Indonesian Journal of Cancer Chemoprevention
Articles by issue : Vol 1, No 2 (2010)
10
Articles
Cyclosporine A and FK506 as Potent Inhibitors of Streptococcus intermedius Intermedilysin-Induced NFAT-1 Activation

Susilowati, Heni ( Department of Oral Biology, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta ) , Okamura, Hirohiko ( Department of Histology and Oral Histology The University of Tokushima Graduate School, Tokushim ) , Hirota, Katsuhiko ( Department of Oral Microbiology The University of Tokushima Graduate School, Tokushim ) , Yoshida, Kaya ( Department of Histology and Oral Histology, Department of Fundamental Oral Health Science, School of Oral Health and Welfare, Institute of Health Biosciences The University of Tokushima Graduate School, Tokushim ) , Tabata, Atsushi ( Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan ) , Nagamune, Hideaki ( Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan ) , Haneji, Tatsuji ( Department of Histology and Oral Histology The University of Tokushima Graduate School, Tokushim ) , Miyake, Yoichiro ( Department of Oral Microbiology The University of Tokushima Graduate School, Tokushim )

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Research Gateway

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Abstract

Cyclosporine A (CsA) and tacrolimus (FK506), a member of calcineurin inhibitors, inhibit inflammation process as part of immune response. Nuclear activated T cells subfamily NFAT1 is a trascription factor responsible for the regulation of immune response genes. Streptococcus intermedius, an oral commensal bacterium, has been shown to strongly associate with liver abscess.  The S. intermedius strains produce intermedilysin (ILY), which is responsible for the bacterial virulence. Cyclosporine A and FK506 have been widely used to control NFAT activation in most of cell types, however the ability of CsA and FK506 to inhibit ILY-induced NFAT1 activation remains to be investigated. The aim of this study was to investigate the effect of  CsA and FK506 on NFAT1 activation caused by ILY. Human cholangiocellular cell line HuCCT1 was stimulated with various concentrations of ILY. The cell and nuclear morphological change was observed by microscopy analysis. The NFAT1 nuclear translocation that indicates its activation was detected by immunocytochemistry. The inhibitory effect of CsA and FK506 was tested after 30 min application before ILY treatment by using immunofluorescence microscope. The results showed cell and nuclear shrinkage in ILY-treated cells. The NFAT1 was translocated to the nuclei in HuCCT1 cells, and observed in dose dependent manner.  Cyclosporine A and FK506 inhibited ILY-induced NFAT1 nuclear translocation.  In conclusion, CsA and FK506 may act as potent inflammation control agents in S. intermedius ILY-infected cells.

Fatty Acids Composition of Red and Purple Pomegranate (Punica granatum L) Seed Oil

Soetjipto, Hartati ( Department of Chemistry, Faculty of Science and Mathematic Satya Wacana Christian University, Salatiga ) , Pradipta, Murda ( Department of Chemistry, Faculty of Science and Mathematic Satya Wacana Christian University, Salatiga ) , Timotius, KH ( Department of Chemistry, Faculty of Science and Mathematic Satya Wacana Christian University, Salatiga )

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Research Gateway

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Abstract

The aim of this investigation was to determine the content and composition of  fatty acid in seed oil of red and purple pomegranate (  Punica granatum L). The extraction process was performed by Soxhlet extractor with petroleum ether as solvent. The separation and identification of pomegranate seed oil was done by using GCMS. The total oil content of red and purple  pomegranate  were 128 g/kg d.w  and 103 g/kg d.w respectively. Both showed the same major fatty acids  as palmitic, stearic, oleic, linoleic and  punisic acid. Oleic acid ( 19-21% ) and linoleic acid ( 20-21% ) were found as the most  dominant fatty acids in red pomegranate, whereas purple pomegranate seed oil was dominated by oleic acid ( 41-43% ) and punicic acid  ( 0-25% ). Neutral lipid  fraction of  red and purple pomegranate seed oils was more dominantthan glycolipid and phospholipid. Neutral  lipid fraction  of red and purple pomegranate seed oil were  89 % and 91% respectively.  Glycolipid fraction  of red and purple pomegranate seed oil were 8 % and 5 % , whereas phosholipid fraction of red and purple pomegranate seed oil were 3 % and 4 %. The punicic acid content of  total lipid of  purple pomegranate seed oil ( PPSO ) (0-25% ) was higher than red pomegranate ( RPSO ) ( 9-16% ). On the contrary neutral lipid of red pomegranate showed higher punicic acid content (54-75%) than the purple pomegranate (14-55% ). Glycolipid of red pomegranate contained  punicic acid  ( 0-42%). The punicic acidcontent  of the phospholipid fraction of  red pomegranate was higher ( 0-22 % ) than the one of  purple pomegranate (0-2% ).

Combination of Solanum nigrum L. Herb Ethanolic Extract and Doxorubicin Performs Synergism on T47D Breast Cancer Cells

Anindyajati, . ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta ) , Sarmoko, . ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta ) , Putri, Dyaningtyas D. P. ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta ) , Hermawan, Adam ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta ) , Meiyanto, Edy ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta )

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Research Gateway

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Abstract

Leunca (Solanum nigrum L.) has been proven to possess  anticancer activity on some type of cancer cells. In vitro study of solamargine found in the herb showed cytotoxic effect against several breast cancer cell lines, such as T47D and MDA-MB-31. Hence, further study on its potential as a co-chemotherapeutic agent needs to be conducted, in order to overcome resistance problem commonly found in cancer  chemotherapy. This study aimed to examine the cytotoxic activity of leunca herb ethanolic extract (LEE) alone and its combination with doxorubicin. Single and combinational treatment of LEE and doxorubicin on T47D breast cancer cells were done, and their viability representing cytotoxicity were analyzed by using MTT assay to determine the IC50 value and combination index (CI) to evaluate the combinational effect.  Twenty four hours-treatment of LEE  alone gave cytotoxicity activity showing a dose-dependent manner with the IC50 of 47 µg/ml, while combinational treatment showed that 4 µg/ml LEE was found to be synergist with 4 nM doxorubicin on T47D cells, with the optimum CI value of 0.59. This result shows that Solanum nigrum L. is potential to be proposed as doxorubicin co-chemotherapeutic agent against breast cancer. Further study on its molecular mechanism needs to be conducted.

Antioxidant Activity of Garcinia cf bancana Miq

Hartati, Sri ( Research Center for Chemistry, Indonesia Institute of Sciences,   Kawasan Puspiptek Serpong Tangerang.  ) , Triyem, . ( Department of Chemistry, Indonesia University. UI- Depok ) , Cahyana, Herry ( Department of Chemistry, Indonesia University. UI- Depok )

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Research Gateway

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Abstract

Guttiferron F and essential oil were isolated from extract  n-hexane of  Garcinia cf bancana  Miq. Antioxidant activity was done by DPPH method to   n-hexane, methanol, ethyl acetate, n-butanol extracts and Guttiferron F, showed activity with IC50 24.5, 22.4, 29.2, 37.6 and 25.8 µg/mL respectively. The structure elucidation of Guttiferon F  based on spectroscopy data of IR, NMR of 1H and 13C.

Secretion of Indoleamine 2,3-Dioxygenase, an Immunomodulatory Substance, by Adipose-Derived Mesenchymal Stem Cell

Laksmitawati, Dian R ( Faculty of Pharmacy, Pancasila University, Jakarta, Indonesia ) , Sardjono, Caroline Tan ( Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia ) , Pawitan, Jeanne A. ( Faculty of Medicine University of Indonesia, Jakarta, Indonesia ) , Sadikin, Mohammad ( Faculty of Medicine University of Indonesia, Jakarta, Indonesia ) , Sandra, Ferry ( Stem Cell and Cancer Institute, Jakarta, Indonesia )

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Research Gateway

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Abstract

Lipoaspirate, a wasted by product from liposuction procedure recently has been shown to contain abundant adipose-derived-mesenchymal stem cells (MSCs). Mesenchymal stem cells (MSCs) have been studied in many research areas to regenerate many cell lineages. In addition, MSCs have immunomodulatory effect. This capability has been utilized in several clinical studies in hematopoetic stem cell and organ transplantation as a strategy to reduce the risk of Graft versus Host Disease (GvHD). It has been reported that the ‘stimulated’ MSC is able to secrete substances to suppress tissue rejection. One of the substances was known to be indoleamine 2,3-dioxygenase (IDO).  A previous study has  characterized the secretion of IDO by bone marrow-derived MSCs stimulated by an inflammatory mediator interferon gamma (IFN-γ). IDO has been detected using Western blot analysis and by High Performance Liquid Chromatography (HPLC) assay. The aim of this study was to detect the presence of IDO in AD-MSCs culture with and without INFγ stimulation. Our study showed that AD-MSC stimulated with IFN-γ significantly secreted high level of IDO as detected by Enzyme-Linked Immuno Sorbent Assay (ELISA). Despite its property as a proinflammatory mediator, IFN-γ has shown to be able to induce IDO secretion in MSC culture which suggests the immuno modulatory effect of MSC. This study clearly demonstrates the potential application of adipose-derived MSC in the immunomodulatory strategy for allogenic transplantation.  

Apoptosis and Antioxidant Activities of Catharanthus rosues [L] G.Don Extract on Breast Cancer Cell Line

Widowati, Wahyu ( Medical Research Center, Faculty of Medicine, Maranatha Christian University, Bandung ) , Mozef, Tjandrawati ( The Indonesian Institute of Sciences, Bandung ) , Risdian, Chandra ( The Indonesian Institute of Sciences, Bandung ) , Ratnawati, Hana ( Medical Research Center, Faculty of Medicine, Maranatha Christian University, Bandung ) , Tjahyani, Susy ( Medical Research Center, Faculty of Medicine, Maranatha Christian University, Bandung ) , Sandra, Ferry ( Stem Cell and Cancer Institute, Jakarta )

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
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Abstract

Tapak dara or Madagascar Periwinkle (Catharanthus roseus [L] G.Don), a natural plant, is empirically reported to have promising anticancer activity. To elucidate its mechanism, a research was conducted to investigate the possible ethanol extract of  C.  roseus in inducing apoptosis on breast cancer cell line (T47D). Antioxidant activity of C. roseus was investigated as well. Sub-G1 flowcytometric apoptotic analysis result showed that extract of C. roseus at 6.25 μg/mL induced apoptosis for 26.365%. Increasing extract concentration resulted an increasing apoptotic level as well, extract at concentration of 12.5 μg/mL induced apoptosis for 22.235%.  Meanwhile doxorubicin at concentration of 10  μg/mL induced apoptosis for 36.055%. The antioxidant activity was determined by using  in vitro assay: inhibition of  2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging  activity. Antioxidant activity of  C. roseus extract were compared to quercetin and butylated hydroxyanisol (BHA), as positive controls.  The results showed that DPPH IC50 of C. roseus extract, quercetin and BHA were 358.411 μg/mL, 19.200 μg/mL  and  94.178  μg/mL, respectively. We suggest that  C. roseus extract had a potential anticancer activity by inducing apoptosis.

Molecular Docking of Lunacridine from Lunasia amara to DNA : Its Inhibition And Interaction Study Correlated With The Cytotoxic Activity on P388 Murine Leukemia Cells

Zubair, M Sulaiman ( Faculty of Mathematics and Natural Sciences, Tadulako University, Soekarno Hatta Street, Palu, 90411, Indonesia ) , Subehan, . ( Faculty of Pharmacy, Hasanuddin University, Perintis Kemerdekaan km.10 Street, Makassar, 90245, Indonesia )

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
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Abstract

DNA Topoisomerase II inhibitors are a type of anticancer drugs. These drugs perform their biological activity either by forming a DNA-intercalator-topoisomerase II ternary complex or by inhibiting other enzymes and/or transcription factors that act on DNA. The strong interactions with DNA play a crucial role for their pharmacological properties. Lunacridine, the active principle from  Lunasia amara,  was known as DNA intercalating Topoisomerase II inhibitor. With the aims to explore the affinity and molecular interaction of lunacridine compound isolated from  Lunasia amara with DNA, molecular docking study has been carried out with DNA model using Autodock 4.0 software. Cytotoxicity test on P388 murine leukemia cells was done also using 100, 30, 10, 3 and 1  μg/ml series of lunacridine concentration. The docking result shows that Lunacridine itself could to dock intercalatively between base pairs of DNA and the possibility interaction with adenine, thymine and cytosine by dipole-dipole interaction.  The lowest predicted binding energy of lunacridine is –6,22 kcal/mol, whereas original ligand bis thiazole is -16,37 kcal/mol.  Lunacridine compound itself has less cytotoxic activity on P388 murine leukemia cells with the IC50 value of 39,52  μg/ml or 129,41  μM. The binding energy of lunacridine on DNA higher than original ligand show that the interaction of lunacridine with DNA is not stable afford the  less cytotoxic activity. However, based on the IC50 value, lunacridine could be depeloved as anticancer. 

Chemopreventive Efficacy of Ginger Extract (Zingiber officinale)

Harliansyah, . ( Department of Biochemistry, Yarsi University School of Medicine, Jakarta, Indonesia   ) , Zurinah, W.N. Wan ( Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia ) , Anum, M.Y. Yasmin ( Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia ) , Azian, M Noor ( Centre of Lipids and Engineering and Applied Research, Universiti Teknologi Malaysia )

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
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Abstract

The liver cells were cultured in the  presence of ginger extract at various concentrations (0-1 mg /ml) for 24 h and the cells viability and proliferation rate were evaluated by MTS and BrdU assays, while  apoptosis was evaluated by colorimetric determination of caspase 8 and 3 activities.  Ginger extract exhibited a dose dependent inhibition of viability and proliferation of WRL-68, HLE and HepG2 cells with IC50 of 569.69 ± 7.99 µg/ml, 389.71 ± 26.56 µg/ml and 358.71 ±  17.12 µg/ml respectively. Ginger extract induced apoptosis through activation of caspase-8 and 3 in a dose dependent pattern for all cells at concentration ranging from 0-500  μg/ml.  We found that antiproliferative effect of ginger extract could be associated with induction of apoptosis as shown by increased activities of caspase 8 and 3.The results from this study suggest that ginger extract has chemopreventive properties against hepatoma cells HepG2 and HLE by inhibiting cellular proliferation and inducing apoptosis.

Ethanolic Extract of Moringa oleifera L. Increases Sensitivity of WiDr Colon Cancer Cell Line Towards 5-Fluorouracil

Nur, Kholid Alfan ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada ) , Putri, Herwandhani ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada ) , Cahyani, Fany Mutia ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada ) , Katarina, Aulia ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada ) , Susidarti, Ratna Asmah ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada ) , Meiyanto, Edy ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada )

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
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Abstract

For more than four decades, combination chemotherapy (co-chemotherapy) has been employed as a means to increase the effectiveness of chemotherapy regiments. The aim of our research is to investigate the activity of  Moringa oleifera  L. (tanaman kelor) ethanolic extract (MEE) as a co-chemotherapy agent with 5-fluorouracil (5-FU) on WiDr colon cancer cell line. Evaluation of MEE potency as a co-chemotherapy agent with 5-FU was based on cytotoxic activity based on percent cell viability via MTT  assay, and based on apoptosis observation via the double staining method using acrydin orange – ethidium bromide (AE) as the staining reagent.Cytotoxicity evaluation of single treatment using concentrations of 5, 20, 50, 100,125, and 250 µg/ml of MEE reduced cell viability 24 hours post-treatment. 5, 50, and 250 µg/ml of MEE was chosen as the combination concentrations with 1000 µM 5-FU. MTT assay 24 hours and 48 hours post-combination treatment showed significant cell viability reduction in comparison to those of single treatments. Apoptosis observation using the double staining method shows the presence of apoptotic cells 48 hours post combination treatment. MEE is a potential co-chemotherapy agent  by increasing the sensitivity  of WiDr colon cancer cell line towards 5-FU.

QSAR Analysis of Rocaglamide Derivatives Cytotoxic Activities Using LFER Hansch Model

Firdayani, . ( Center of Pharmaceutical and Medical Technology Agency on Assessment and Application of Technology (BPPT) ) , Kusumaningrum, Susi ( Center of Pharmaceutical and Medical Technology Agency on Assessment and Application of Technology (BPPT) ) , Setyo Utomo, Doddy Irawan ( Center of Pharmaceutical and Medical Technology Agency on Assessment and Application of Technology (BPPT) ) , Wibowo, Agung Eru ( Center of Pharmaceutical and Medical Technology Agency on Assessment and Application of Technology (BPPT) ) , Chaidir, . ( Center of Pharmaceutical and Medical Technology Agency on Assessment and Application of Technology (BPPT) )

Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
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Abstract

Rocaglamide derivatives are the compounds which have featuring cyclopenta[b]tetra-hydrobenzofuran skeleton. Until now it includes more than 50 naturally occurring derivatives. They were chosen to be interesting candidates for possible therapeutic agents primarily in the field of cancer chemotherapy due to their cytotoxic activities data against various cancer cells. A quantitative structure activity relationship (QSAR) studies were done to investigate physicochemical properties of molecule which  contribute to their activities. Series of rocaglamide derivatives have been used and analyzed using linear free energy regression Hansch model for their cytotoxic activities against MONO-MAC-6 leukemia cells, RAJI lymphoma cells and MEL-JUSO melanoma cells. Results showed that the best QSAR equations were revealed involving C Log P and CMR parameters with nonlinear regression relationships in cytotoxic activities of rocaglamide derivatives against cancer cells above.