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PENINGKATAN EFEK SITOTOKSIK DOXORUBICIN OLEH NARINGENIN MELALUI PEMACUAN APOPTOSIS SEL KANKER PAYUDARA MCF-7

Jurnal Bahan Alam Indonesia Vol 7, No 3 (2010)
Publisher : Indonesian Research Gateway

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Abstract

Chemoterapic agent doxorubicin has a lot of side effects and resistance problem. Therefore, it is important to develop combination treatment of doxorubicin with natural product (co-chemotheraphy) such as naringenin. Naringenin has been proven to have cytotoxic activity against several cancel cell lines. Naringen also increase the sensitivity of MCF-7 breast cancer cell towards doxorubicin. The aim of this research is to examine the synergistic effect of naringenin on the cytotoxic activity of doxorubicin through apoptosis induction of MCF-7 cancer cell lines.The cytotoxic assay of naringenin and doxorubicin were carried out by MTT method using naringenin concentrations of 100-1250 μM and doxorubicin concentrations of 50-800 nM to determine the IC50. Based on the IC50 values, the cytotoxic assay of their combination were carried out  by MTT method using concentration of ⅛, ¼, ⅜ and ½ IC50 values. Apoptosis assay of their best combination concentrations were done using double staining method.Naringenin and doxorubicin showed cytotoxic effect on MCF-7 breast cancer cell with IC50 of 520 μM and 467 nM, respectively. Based on CI values, almost all concentration combination of naringenin and doxorubicin showed synergistic effect (CI 0,1-0,9). This synergistic effect is due to the induction of apoptosis, showed by the increasing number of orange fluorescence cells in double staining method. Based on this results, naringenin was potential to be delevoped as co-chemotherapeutic agent. However, the molecular mechanism need to be explored further.

ISOLASI DAN IDENTIFIKASI FRAKSI TERAKTIF DARI FRAKSI KLOROFORM KULIT BATANG BAKAU MERAH (Bruguiera gymnorrhiza) DAN AKTIVITAS SITOTOKSIKNYA

Jurnal Bahan Alam Indonesia Vol 8, No 1 (2012)
Publisher : Indonesian Research Gateway

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Abstract

ABSTRACTThe chlorofom fraction of red bakau (Bruguiera gymnorrhiza) bark has anticancer activity, but its anticancer compounds have not been publicated. Thus, research needs to be done to isolate, identify the most active fraction of chloroform extract from red bakau merah bark and determine its compounds by gas chromatography-mass spectrometry (GC-MS) method. The methods used in this research are partition, column chromatography, thin layer chromatography, cytotoxic activity on HeLa cells, and GC-MS. The F2 fraction are potential as anticancer drugs with LC50 values are 69 μg/mL, respectively. Mass spectrograms of F2 fraction show that F2 fraction containts 1,4 tioxan sulfoxida, ß-caryophyllene and cholest-14-en-3-01.Keywords : chloroform fraction, Bruguiera gymnorrhiza, fractionation, identification, cytotoxic activity ABSTRAKFraksi kloroform dari ekstrak metanol kulit batang bakau merah (Bruguiera gymnorrhiza) memiliki aktivitas antikanker tetapi senyawa antikanker yang terkandung dalam fraksi aktif dari fraksi kloroform tersebut belum dipublikasikan. Penelitian ini bertujuan untuk mengetahui senyawa yang terdapat dalam fraksi aktif dari hasil isolasi fraksi kroloform dan aktivitas sitotoksiknya terhadap sel kanker HeLa. Penelitian ini meliputi 2 tahap, yaitu tahap fraksinasi yang meliputi metode partisi, kromatografi kolom, kromatografi lapis tipis, dan identifikasi senyawa dengan GCMS dan tahap uji aktivitas sitotoksik menggunakan kultur sel HeLa dengan metode MTT. Hasil uji sitotoksik menunjukan fraksi aktif (F2) dapat menghambat pertumbuhan sel HeLa dan berpotensi sebagai antikanker dengan nilai LC50 sebesar 69 μg/mL dan fraksi tersebut mengandung senyawa 1,4 tioxan sulfoxida, ß-caryophyllene dan cholest-14-en-3-01.Kata kunci : fraksi kloroform, bakau merah (Bruguiera gymnorrhiza), fraksinasi, identifikasi, aktivitas sitotoksik.

In vivo Antiplasmodial of the Most Active Fraction and Its Compound of Kapur Leaves (Harmsiopanax aculeatus Harms) Extract Against Plasmodium berghei

Tropical Medicine Journal Vol 1, No 2 (2011): Tropical Medicine Journal
Publisher : Fakultas Kedokteran bekerjasama dengan PETRI

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Abstract

Introduction : The rising of Plasmodium resistance towards chloroquine and other antimalarial drugs have encouraged to discover and develop new drugs mainly derived from natural products. Harmsiopanax aculeatus (kapur plant) has traditionally used by people of in Maluku Province to treat malaria.Objectives: The aims of this study were to identify antiplasmodial activity and its chemical constituents of the most active fraction of kapur leaves.Methods: The dried powder of Kapur leaves (1.3 kg) were extracted successively by maceration with n-hexane, ethyl acetate and methanol. After removal the solvents the hexane 15.6 g (1.2%), ethyl acetate 53.3 g (4.1%) and methanol 61.1 g (4.7%) extracts were obtained. Those extracts were assayed for their in vivo antiplasmodial activities by using 4-days suppressive test in Swiss mice infected with Plasmodium berghei, HPIA and identified the compound by GC-MS.Results: The ED50 of hexane, ethyl acetate and methanol extracts were 467.58, 2074.02 and 16.16 mg/kgBW, respectively. Fractionation of the methanol extract gave 18 combined fractions (FG1 – FG18). FG8 was the most active fraction with the IC50 HPIA of 18.22 μg/ml. Phytochemical test of this fraction using spray reagent showed the existence of essential oils, triterpenoids, and phenolic compounds. Separation of FG8using pressed chromatography gave 19 combined fractions (FG8.1-FG8.19). The fraction containing intense blue fluorescent spot (FG8.5) was further separated by PLC fourthly eluted with chloroform. Seven major components with the percentage of compotition more than 3.11% were identified as eugenol (tr = 12.692; 18.22%), isoprophyl myristate (tr = 16.333; 3.99%); bis(2-methylpropyl) phtalat (tr = 16.939; 7.15%); methyl palmitic (tr = 17.442; 3.11%); palmitic acid (tr = 17.883; 25.72%); butyl 2-methylpropyl phtalat (tr = 17.957; 9.37%) and bis(2-ethylhexyl) phtalat (tr = 23.258; 23%).Conclusion: Methanol extract of H. aculeatus was the most potential in vivo antiplasmodial activity. Combined fraction 8 which contain 7 compounds was the most active fraction.Keywords: Harmsiopanax aculeatus Harms, in vivo antiplasmodial, HPIA, PLC, GC-MS

SynergisticCombinationofCiplukan(Physalis angulata) HerbsEthanolicExtractandDoxorubicinonT47DBreast CancerCells

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

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Abstract

Doxorubicinisoneofchemotherapeuticagentwidelyusedinbreastcancertreatment,but in high dose doxorubicin gives negative side effect, including vomit, nausea, immune suppression, and cardiac toxicity. This toxicity hopefully could be reduced by combination chemotherapy using natural herbs such as ciplukan herb. This research was conducted to explorecytotoxicactivityofsingleciplukanherbsethanolicextractanditscombinationwith doxorubicinonT47Dbreastcancercells.Cytotoxicactivityofciplukanherbsethanolicextract only and its combination with doxorubicinwere tested on T47D cells using MTT assay toobtainIC50valueandcombinationindex(CI),respectively.Singleextractshowedcytotoxic activityonT47DcellswithIC50valueofwas160*g/ml.Thus,combinationtreatmentfrom ciplukanherbsethanolicextractanddoxorubicinshowedsynergisticeffect(CI<1,0).Thiseffect wasreachedatconcentrationofciplukanherbsethanolicextract-doxorubicin80μg/ml-2nM, 80 μg/ml-4 nM, and 80 μg/ml-8 nM. This research indicated that ciplukan herbs ethanolic extractispotentialtobeappliedasco-chemotherapeuticagentinbreastcancertherapy.

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

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

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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.

Hesperidin Increases Cytotoxic Activity of Doxorubicin on Hela Cell Line Through Cell Cycle Modulation and Apoptotis Induction

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

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Abstract

Combination of chemotherapeutic agent and chemo preventiveagent is being a new approach in cancer treatment.This is aimed at enhancing the effectivity and also reducing drugresistance and adverse side effect of the chemo therapeuticagent.Hesperidin,acitrus flavonoid has reported to reduce theproliferation of many cancer cells.The objectives of this study were to investigate cytotoxic activities, cell cycle modulation and apoptosis induction of he speridinand its combination withdoxorubicinon Helacelllines.MTT [3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazoliumbromide] assay was used tomeasure the growth inhibitory effect of he speridinanditscombination with doxorubicinon Helacells.Cellcycle profile was determined by flowcytometry and the dataobtained was analyzed by using Mod Fit LT3.0program.Apoptos is assay was done using double staining method usingethidium$bromideandacridine$orange.Hesperidin inhibited cellgrowth with IC5048M, while the IC50 of doxorubicin was 1000nM.Combination of 500n Mdoxorubicin and 6M hesperidin showed strongest inhibitory effect toward Hela cells. Hesperidin of 24 2M accumulated HeLacells at G1phase,butit scombinationwith 500nM Doxorubicin gave G1 and Sphase accumulation at 24h incubation.Both of Hesperidin and Doxorubicin were capable of inducing apoptosis.Inaccordance of the apoptoticeffect,hesperidin,doxorubicin and their combination decreasedthe expression Bcl$2 and increased the expression of Bax. Accordingtothisresult,hesperidinhasapotencytobedevelopedasco$chemotherapeutic agent forcervical cancer. Key    words:Cochemotherapy,Hesperidin,Doxorubicin,Hela,MTTassay

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

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

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

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

Combination of Doxorubicin and Areca Ethanolic Extract Induces Apoptosis by Increasing Caspase-3 Level on Breast Cancer (T47D) Cells

Indonesian Journal of Cancer Chemoprevention Vol 3, No 1 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Despite causing many side effects, doxorubicin (Dox) is still one of breast cancer drug of choice. Thus, combination of chemotherapy is developed in order to decrease doxorubicin regimen dose. The aim of this research is to examine the combination effect of doxorubicin (dox) and areca extract (AE) on T47D human breast cancer cells. The cytotoxic activity was determined using MTT assay. The combination index (Cl) of the combination treatment was calculated to determine the effects (synergistic, additive or antagonistic). The combination application of dox (6-22nM) and AE (8-30μg/ml) on T47D cells showed synergistic (Cl<0.9) or addictive effect )Cl =0.9-I.I). The effective combincation of dox-AE was 6nM-8μg/ml on Cl<0.5. Apoptosis induction of AE solely and its combination with dox was the observed using double staining method. Moreover, expression of Bax and caspase-3 protein which mediated apoptosis, were observed using immunocytochemistry. Combination of AE and Dox increased expression of Caspase-3 but did not increase expression of Bax. This result showed AE increase the effectiveness of doxorubicin against T47D cells.Keyword : Breast cancer, doxorubicin, areca extract, T47D cells

The Safety of Areca Seed Ethanolic Extract as Potential Chemopreventive Agent is Proven by Acute Toxicity Test

Indonesian Journal of Cancer Chemoprevention Vol 3, No 1 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Areca (Areca catechu L.) seeds ethanolic extract (AE) exhibits antiproliferative activity and induces apoptosis on T47D and MCF-7 cells. This study aimed to verify AE safety using acute toxicity test to support its development as chemopreventive agent. Male Sprague Dawley Rat 9Rattus norvegicus) age 8 weeks divided into five groups, one group of control treated with 0.5 % CMC-Na only and four groups for treatment. Single dose in oral administration was done to test animal with various dose of AE starts from lowest dose to highest dose expected toxic to all of test animal (0.1; 0.72; 5.36 and 10 gram/kgBW). Observation was done during 24 hours and continued for 14 days. The observation criteria were toxic symptoms, appearance and mechanism of toxic effect and pathology of vital organ. Histopathology analysis of some vital organs was done with Haematoxyllin & Eosin (H&E) staining. Toxic effect did not appear either on treatment groups or control group. Treatment of single dose of areca ethanolic extract, even in highest dose, did not cause the death of the animals. Therefore, observation extended to 14 days and terminated by necroption of the animals. All of group did not show histopathological alterations in microscopic observation. Category of the potential toxicity of AE is practically non-toxic, ie 10 g/kgBW. The result show the safety of areca seed ethanolic extract which is important for its development as chemopreventive agent.Key words: Areca catechu, acute toxicity, rat