Indonesian Journal of Cancer Chemoprevention
Articles by issue : Vol 2, No 3 (2011)
10
Articles
In Vitro Antioxidant Activity of Zingiber officinale, Piper retrofractum, and Their Combinations

Wasito, Hendri ( Pharmacy Departement, Medicine and Health Sciences Faculty, Jenderal Soedirman University Jln. Dr. Soeparno, Karangwangkal, Purwokerto ) , Ekowati, Heny ( Pharmacy Departement, Medicine and Health Sciences Faculty, Jenderal Soedirman University Jln. Dr. Soeparno, Karangwangkal, Purwokerto ) , Hayati, Fitri Fauziah ( Pharmacy Departement, Medicine and Health Sciences Faculty, Jenderal Soedirman University Jln. Dr. Soeparno, Karangwangkal, Purwokerto )

Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

Many  plants  are  used  empirically  as  antioxidant.  Plants  that  are  frequently  used  in Indonesian  communities  are  Zingiber  officinale  and  Piper  retrofractum.  The  aim  of  this  research was  to  investigate  the  in  vitro  antioxidant  activity  of  single  ethanolic  extract  and  the combinations ofZ. officinale and P. retrofratum using free radical scavenging DPPH (1,1-diphenyl-2-picrylhydrazyl)  method.  Z.  officinale  and  P.  retrofratum  were  extracted  by  maceration  using 95%  ethanol  for  3  x  24  hours. Antioxidant  activity  was  evaluated  using  1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The concentration of the extract (μg/mL) that was required to scavenge 50% of free radicals (IC50)was calculatedusing the percent scavenging activities of six different  extract  concentrations.  The  results  showed  that  the  single  ethanolic  extract  of  Z. Officinalle produced the highest antioxidant activity with IC50of 56 μg/mL, while the antioxidant  activity of the single ethanolic extract of  P. retrofractum produced an IC50 of 3.445 μg/mL. The IC50 of combination of Z. officinale and P. retrofratum ethanolic extracts at concentration ratios of 1: 2, 1 : 1, and 2 : 1 were 148 μg/mL, 85 μg/mL, and 73 μg/mL.Key words: Zingiber  officinale, Piper retrfratum, Antioxidant, DPPH

Antiproliferative Effect and Apoptosis Induced in Human Cell Lines by Bruguiera gymnorhiza Barks Methanol Extract

Warsinah, . ( Department Pharmacy, Faculty of Medicine and Health Sciences, Universitas Jendral Soedirman, Purwokerto ) , Sismindari, . ( Faculty of Pharmacy, Gadjah Mada Univesity, Yogyakarta ) , Susidarti, Ratna Asmah ( Faculty of Pharmacy, Gadjah Mada Univesity, Yogyakarta )

Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

The Antiproliferative effects of methanol extract from Bruguiera gymnorhiza (B. gymnorhiza) barks were tested in vitro against three human cell lines: Hela, Raji and Myeloma cells. The extract was found to have antiproliferative effects against Hela, Raji and Myeloma cells with an IC50 value of 133, 504 and 384 µg/mL, respectively. The antiproliferative test was then performed on Hela, Raji,  and  Myeloma  cells.  Cytotoxicity  assay  of  the  extract  was  then  determined  using  MTT method.  There  were  some  indications  of  apoptosis,  such  DNA  fragmentation,  as  assessed  by acrydine orange- ethidium bromide staining. These results indicate that extract from B. gymnorhiza barks can induce apoptosis in human cell lines.Key words: Antiproliferative, Apoptosis, B. gymnorhiza

MCF-7 Resistant Doxorubicin are Characterized by Lamelapodia, Strong Adhesion on Substrate and P-gp Overexpression

Putri, Dyaningtyas Dewi P. ( 1. Cancer Chemoprevention Research Center, Faculty of Pharmacy, UGM 2. Graduate Student of Faculty Pharmacy UGM ) , Sarmoko, . ( 1. Cancer Chemoprevention Research Center, Faculty of Pharmacy, UGM 2. Graduate Student of Faculty Pharmacy UGM ) , Febriansah, Rifki ( 1. Cancer Chemoprevention Research Center, Faculty of Pharmacy, UGM 2. Graduate Student of Faculty Pharmacy UGM ) , Puspitasari, Endah ( 1. Cancer Chemoprevention Research Center, Faculty of Pharmacy, UGM 2. Graduate Student of Faculty Pharmacy UGM ) , Ismiyati, Nur ( 1. Cancer Chemoprevention Research Center, Faculty of Pharmacy, UGM 2. Graduate Student of Faculty Pharmacy UGM ) , Fitriasari, Aditya ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, UGM )

Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

The  prognosis  of  breast  cancer  patients  is  closely  associated  with  the  response  of tumor  cells  to  chemotherapy  agent.  Doxorubicin  is  one  of  the  primary  chemotherapeutic agents  used  for  the  treatment  of  breast  cancer.  Resistance  to  chemotherapy  is  believed  to cause  treatment  failure  in  cancer  patients.  Furthermore,  long  time  exposure  to chemotherapeutic  agent  induces  cancer  cells  resistance.  MCF-7  sensitive  cells  used  as chemoresistance  model  have  overexpression  P-gp  (P-glycoprotein).  Chemoresistance  was established by treating MCF-7 cells with 0.5 µg/ml doxorubicin-contained medium for a week. 50% inhibiting concentration (IC50) doxorubicin on MCF-7 cells/DOX were determined using MTT assay. Western blot assay and immunocytochemistry assay was performed to determine the expression of P-gp. Morphological of MCF-7 cell/DOX was changing to become larger and have  lamellapodia.  IC50  value  of  doxorubicin  was  700  nM  on  MCF-7/DOX  and  400  nM  on sensitive MCF-7 cells. The MCF-7/DOX sensitivity to doxorubicin was decreased, shown by 1.5  fold  higher  IC50  of  doxorubicin  on  MCF-7/DOX  compared  to  MCF-7  sensitive  cells. Treatment doxorubicin to sensitive MCF-7 cells leads to the increasing P-gp expression. The P-gp  level  expression  has  strong  correlation  with  the  low  sensitivity  of  MCF-7/DOX  to doxorubicin.Key words: doxorubicin, resistance cells, sensitive MCF-7 cell

Anticancer Evaluation of Plants from Indonesian Tropical Rain Forests

Abbas, Jamilah ( Research Centre for Chemistry, Indonesian Institute of Sciences PUSPIPTEK. Serpong. 15314. Indonesia )

Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

The  anticancer  activities  of  medicinal  plants  from Indonesia’s tropical rainforests were investigated  against  Hela  cell  line.  Maytenfoliol  from  leaves  of  Calophyllumtetrapterum  3-epibetulinic  acid  from  stem  bark  of    C.  tomentosum Wight  and  D.A-friedo-oleanan-3-on  from stem bark of C. moonii showed anticancer activity. The compound 3-epibetulinic acid showed the more potent anticancer activity than maytenfoliol  and D.A-friedo-oleanan-3- with thean IC50  value were 3.17 μg/mL, 4.89 μg/mL and 5.63 μg/mL, respectively.Keywords: Anticancer  evaluation,  Hela  cell  line, Calophyllumtetrapterum.  C.  tomentosum Wight and  C. moonii

Molecular Docking of Robustaflavone Derivatives on Pi3k Protein Target and The Correlation With Its Cytotoxic Activity on Cancer Cells

Handayani, Sri ( Research Center for Chemistry, Indonesian Institute of Sciences ) , Udin, Zalinar ( Research Center for Chemistry, Indonesian Institute of Sciences )

Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

Robustaflavone  derivatives  have  cytotoxic  effect  on  cancer  cell.  Inhibition  of  PI3K  on cancer  cell  has  correlation  with  apoptotic  induction.  The  aim  of  this  research  is  to  observe interaction  from  robustaflavone  derivatives  on  PI3K  receptor  that  may  give  contribution  to  the cytotoxic effect of the compounds on cancer cell line. Geometric optimization of robustaflavone derivatives  structured  was  done  used  Hyperchem  7.5  software.  Arguslab  4.01  software  with GAdock  method  applied  for  the  docking  step.  The  docking  result  showed  that  robustaflavone 7,4,7-  trimethyl  ether  (RTE)  has  affinity  on  PI3K  target  receptor  which  gave  the  lowest  Gibbs free energy (∆G -10,855 kcal/mol).Key words: robustaflavone, PI3K, cancer, docking

Naringenin Enhances the Anti-Tumor Effect of Doxorubicin on HeLa Cervical Cancer Cells Through Cytotoxic Activity and Apoptosis Induction

Larasati, . ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada Jalan Sekip Utara Sleman Yogyakarta 555281 ) , Kusharyanti, Indri ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada Jalan Sekip Utara Sleman Yogyakarta 555281 ) , Hermawan, Adam ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada Jalan Sekip Utara Sleman Yogyakarta 555281 ) , Susidarti, Ratna Asmah ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada Jalan Sekip Utara Sleman Yogyakarta 555281 ) , Meiyanto, Edy ( Cancer Chemoprevention Research Center, Faculty of Pharmacy Universitas Gadjah Mada Jalan Sekip Utara Sleman Yogyakarta 555281 )

Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

Naringenin, an abundant flavanon in the peel of citrus fruits is reported to possess anti-proliferative  effect  in  many  cancer  cells.  Herein,  we  investigated  the  cytotoxic  effect  and apoptosis  induction  of  naringenin  in  combination  with  doxorubicin  on  HeLa  cells.  The cytotoxicity assay of naringenin, doxorubicin, and their combination were carried out by using MTT  assay.  Cell  viability  was  used  as  the  parameters  to  evaluate  combination  effectiveness. Cell  cycle  distribution  was  determined  by  flow  cytometry  and  analyzed  using  ModFit  LT  3.0 program.  Apoptosic  assay  was  done  by  double  staining  method  using  Ethidium  Bromide-Acridine  Orange.  Investigation  on  the  expression  of  Bax  and  Bcl-2  were  determined  by immunocytochemistry method. Naringenin and doxorubicin showed cytotoxic effect  on HeLa cells  with  their  IC50  values  of  195  µM  and  1  µM,  respectively.  Whereas  combination  of naringenin  -  doxorubicin  showed  greater  cytotoxicity  compared  the  single  treatment  of doxorubicin.  The  strongest  cytotoxic  activity  was  observed  at  a  combination  of  100  µM naringenin  and  0,5  µM  doxorubicin.  Single  treatment  of  0,5  µM  doxorubicin  for  24  hours  on HeLa cells induced  S-phase arrest while 100 µM naringenin did not affect on HeLa cell cycle. The  combination  induced  S-phase  arrest  with  the  increased  of  sub-G1  phase  percentage.  In accordance with the flow cytometry results, the double staining apoptosis assay results showed the increase of apoptotic cells. Naringenin, doxorubicin, and their combination also increased the  expression  of  Bax  and  decreased  the  expression  of  Bcl-2.  These  results  concluded  that naringenin was a potential co-chemotherapy agent for cervical cancer due to its synergism with doxorubicin.Keywords:  co-chemotherapy,  naringenin,  doxorubicin,  HeLa  cells,  cytotoxicity,  cell  cycle, apoptosis

Selectivity of Ethyl Acetate Fraction of Gynura Procumbens on Colon Cancer and Breast Cancer

Nurulita, Nunuk Aries ( 1)Faculty of Pharmacy, Universitas Muhammadiyah Purwokerto, Jawa Tengah, 2)Graduate Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta ) , Meiyanto, Edy ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta ) , Sugiyanto, . ( 1) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 2) Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara,Yogyakarta )

Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

Gynura  procumbens  is  widely  used  as  traditional  remedy  in  South-East  Asia.  Gynura procumbens exhibites anti inflammatory, antioxidant, and reduced blood pressure activity. The aim of this study was to determine chromatographic profile of ethyl acetate fraction of  Gynura procumbens (FEG) and to investigate its cytotoxic properties and selectivity to colon cancerand breast cancer cancer cells. The chromatographic profile of FEG was determined using HPTLC densitometric  and  HPLC.  MTT  (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium  bromide) assay was performed to determine the growth inhibitory effect of FEG on the growth of WiDr, MCF-7, and T47D cells. NIH3T3, a normal cells was used to determine the selectivity of FEG, which  contained  small  amount  of  quercetin  as  identified  from  chromatographic  profile  both HPTLC  and  HPLC.  FEG  inhibited  cell  growth  of  WiDr,  of  MCF-7  and  of  T47D  cells  in  time dependent manner. Quercetin affected cell growth inhibition approximately two fold higher at WiDr and MCF-7, whereas FEG had lower effect on T47D cell. Quercetin did not seem as the main  active  compound  of  FEG.  At  this  study,  FEG  caused  less  inhibition  on  the  growth  of NIH3T3 cells than that of on all cell lines. Selectivity index (SI) of FEG on WiDr, MCF-7 and T47D were 4.97, 2.77 and 7.79 respectively. According to the datas obtained, FEG possesses moderate to high cytotoxicity properties on WiDr, MCF-7 and T47D cells. FEG demonstrates selective  effect  against  cancer  cells  and  reveals  prospective  properties  as  cancer chemoprevention agent.Keywords: Gynura procumbens, colon cancer, breast cancer, cytotoxicity, selectivity

Combination of Leunca Herb Ethanolic Extract and Doxorubicin Suppresses HeLa Cells’ Growth

Sarmoko, . ( Department of Pharmacy, Faculty of Medicine and Health Sciences, Universitas Jenderal Soedirman, Purowokerto, Jawa Tengah, 2)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 ) , Puspitasari, Endah ( Cancer Chemoprevention Research Center, 1)Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, 2)Faculty of Pharmacy, Universitas Jember, Jember, Jawa Timur. ) , Anindyajati, . ( 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 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

Leunca (Solanum nigrum L.)ethanolic extractshowedcytotoxic activity on several cancer cell lines (HepG2, HT-29) and showed anti-proliferative activityon MCF-7 cells. Its application as a combinationagent in chemotherapy will increase  the effectivity and reduce  the toxicity of chemotherapy. We predict that application of combinatorial chemotherapy in cancer treatment will  be  more  effective  and  less  toxic  compared  to  single  treatment.  Our  research  aims  to investigate  the  cytotoxic  activitiy  of  leunca  herbs  ethanolic  extract  alone  and  in  combination with  doxorubicin  on  HeLa  cell  line.  MTT  assay  was  conducted  to  measure  the  growth inhibitory  effect  of  leunca  herbs  ethanolic  extract  and  combinatorial  treatments.  Leunca  herb ethanolic extract (5, 50, 250 μg/ml) increased the cytotoxic effect of  doxorubicin compared to doxorubicin alone. The strongest cytotoxic activity resulted from the combination of 250 μg/ml leunca  herbs  ethanolic  extract  and  250  nM  doxorubicin.  Based  on  our  results,  leunca  herbs ethanolic extract is a potential chemopreventive agent, while its molecular mechanism needs to be explored.Keyword : Leunca herbs ethanolic extract, doxorubicin, HeLa, MTT assay

In Vitro Anti-Cancer Alkaloid and Flavonoid Extracted from the Erythrina variegata (Leguminoseae) Plant

Herlina, Tati ( Department of Chemistry, Faculty of Mathematics and Natural Sciences. Padjadjaran University, Jatinangor 45363, Sumedang ) , Supratman, Unang ( Department of Chemistry, Faculty of Mathematics and Natural Sciences. Padjadjaran University, Jatinangor 45363, Sumedang ) , Subarnas, Anas ( Faculty of Pharmacy, Padjadjaran University, Jatinangor 45363, Sumedang ) , Sutardjo, Supriyatna ( Faculty of Pharmacy, Padjadjaran University, Jatinangor 45363, Sumedang ) , Amien, Suseno ( Faculty of Agriculture, Padjadjaran University, Jatinangor 45363, Sumedang ) , Hayashi, Hideo ( Laboratory of Natural Products Chemistry, Division of Applied Biological Chemistry, Graduate School of Agriculture and Life Science, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai, Osaka 599-8531, Japan )

Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

Erythrina plants, locally known as “dadap ayam”, are higher plant species and have been used as a folk medicine for treatment of cancer. To prove the effectiveness of the leaves and stem bark of E. variegata as an anti-cancer agent, the assay in this research was focused on in vitro  test  towards  breast  cancer  cell  T47D.  In  the course  of  our  continuing  search  for novel anti-cancer agent from Erythrina plants, the methanol extract of the leaves and stem bark of  E. variegata  showed  significant  anti-cancer  activity  against  breast  cancer  cell  T47D  in  vitro  using the Sulphorhodamine B (SRB) assay. By using the anti-cancer activity to follow the separations, the methanol extract was separated by combination of column chromatography. The chemical structure  of  an  anti-cancer  compounds  were  determined  on  the  basis  of  spectroscopic evidence  and  comparison  with  the  previously  reported  and  identified  as  an  erythrina  alkaloid (1)  and  isoflavonoid  (2).  Compounds  (1-2)  showed  anti-cancer  activity  against  breast  cancer cell  T47D  used  with  IC50  of    1.0  and  3.3  µg/mL,  respectively.  This  results  strongly  suggested that E. variegata is promising sources for anti-cancer agents.Keywords: Anti-cancer, Erythrina variegata, Leguminoseae

The Cytotoxic Activity of Solanum Nigrum Ethanolic Extract on Widr Human Colon Cancer Cells

Maruti, Astrid Ayu ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta Jalan Sekip Utara ) , F, Ilham Augusta ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta Jalan Sekip Utara ) , Putri, Dyaningtyas D.P. ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta Jalan Sekip Utara ) , Hermawan, Adam ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta Jalan Sekip Utara ) , Ikawati, Muthi’ ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta Jalan Sekip Utara )

Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Abstract

Solanum  nigrum  L.  or  Leunca  in  Indonesia  has  been  traditionally  used  as  a  herbal plant,  which  is  believed  to  have  anti-tumor  properties,  although  the  mechanism  for  the activity  remains  unknown.  The  resecarch  aim  to  examine  the  cytotoxic  effect  of  the ethanolic extract of Solanum nigrum on WiDr human colon cancer cells. In this study, we prepared an ethanol extract from herb of Solanum nigrum and investigated the mechanism involved  in  its  growth-inhibitory  effect  on  WiDr  human  colon  cancer  cells.  Herbs  of Solanum nigrum dry powder is extracted with 70% ethanol then added into the WiDr cell culture  in  96  wells  plate  in  various  concentration  :  50,  100,  250,  and  500  µg/ml. Cytotoxicity  of  the  Solanum  nigrum  ethanolic  extract    was  analyzed  with  MTT  assay  on WiDr human colon cancer cell lines. Results from the MTT assay showed WiDr cells was weakly  suppressed  in  the  presence of  the  extract.  The  result  of  the  assay  also  showed a very  close  correlation  between  the  Solanum  nigrum  extract  concentration  and  the surviving  cell  numbers  which  means  the  extract  caused  cell  death  in  a  dose-dependent fashion  in  WiDr  cancer  cells  with  the  IC50  of  359,23  µg/ml.  Collectively,  the  research suggest  further  studies  to  explore  other  chemopreventive possibilites  of  Solanum  nigrum ethanolic extract.Key words : colon cancer, MTT assay, cytotoxic, WiDr, Solanum nigrum