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Indonesian Journal of Cancer Chemoprevention
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68
Articles
Antiproliferative Effect of Ethanolic Extract Eugenia uniflora Lam. Leaves on T47D Cells

Ismiyati, Nur ( Department of Pharmacy Politeknik Kesehatan Bhakti Setya Indonesia Yogyakarta ) , Putri, Dyaningtyas Dewi Pamungkas ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada ) , Kusumastuti, Siska Andrina ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada ) , Febriansyah, Rifki ( Universitas Muhammadiyah Yogyakarta )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Eugenia uniflora Lam. is one of herbal products developed for anticancer. The aim of the present study was to identify the antiproliferative effect of ethanolic extract of Eugenia Uniflora Lam. leaves (EEU) on breast cancer cell line T47D. This Research was initiated by extracting the active contents of Eugenia uniflora Lam. leaves by maceration with ethanol 96%. The extract was then analyzed by thin layer chromatography (TLC). Cytotoxic assay of EEU was carried out by using MTT assay. Apoptosis phenomenon was observed with double staining using acridine orange-ethidium bromide. EEU showed cytotoxic effct on T47D cells with IC50 value of 65 μg/ml. Moreover, EEU 50 μg/ml and 100 μg/ml induced apoptosis. TLC examination showed that EEU used in this study contain phenolic, flavonoid, and saponin compounds which were suggested to be responsible for antiproliferative effect. Further molecular mechanism underlying EEU antiproliferative effect needs to be done.Keywords : Eugenia uniflora Lam., T47D cells, antiproliferative, apoptosis

Secang (Caesalpinia sappan L.) Heartwood Ethanolic Extract Shows Activity as Doxorubicin Co-chemotherapeutic Agent by Apoptosis Induction on T47D Breast Cancer Cells

Nurzijah, Ika ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada ) , Putri, Dyaningtyas Dewi Pamungkas ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada ) , Rivanti, Erlina ( 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 2 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Doxorubicin, primary chemoteurapeutic agent used for breast cancer treatment, is known to have various side effects included multi drug resistance 9MDR) phenomenon. Therefore, exploration of co-chemotherapeutic agent is important to be conducted in order to prevent MDR. Secang (Caesalpinia sappan L.) which contains active compounds brazilin and brazilein, is proven to have activity as anticancer. The aim of this study is to determine the potency of Caesalpinia sappan L.ethanolic extract (CEE) as co-chemotherapeutic agent of doxorubicin and its mechanism through apoptosis induction on T47D breast cancer cells. Caesalpinia sappan L. heartwood powder was macerated with ethanol 70%. The cytotoxic effect of CEE alone and its combination with doxorubicin was analyzed using MTT assay. Apoptosis assay was done by flowcytometry-annexin V method. CEE showed cytotoxic activity on T47D cells with IC50 value of 35 μg/ml, while combinatorial test showed that all of combination doses of CEE and doxorubicin gave synergistic effect. Flowcytometry-annexin V assay proved that treatment of CEE induced apoptosis of doxorubicin. Based on these results, we conclude that Caesalpinia sappan L. heartwood ethanolic extract is potential to be developed as co-chemotherapeutic agent of doxorubicin.Keywords : Caesalpinia sappan L., doxorubicib, apoptosis, T47D cells. 

Ethanolic Extract of Papaya (Carica papaya) Leaf Exhibits Estrogenic Effects In Vivo and In Silico

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 ) , Lambertus, Marvin ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada ) , Utomo, Rohmad Yudi ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada ) , Susidarti, Ratna Asmah ( Departement of Pharmaceutical Chemistry Faculty of Pharmacy Universitas Gadjah Mada )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Research Gateway

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Abstract

The menopause women have the low level of estrogen in the body. The lack of estrogen changes physiological function in womens body that affects in health condition. Carica papaya L. leaf contains flavonoid quercetin which exhibits estrogenic effect. The aim of this study is to determine the estrogenic effect of papaya leaves extract (PLE) in vivo, and in silico. Papaya leaves were extracted by ethanol 70% maceration. The in silico study were done by molecular docking between quersetin and Estrogen Receptor (ERα and ERß) to obtain the docking score. Based on this study, docking score of quercetin was almost similar to the native ligand of ER. The in vivo study was done as follow: 36 female rats Sprague Dawley divided into six groups. The groups are shame-ovariectomized (S-OVX), control ovariextomized (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, while estradiol was administrated intraperitonially. The mammae and uterine were sliced for analysis. Based on the study, the treatment of PLE increased the number of mammae lobules and uterine weight as well as estrogen does. In summary, PLE can be developed as a source of phytoestrogens.Keywords: Carica papaya L., phytoestrogen, estrogen receptor, mammae lobule, uterine

Ethanolic Extract of Mangosteen (Garcinia mangostana) Peel Inhibits T47D and Hela Cells Line Proliferation Via Nf-kB Pathway Inhibition

Rivanti, Erlina ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada ) , Rohmah, Annishfia Lailatur ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada ) , Putri, Herwandhani ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada ) , Tirtanirmala, Prisnu ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada ) , Pamungkas, Dyaningtyas Dewi Putri ( Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Effective and selective chemoterapeutic and chemopreventive agent is needed to cure breast and cervical cancers. One of the potential natural material is mangosteen peel (Garcinia mangostana). In this study, we observed cytotoxic effect of ethanolic extract of mangosteen peel (EMP) on HeLa cells line and T47D cells line. The cytotoxic effect was determined using MTT assay. EMP showed cytotoxic effect on T47D cells and HeLa cells with IC50 values of 2.07 μg/ml and 10.58 μg/ml respectively. Molecular docking simulation was done to predict the molecular mechanism of active compund in mangosteen peel extract, α-mangostin, in NFκB pathway which is one of the potential pathway to induce cytotoxicity on T47D and HeLa cells. Docking was done using PLANTS software and the binding score between α-mangostin and proteasom is -78,12, whereas the binding score between α-mangostin and IKK is -86.84. These results showed the possiblity mechanism of mangostin peel extract containing α-mangostin inhibits IKK activation in NFκB pathway. Based on this study, we conclude that mangosteen peel extract is potential to be developed as chemopreventive agent toward cervical and breast cancers.Keywords : Mangosteen peel (Garcinia mangostana), cytotoxic, T47D cells, HeLa cells, NFκB

The Number of Macrophages and Heterophils on Chick Embryo Chorioallantoic Membrane After Gynura procumbens (Lour) Merr Extract Treatment and bFgF Induction

Hamid, Iwan Sahrial ( Division of Basic Veteriner, Faculty of Veterinary, Universitas Airlangga ) , P, Yuseni Kusuma ( Faculty of Veterinary, Universitas Airlangga, Surabaya ) , Bijanti, Retno ( Division of Basic Veteriner, Faculty of Veterinary, Universitas Airlangga ) , Aksono, E Bimo ( Division of Basic Veteriner, Faculty of Veterinary, Universitas Airlangga )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Antiangiogenesis (inhibition of new blood vessels formation) has become a strategy to inhibit cancer development. The aim of this experiment was to investigate antiangiogenic effect  of  Gynura  procumbens  (Lour)  Merr  focusing  on  the  decreasing  of  the  number  of macrophages  and  heterophils  on  chick  embryo  chorioallantoic  membrane.  Nine-days-aged-eggs  were  divided  into  six  groups  (eight  eggs  each  group).  Group  I  (positive  control)  eggs were  induced  with  bFGF+Tris  HCl.  Group  II  (negative  control)  eggs  were  treated  with DMSO+Tris  HCl.  Group  III  (treatment  I)  eggs  were  induced  with  60  ng  bFGF  and  treated with  ethanolic  extract  of  G.  procumbens  leaves  with  the  dose  of  60  µg.  The  following treatment  groups,  i.e.  group  IV  (treatment  II),  group  V  (treatment  III),  and  group  VI (treatment IV) were treated with increasing dose of extract, starting from 75 µg, 90 µg, and the last was 110 µg. Eggs were incubated until they reach the age of twelve days to observe macrophages, while  to observe heterophils, eggs were incubated until  the  age of seventeen days. Based on haematoxylin-eosin staining, macrophages in the treatment groups were less than the control positive group (bFGF+Tris HCl), but based on giemsa staining, the effect of Gynura procumbens  in decreasing the number of heterophils could not  be observed  because some blood smears. These analysis suggest that  the  ethanolic extract of  Gynura procumbens leaves can perform as antiangiogenic agent decreasing the number of macrophages.Keywords: antiangiogenic, macrophages, heterophils, Gynura procumbens

Hesperidin Increases Cytotoxic Effect of 5-Fluorouracil on WiDr Cells

Gilang, Yurista ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta ) , Hermawan, Adam ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta ) , Fitriasari, Aditya ( Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta ) , Jenie, Riris Istighfari ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta )

Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Therapy  of  colon  cancer  by  using  5-FU  often  causes  problems  of  resistance.  This encourages the development of co-chemotherapy agent. One of the compounds that could potentially be used as a co-chemotherapy agent  is hesperidin. This study was conducted to determine the cytotoxic effects of hesperidin, 5-FU and the combination of them, as well as apoptosis induction in colon cancer cells WiDr. Cytotoxic effect of hesperidin, 5-FU, and its combination were observed using MTT assay. Observation of apoptosis was done by double staining method using ethidium bromide-acridin orange. Until 48 hours incubation, hesperidin showed no cytotoxic effects. Cytotoxic effects of 5-FU was observed after 48 hours with the IC50 value of 422 µM. However, hesperidin improved the cytotoxic effects of 5-FU at 48 hour incubation.  Either  single  treatment  of  hesperidin  200µM  or  5-FU  1500  µM  did  not  trigger apoptosis, but combination of them led to the emergence of signs of apoptosis. Based on this study,it can be concluded thathesperidin is potential to be developed as a co-chemotherapy agent of 5-FU on colon cancer but still need further study on its molecular mechanisms.Keywords : hesperidin, 5-fluorouracil, WiDr cells, cytotoxic, apoptosis

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