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All Journal Farmasains : Jurnal Farmasi dan Ilmu Kesehatan Journal of Food and Pharmaceutical Science Indonesian Journal of Cancer Chemoprevention Indonesian Journal of Tropical and Infectious Disease Majalah Obat Tradisional INDONESIAN JOURNAL OF PHARMACY The Indonesian Biomedical Journal JFIOnline Journal of Food and Pharmaceutical Sciences
Ratna Asmah Susidarti
Faculty Of Pharmacy, Universitas Gadjah Mada
Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Earth & Planetary Sciences Health Professions Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology Neuroscience Public Health

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SynergisticCombinationofCiplukan(Physalis angulata) HerbsEthanolicExtractandDoxorubicinonT47DBreast CancerCells Armandari, Inna; Palupi, Kartika Dyah; Farida, Sofa; Hermawan, Adam; Susidarti, Ratna Asmah; Meiyanto, Edy
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 Nur, Kholid Alfan; Putri, Herwandhani; Cahyani, Fany Mutia; Katarina, Aulia; Susidarti, Ratna Asmah; Meiyanto, Edy
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 Kusharyanti, Indri; Larasati, .; Susidarti, Ratna Asmah; Meiyanto, Edy
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 Warsinah, .; Sismindari, .; Susidarti, Ratna Asmah
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 Larasati, .; Kusharyanti, Indri; Hermawan, Adam; Susidarti, Ratna Asmah; Meiyanto, Edy
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 Rahmi, Fitria; Meiyanto, Edy; Susidarti, Ratna Asmah
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 Handayani, Sri; Jenie, Riris Istighfari; Susidarti, Ratna Asmah
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
Ethanolic Extract of Papaya (Carica papaya) Leaf Exhibits Estrogenic Effects In Vivo and In Silico Sugiyanto, Raisatun Nisa; Khamsita, Rahmi; Lambertus, Marvin; Utomo, Rohmad Yudi; Susidarti, Ratna Asmah
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 Papaya (Carica papaya) Leaves Improves Blood Cholesterol Profiles and Bone Density in Ovariectomized Rats Sugiyanto, Raisatun Nisa; Khamsita, Rahmi; Susidarti, Ratna Asmah
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
PENGARUH MEDIA PADA PERTUMBUHAN FUNGI ENDOFIT IP-2 DAN PRODUKSI METABOLIT AKTIF INHIBITOR POLIMERISASI HEM Purwantini, Indah; Wahyono, Wahyono; Mustofa, Mustofa; Susidarti, Ratna Asmah
Majalah Obat Tradisional Vol 20, No 1 (2015)
Publisher : Faculty of Pharmacy, Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (794.469 KB) | DOI: 10.14499/mot-TradMedJ20iss1pp%p

Abstract

Endophytic fungus IP-2 is the endophytic fungus isolated from the plant Artemisia annua L. This fungus is known to have activity as an inhibitor of heme polymerization. The aim of this study is to examine the suitable medium for the growth and production of the active metabolite and to determine the appropriate time for harvesting the active metabolite. Endophytic fungus was fermented in 4 types of media for 14 days. Sampling was taken every day to obtain the weight of the dry cells which were used for analysis of growth. The media obtained is used to determine their activities as heme polymerization inhibitor. Tests were carried out using the method developed by Bassilico et al (1998). Data of dry cell weight and the percentage inhibition of heme polymerization were analyzed in order to obtain the curve of growth and metabolite production. Both curves will be used to determine the proper time to harvest the active metabolite. The results showed that the PDB was the best medium for endophytic fungus IP-2 growth and was able to produce the active metabolite higher than most other media. In the PDB media, at day-7 showed that active metabolite produced at most so that proper harvest time metabolite is on the 7th day of fermentation.
Co-Authors . Larasati . Sismindari . Warsinah Abdul Karim Zulkarnain Abdul Manaf Ali, Abdul Manaf Abdul Rohman Adam Hermawan Aditya Fitriasari Agung Endro Nugroho Agustina Setiawati Agustina Styawan, Anita Alfi Yasmina Aulia Katarina Edy Meiyanto Endah Puji Septisetyani, Endah Puji Fany Mutia Cahyani Fitria Rahmi Harsan, Hayfa Salsabila Herwandhani Putri Ika Puspitasari Indah Purwantini Indri Kusharyanti Inna Armandari Kartika Dyah Palupi Kholid Alfan Nur Marchaban, Marchaban Martono, Sudibyo Marvin Lambertus Meiyanto, Edy Meiyanto, Edy Mintarsih, Betty Mintarsih, Betty Muflikhasari, Haruma Anggraini Mustofa Mustofa Mustofa, Mustofa Muthi Ikawati Nasrudin, Nasrudin Octa Ujiantari, Navista Sri Pamungkas P, Dyaningtyas Dewi Pramono, Suwidjiyo Purwanto Rahmah, Inggita Hasi Rahman, Faaza Aulia Rahmani, Mawardi Rahmani, Mawardi Rahmawati, Desty Restia Rahmi Khamsita Raisatun Nisa Sugiyanto Rianti, Andrih Riris Istighfari Jenie Rohmad Yudi Utomo Sarmoko Sarmoko Sendy Junedi Sofa Farida Sri Handayani Sukari, Mohd. Aspollah Sukari, Mohd. Aspollah Sunarni, Titik Triutomo, Devyanto Hadi Wahyono Wahyono Wahyono, Wahyono Wahyuono, Subagus Wibowo, Andy Eko Windarsih, Anjar Zufairo, Shofa Khamdanatuz