 $\mu\textrm{g}/ml$. From the incubated methanol extract at $36^{\circ}C, eleven kinds of organosulfuric flavours were predictable by CG-MS performance. The most abundant peak was revealed to be 2-vinyl-4H-1,3-dithiin(1) by its mass spectrum. Further, this extract showed significant cytotoxicities toward cancer cell lies. Silica gel column chromatography of the n-butanol fraction led to the isolation of gitogenin 3-O-lycotetroside (3) along with astragalin (4) and kaempferol 3, 4'-di-O-$\beta$-D-glycoside (5). This steroidal saponin exhibited significant cytotoxic activities ($IC_50$, 6.51-36.5 $\mu\textrm{g}/ml$) over several cancer cell lines. When compound 3 was incubated for 24 h with human intestinal bacteria, a major metabolite was produced and then isolated by silica gel column chromatography. By examining parent and prominent ion peak in FAB-MS spectrum of the metabolite, the structure was speculated not to be any of prosapogenins of 3, suggesting that spiroketal ring were labile to the bacterial reaction. These suggest that disulfides produced secondarily are the antitumor principles.

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Antineoplastic Natural Products and the Analogues(IX). A Review of the Series

  • Ahn, Byung-Zun;Kim, Shin-Il;Ryu, Sung-Ho;Kang, Kyu-Sang;Lee, You-Hui
    • Korean Journal of Pharmacognosy
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    • v.17 no.2
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    • pp.168-177
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    • 1986
  • Bioassay-directed isolation has yielded some cytotoxic substances against L1210 cell from the Korean traditional medicine. These include 5,2'-dihydroxy-6,7,8,6'-teramethoxyflavone $(IV,\;scutellaria\;root,\;ED_{50}\;=\;1.7\;{mu}g/ml)$, 7-geranyloxycoumarin $(XXXII,\;poncirus\;fruit,\;10.2\;{mu}g/ml) $and panaxydol $(I,\;white\;ginseng,\;0.03\;{mu}g/ml)$. IV, XXXII and their derivatives were synthesized in the purpose of in vivo tests and for observation of structure-activity relations. Among the flavone derivatives, 5,2',6'-trihydroxy-6,7,8-trimethoxy flavone (XVIII), 5-hydroxy-6,7,8-trimethoxy-6'-benzyloxyflavone (XVII) and 5,8-dihydroxy-6,7-dimethoxyflavone (X) showed the cytotoxicity which has no correlation to the flavone structures. Of the coumarins synthesized, 7,8-dihydroxycoumarin (XXVI), 6-7-dihydroxycoumarin (XXIX) and 6-hydroxy-5,7-dimethoxycoumarin (XXXI) showed considerable activities. Acetylated XXXI has moderate activity $(ED_{50}=17.2\;{mu}g/ml)$. Monobydroxycoumarins or their methyl and allyl ether were inactive. IV inhibits the growth of the solid form of S-180 by 70% at 40 mg/kg and shows T/C of 166% on the ascitic S-180 at 40 mg/kg. It strongly inhibits the activity of the membrane bounded ATPase from L1210 cell. The most cytotoxic fraction of the antitumor materials studied is the one from the trichosanthes root showing $ED_{50}=0. 0003\;{mu}g/ml$ against L1210 cell. This fraction, obtained from ethyl acetate extract, showed T/C of 130 and 135%, on ICR mice bearing S-180 and $BDF_1$ mice bearing L1210 at 10 mg/kg and 7.5 mg/kg, respectively.

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Investigation of Antitumor Effects of Sorafenib and Lapatinib Alone and in Combination on MCF-7 Breast Cancer Cells

  • Kacan, Turgut;Altun, Ahmet;Altun, Gulsah Gultekin;Kacan, Selen Baloglu;Sarac, Bulent;Seker, Mehmet Metin;Bahceci, Aykut;Babacan, Nalan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3185-3189
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    • 2014
  • Background: Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. Materials and Methods: Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and $6.25{\mu}M$ concentrations of sorafenib and 200, 100, 50 and $25{\mu}M$ concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and $IC_{50}$ values are calculated according to the absorbance data Results: Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an $IC_{50}$ value of $32.0{\mu}M$; in contrast with lapatinib the $IC_{50}$ was $136.6{\mu}M$. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells. Conclusions: Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer.

Antitumor Activity of Lentivirus-mediated Interleukin -12 Gene Modified Dendritic Cells in Human Lung Cancer in Vitro

  • Ali, Hassan Abdellah Ahmed;Di, Jun;Mei, Wu;Zhang, Yu-Cheng;Li, Yi;Du, Zhen-Wu;Zhang, Gui-Zhen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.611-616
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    • 2014
  • Objectives: Dendritic cell (DC)-based tumor immunotherapy needs an immunogenic tumor associated antigen (TAA) and an effective approach for its presentation to lymphocytes. In this study we explored whether transduction of DCs with lentiviruses (LVs) expressing the human interleukin-12 gene could stimulate antigen-specific cytotoxic T cells (CTLs) against human lung cancer cells in vitro. Methods: Peripheral blood monocyte-derived DCs were transduced with a lentiviral vector encoding human IL-12 gene (LV-12). The anticipated target of the human IL-12 gene was detected by RT-PCR. The concentration of IL-12 in the culture supernatant of DCs was measured by ELISA.Transduction efficiencies and CD83 phenotypes of DCs were assessed by flow cytometry. DCs were pulsed with tumor antigen of lung cancer cells (DC+Ag) and transduced with LV-12 (DC-LV-12+Ag). Stimulation of T lymphocyte proliferation by DCs and activation of cytotoxic T-lymphocytes (CTL) stimulated by LV-12 transduced DCs pulsed with tumor antigen against A549 lung cancer cells were assessed with methyl thiazolyltetrazolium (MTT). Results: A recombinant lentivirus expressing the IL-12 gene was successfully constructed. DC transduced with LV-12 produced higher levels of IL-12 and expressed higher levels of CD83 than non-transduced. The DC modified by interleukin -12 gene and pulsed with tumor antigen demonstrated good stimulation of lymphocyte proliferation, induction of antigen-specific cytotoxic T lymphocytes and antitumor effects. Conclusions: Dendritic cells transduced with a lentivirus-mediated interleukin-12 gene have an enhanced ability to kill lung cancer cells through promoting T lymphocyte proliferation and cytotoxicity.

Studies on Development of New Basidiomycetes by Protoplast Fusion and Nuclear Transfer II - The Effects of the Components of the Protoplast Fusants on Mouse Immune Cells - (원형질체 융합 및 핵전이에 의한 새로운 담자균류의 개발에 관한 연구(II) - 융합균사체의 항암성분이 생쥐의 면역세포에 미치는 영향 -)

  • Moon, Chul;Kim, Chae-Kyun;Yoon, Jong-Myung;Shim, Mi-Ja;Kim, Ha-Won;Choi, Eung-Chil;Kim, Byong-Kak
    • Korean Journal of Pharmacognosy
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    • v.27 no.3
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    • pp.231-237
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    • 1996
  • The antitumor components of the protoplast fusants of Lentinula edodes and Ganoderma lucidum were examined for immunological activity to elucidate the mechanism of their antitumor activity. They did not show any direct cytotoxicity against tumor cells. But being examined for immunopotentiation activity, they increased the number of colonies in the bone marrow stem cells to 3.0 times. They also increased the activities of the acid phosphatase in activated macrophages to 2.1 times and the secretion of nitric oxide in RAW 264.7 to 2.2 times, respectively. They activated the components of the alternative complement pathway. In humoral immunity. they increased the activities of the alkaline phosphatase in differentiated B cells to 1.6 times and the number of plaque forming cells to 1.8 times, respectively. In cellular immunity, they restored the depressed response of delayed type hypersensitivity in tumor bearing mice to normal level.

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