Indonesian Journal of Cancer Chemoprevention
Articles by issue : Vol 3, No 3 (2012)
6
Articles
Ursolic Acid Enhances Doxorubicin Cytotoxicity on MCF-7 Cells Mediated by G2/M Arrest

Arifin, Ibrahim ( Faculty of Pharmacy, Universitas Wahid Hasyim, Semarang ) , Hermawan, Adam ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada ) , Ikawati, Muthi ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada ) , Haryanti, Sari ( Balai Besar Penelitian dan Pengembangan Tanaman Obat dan Obat Tradisional, Tawangmangu ) , Anindyajati, . ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Meiyanto, Edy ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 3 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Ursolic acid has been widely known to possess biological activity against numerous tumor cell lines. Previous studies revealed its cytotoxicity on several cancer cells  in vitro by either inducing apoptosis or cell cycle modulation. This  study was conducted to investigate ursolic  acid’s  cytotoxicity  solely  and  in  combination  with  a  chemotherapeutic  agent, doxorubicin,  on  MCF-7  breast  cancer  cells,  followed  by  observation  on  its  mechanism. Cytotoxicity of single and combinational treatment of ursolic acid and doxorubicin on MCF-7 breast cancer cells were conducted by using MTT assay. Single treatment was then evaluated by  determining  IC50  value,  while  combinational  treatment  was  evaluated  by  analyzing  cell viability  and  evaluating  combination  index  (CI).  To  explore  the  mechanism  underlying cytotoxic  effect  on  respected  cells,  further  analysis  on  cell  cycle  profile  of  single  and combinational treatment was conducted by flow cytometry. Twenty four hours treatment of ursolic  acid  inhibited  MCF-7 cells’ growth with  IC50  value  of  37  µM,  while  combinational treatment  showed  that  several  concentration  combinations  of  ursolic  acid  and  doxorubicin exhibited  synergism  of  cytotoxic  activity  on  MCF-7  cells,  giving  optimum  CI  value  of  0.54. Flow cytometric analysis showed that combinational treatment induced G2/M arrest in MCF-7  cells.  These  results  show  that  ursolic  acid  is  promising  to  be  developed  as  either  single chemopreventive  agent,  or  as doxorubicin’s co-chemotherapeutic  agent  in  breast  cancer treatment.  Observation  on  the  selectivity  as  part  of  safety  aspect  together  with  in silico,  in vitro, and in vivo study on its molecular mechanism should be conducted.Keywords: ursolic acid, doxorubicin,co-chemotherapeutic agent, breast cancer, cell cycle

Cost Analysis of Cancer Side Effects Therapy in Cancer Patients in Rumah Sakit Prof. Dr. Margono Soekarjo Purwokerto

Pradana, Febrian ( Pharmacy Department, Faculty of Medicine and Health Sciences, Universitas Jenderal Soedirman ) , Purwonugroho, Tunggul Adi ( Pharmacy Department, Faculty of Medicine and Health Sciences, Universitas Jenderal Soedirman ) , Ekowati, Heny ( Pharmacy Department, Faculty of Medicine and Health Sciences, Universitas Jenderal Soedirman )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 3 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Cancer  is  the  leading  cause  of  death  in  Indonesia.  Generally,  cancer  therapy  use chemotherapy,  radiation,  surgery  or  combination  of  those.  Various  side  effects  caused  by cancer  therapy  make  the  use  of  additional  drugs.  This  leads  to  an  increase  in  total  cost incurred  to  cancer  patients.  The  purpose  of  this  study  was  to  describe  the  treatment  of cancer  therapy’s side effects  as  well  as  the  average  cost  of  side  effects  treatment,  and  its percentage  in  the  total  cost  of  cancer  patients  in  Rumah  Sakit  Margono  Soekarjo.  This research was a descriptive study with retrospective data  by total sampling method obtained from  patients’  medical  and  receipts  records  of  five  most  common  cancers  (breast, nasopharynx,  Non  Hodgkins  Lhympoma  (NHL),  ovarian,  and  cervix)  during  January-December 2010. The average cost of  patient’s side effects treatment was calculated by the average  cost  of  side  effects  compared  to  the  average  total  direct  costs  incurred  to  cancer patients.  The  samples  was  obtained  from  the  population  of  2261  patients  who  met  the inclusion criteria, that are 73 patients consist of 62 female patients and 11 male patients. The most  common  side  effects  of  cancer  therapy  were  nausea  and  vomiting  (59.80%),  nausea-vomiting,  anemia,  and  pain  (16.44%),  and  nausea-vomiting  and  anemia  (15.07%).  The  most used therapy was vitamin B complex followed by histamine-2 inhibitor. The average cost of side effects for breast cancer was Rp 1,715,373 (8.73%), nasopharynx was Rp 1,149,049 (6.98 %);  NHL  was  Rp  360,778  (1.97  %);  ovary  was  Rp  911,118  (3.61  %)  and  cervical  was  Rp 1,416,027 (8.87 %). The results indicated  that the hospital needs  to pay  more attention  on nausea-vomiting effect of chemotherapy, and also cervical cancer side effects therapy as the most costly.Keywords: Cost Analysis, Cancer, Side Effects, Prof. Dr. Margono Soekarjo Hospital

Ethanolic Extract of Papaya (Carica papaya) Leaves Improves Blood Cholesterol Profiles and Bone Density in Ovariectomized Rats

Sugiyanto, Raisatun Nisa ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Khamsita, Rahmi ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Susidarti, Ratna Asmah ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 3 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Bone  loss  and  disturbance  in  the  blood  cholesterol  profiles  modulation  are  two effects  caused  by  menopauses  syndromes.  As  the  estrogen  concentration  in  the  body decreased  drastically,  menopause  women  need  the  replacement  of  estrogen  to  keep  the regulation  of  several  physiological  functions  in  the  body,  such  as  bone  generation  and cholesterol  regulation  in  a  good  condition.  Phytoestrogen  in  Carica  papaya  leaves,  such  as quercetin,  could  be  one  of  the  potential  agents  for  the  estrogenic  effect.  The  aim  of  this study  is  to  know  the  effects  of  papaya  leaf  extract  (PLE)  on  the  blood  cholesterol  profiles and bone density in ovariectomized rats. Thirty six female Sprague Dawley rats divided into six groups.  The groups were sham-treated ovx (S-OVX), ovariectomized rats (OVX), CMC-Na  control  (OVX+CMC-Na),  positive  control  (OVX+Estradiol),  and  the  PLE  treatment groups  dose  750  mg/kgBW  (OVX+750mg/kgBW)  and  dose  1000  mg/kgBW  (OVX+1000 mg/kgBW).  Administrations  of  PLE  were  done  in  three  weeks  orally  and  estradiol administrated  intraperitonially.  In  the  end  of  the  treatment,  the  blood  sample  of  tested animals was collected for the blood cholesterol  determination (LDL, HDL, triglyceride, and total  cholesterol)  and  the  femur  bones  were  examined  for  the  bone  density.  Based  on  the results, PLE  dose of 750 mg/kgBW a day in ovariectomized rats showed estrogenic effects in modulating  blood  cholesterol  profile  by  lowering  total  cholesterol  levels.  Meanwhile,  PLE dose  of  1000  mg/kgBW  significantly  increased  the  bone  density  (p<0.05).  Thus,  PLE  is potential  to  overcome  the  negative  effects  of  post-menstrual  women  especially  in  the cholesterol blood profiles and bone density.Keywords : Carica papaya, phytoestrogen, bone density, blood cholesterol, ovariectomized rats

Safety Evaluation of Chicken Satay In Yogyakarta Indonesia Based on Benzo[A]Pyrene Content

Irnanda, Khairunissa ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Meiftasari, Argandita ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Nagadi, Standie ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Lukitaningsih, Endang ( Departement of Pharmaceutical Chemistry, Faculty of Pharmacy, UniversitasGadjahMada )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 3 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Chicken  satay  is  one  of  Indonesian  food  which  is  very  popular  and  processed  by direct  flame  over  the  meat.  But,  almost  every  types  of  food  which  are  prepared  by  direct flame  will  produce  chemical  compounds  that  contributes  to  the  incidence  of  cancer. Polycyclic aromatic hydrocarbons (PAH) is a group of compound which can cause cancer and is  resulted  from  the  incomplete  combustion  of  fossil  fuels  or  pyrolysis  of  organic  material containing  carbon  and  hydrogen  atoms.  One  PAH  compound  having  mutagenic  and  highly carcinogenic  effect  is  benzo[a]pyrene  which  is  the  highest  content  found  in  foods  that  are burned directly on the flame. This study aims to establish levels of benzo[a]pyrene contained in  chicken  satay  in  Yogyakarta,  Indonesia  and  to  evaluate  how  it  meets  with  the maximumbenzo[a]pyrene  limit  in  the  burned  food  based  on  National  Agency  of  Drug  and Food  Control  which  is  equal  to  5  ppb  (5  mg/kg).  Analysis  were  performed  by  Gas Chromatography  method  using  helium  as  carrier  gas  and  CPCB-Sil8  as  stationary  phase. After  the  sample  was  prepared  and  analysed  by  GC,  it  is  known  that  the  amount  of benzo[a]pyrene in chicken satay found in Yogyakarta are ranging from 2.5 to 393.32 ppb. The result are quite high and far  above the safety limit determined by  National Agency of Drug and Food Control.Therefore, the result of the research needs to be socialized to the public so that people can be more aware about the danger of food they consume.Keywords: chicken  satay,  benzo[a]pyrene  (BaP),  policyclic  aromatic  hidrocarbon  (PAH), carsinogen, Yogyakarta

Elettaria cardamomum Distillate Increases Cellular Immunity in Doxorubicin Treated Rats

Raksamiharja, Rikat ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Sy, Khairunnisa ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , S, Meirizky Zulharini ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Novarina, Annisa ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Sasmito, Ediati ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 3 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Doxorubicin is one of chemotherapeutic agent used for cancer therapy. However, doxorubicin usage causes some adverse effects, such as lymphocyte, CD4+ and CD8+ cells number.  Therefore,  the  co-chemotherapeutic  agent  is  required  to  reduce  the imunosuppression  effect.  Cardamom  (Elettaria  cardamomum)  contains  terpenoid  1,8  cineol. This  research  aimed  to  know  the  effect  of  Elettaria  cardamomum  distillate  (ECD)  in combination with doxorubicin on Sprague Dawley rat’s hematology profile and the amount of CD4+  and  CD8+  cells.  The  experiment  was  done  for  13  days  using  6  groups  of  rats:  I doxorubicin (dox) 15 mg/kg BW; II dox + ECD5 mg/kg BW; III dox + ECD 50 mg/kg BW; IV dox  +  ECD  100  mg/kg  BW;  V  ECD  100  mg/kg  BW;  VI  control  without  treatment.  The hematology  profile  and  the  amount  of  CD4+  and  CD8+  were  counted  before  and  after treatment  using  flowcytometer.  The  results  show  that  ECD  increases  the  amount  of lymphocyte, white blood, CD4+ and CD8+ cells in dose dependent manner in doxorubicin treated rats. Based on the data, it can be concluded that ECD is potential to be developed as immunostimulant agent for chemotherapy.Keywords: Cardamom (Elettaria cardamomum), immunostimulant, hematology, CD4+, CD8+

Ethanolic Extract of Secang (Caesalpinia sappan L.) Wood Performs as Chemosensitizing Agent Through Apoptotic Induction on Breast Cancer MCF-7 Cells

Khamsita, Rahmi ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Hermawan, Adam ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada ) , Putri, Dyaningtyas Dewi Pamungkas ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Meiyanto, Edy ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 3 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Resistance  to  chemotherapy  is  believed  to  cause  treatment  failure  of  the  patient cancer. Secang (Caesalpinia sappan L.) has been proven to possess anticancer activity on some cancer cell lines. The aimed of this study to develop ethanolic extract of secang wood (EES) as  chemosensitizing  agent  through  apoptotic  induction  on  breast  cancer  MCF-7  cells. Extraction  of  secang  was  done  by  using  maceration  with  70  %  ethanol.  Single  and combinatorial treatment of EES and doxorubicin on MCF-7 breast cancer cells were analyzed by using MTT assay to determine the IC50 value and combination index (CI) to evaluate the combinatorial effect. Apoptosis was analyzed with flowcytometry (annexin V).  EES showed a dose-dependent cytotoxicity (IC50 value of 37 µg/ml), while combinatorial treatment showed that  7  concentrations  was  found  to  be  synergist  with  doxorubicin  on  MCF-7  cells. Combinatorial treatment also triggered apoptotic instead of single treatment. Based on this result,  we  conclude  that  ethanolic  extract  of  secang  wood  is  potential  as  chemosensitizing agent in breast cancer.Keyword: Caesalpinia sappan L, MCF-7 cells, doxorubicin, apoptosis.