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Selectivity of Ethyl Acetate Fraction of Gynura Procumbens on Colon Cancer and Breast Cancer Nurulita, Nunuk Aries; Meiyanto, Edy; Sugiyanto, .
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, .; Putri, Dyaningtyas D. P.; Puspitasari, Endah; Anindyajati, .; Meiyanto, Edy
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
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
Secang (Caesalpinia sappan L.) Heartwood Ethanolic Extract Shows Activity as Doxorubicin Co-chemotherapeutic Agent by Apoptosis Induction on T47D Breast Cancer Cells Nurzijah, Ika; Putri, Dyaningtyas Dewi Pamungkas; Rivanti, Erlina; Meiyanto, Edy
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. 
Ursolic Acid Enhances Doxorubicin Cytotoxicity on MCF-7 Cells Mediated by G2/M Arrest Arifin, Ibrahim; Hermawan, Adam; Ikawati, Muthi; Haryanti, Sari; Anindyajati, .; Meiyanto, Edy
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
Ethanolic Extract of Secang (Caesalpinia sappan L.) Wood Performs as Chemosensitizing Agent Through Apoptotic Induction on Breast Cancer MCF-7 Cells Khamsita, Rahmi; Hermawan, Adam; Putri, Dyaningtyas Dewi Pamungkas; Meiyanto, Edy
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.
Translational Research in Cancer Drug Development Meiyanto, Edy; Hermawan, Adam; Anindyajati, .
Indonesian Journal of Cancer Chemoprevention Vol 2, No 2 (2011)
Publisher : Indonesian Research Gateway

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Abstract

The development of cancer treatment were initiated by the existence of human’s effort to treat by applying certain materials which is mostly part(s) or extracts of plants, which are now adapted as traditional herbal medicine. The discovery of new drugs was based on intuition and empirical evidence. Thus, high luck factor was involved in a successful treatment with unguaranteed reproducibility. One example of drug being developed through conventional drug development is Taxol. Taxol is an extremely complex natural product and requires a bunch of hard work with high level of serendipity to be discovered as antitumor agent. Recently, rapid development in human biology and technology allow a change in drug discovery strategy by minimizing the luck factor. Targeted therapy has been a very promising strategy of drug development research, especially in cancer treatment. Although cancer has been known as a disease with very complex cellular and histo-pathophysiology, the abundance of studies on proteins, such as receptors and hormones, as the hallmarks of cancer allows us to explore carcinogenesis suppression further based on molecular targeted therapy. Kinases, one type of protein involved in signal transduction regulating cell growth and differentiation, could be the proteins that  are proposed to be inhibited in suppressing tumor growth. An interesting example of the drug being discovered based on molecular modeling is the discovery of lapatinib as anti-cancer with specific target on HER-2 and EGFR to overcome the resistance of cancer  to Herceptin caused by elevated level of EGFR expression.
PGV-0 AND PGV-1 INCREASED APOPTOSIS INDUCTION OF DOXORUBICIN ON MCF-7 BREAST CANCER CELLS Meiyanto, Edy
Pharmacon Vol 12, No 2 (2011)
Publisher : Pharmacon

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Abstract

As chemotherapeutic backbone for breast cancer therapy, doxorubicin showed various side effects and induced resistancy of breast cancer cells. Development of targeted therapy on breast cancer focused on combinatorial therapy of doxorubicin and molecular targeted agents. PGV-0 and PGV-1, a curcumin analogue showed potency as co-chemotherapeutic agent with doxorubicin. Our previous study of PGV-0 and PGV-1 showed cytotoxic activity in T47D cells. Therefore, the aim of this research is to examine the synergistic effect of PGV-0, PGV-1 on the cytotoxic activity of doxorubicin through cell cycle modulation and apoptotic induction on MCF-7 breast cancer cell lines. The cytotoxic assay of PGV-0, PGV-1, doxorubicin, and their combination were carried out by using MTT assay. Cell cycle distribution and apoptosis were determined by flowcytometer FACS-Calibur and the flowcytometry data was analyzed using Cell Quest program. Single treatment of PGV-0, PGV-1 and doxorubicin showed cytotoxic effect on MCF-7 with cell viability IC50 value 50 µM, 6 µM and 350 nM respectively. Single treatment of Doxorubicin 175 nM induced G2/M arrest. Single treatment of PGV-0 5 µM induced G2/M arrest while in higher dose 12.5  µM, PGV-0 induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 5 µM induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 12.5 µM also increased apoptosis induction. Single treatment of PGV-1 0.6 µM induced G1 arrest while in higher dose 1.5  µM, PGV-1 induced apoptosis. Combination of doxorubicin 175 nM and PGV-1 0.6 µM induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 1.5 µM also increased apoptosis induction. PGV-0 and PGV-1 are potential to be delevoped as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle modulation, but the molecular mechanism need to be explored detail.  Key words: PGV-0, PGV-1, doxorubicin, co-chemotherapy, breast cancer, cell cycle arrest, apoptosis
DOCKING KURKUMIN DAN SENYAWA ANALOGNYA PADA RESEPTOR PROGESTERON: STUDI INTERAKSINYA SEBAGAI Selective Progesterone Receptor Modulators (SPRMs) Meiyanto, Edy
Pharmacon Vol 13, No 2 (2012)
Publisher : Pharmacon

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Abstract

Kurkumin merupakan suatu kandungan dari Curcuma longa L.,yang telah dibuktikan efek sitotoksiknya secara in vitro terhadap sel kanker payudara. Senyawa analog kurkumin: PGV-0, PGV-1, HGV-0, dan HGV-1, hasil modifikasi dari kurkumin, diperkirakan memiliki aksi yang sama. Penelitian ini bertujuan untuk mengetahui afinitas dan interaksi dari kurkumin dan analognya sebagai Selective Progesterone Receptor Modulators (SPRMs) dalam mengadakan inhibisi kompetitif dengan hormon progesteron. Optimasi geometri struktur kurkumin dan analognya dilakukan dengan software Hyperchem 7.5. Konformasi optimum PGV-0 dan PGV-1 dihasilkan melalui metode AM1 sedangkan kurkumin, HGV-0, dan HGV-1 dengan metode PM3. Kemudian dilakukan proses docking senyawa uji dengan bindingsite hormon progesteron pada reseptor progesteron (IA28) menggunakan software Arguslab 4.01, dalam kondisi ada dan tanpa air. Proses ini dilakukan dengan metode GAdock. Dari proses docking diperoleh nilai (Gibbs free energy)DG terendah pada senyawa kurkumin bentuk keto baik dengan maupun tanpa air. Afinitas terbesar turunan kurkumin ditunjukkan oleh PGV-1 pada keadaan ada air dan  HGV-1 tanpa air pada reseptor progesteron. font-family: "Arial","sans-serif";mso-ansi-language:IN>Kata kunci: kurkumin dan analognya, SPRMs, docking, reseptor  progesteron IA28 -language:IN>Antiradikal, DPPH, IC50, fenolik total, Elephantopus schaber L., Ocimum basilicum L.forma citratum Back., Graptophylum pictum Griff, Gynura procumbens Merr. 
POTENSI KEMOPREVENTIF EKSTRAK ETANOLIK KULIT JERUK KEPROK (Citrus reticulata) PADA KARSINOGENESIS SEL HEPAR TIKUS GALUR SPRAGUE DAWLEY TERINDUKSI DMBA Meiyanto, Edy
Pharmacon Vol 12, No 1 (2011)
Publisher : Pharmacon

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Abstract

Salah satu titik tangkap strategi penemuan agen kemopreventif kanker khususnya kanker hepar adalah melalui penghambatan proliferasi dan penekanan ekspresi onkogen c-Myc. Tangeretin, nobiletin, dan hesperidin adalah beberapa senyawa aktif dari kulit jeruk keprok (Citrus reticulate) dilaporkan memiliki efek antiproliferatif pada berbagai sel kanker secara in vitro. Hasil penelitian ini dapat bermanfaat untuk mengetahui efek ekstrak etanolik kulit C. reticulata terhadap proliferasi dan penekanan ekspresi c-Myc pada sel hepar tikus betina galur Sprague Dawley berumur 40 hari terinduksi 7,12 Dimetilbenz[a]antrasen (DMBA). Tikus dikelompokan menjadi lima kelompok: (a) DMBA, tikus diinduksi DMBA secara peroral (p.o.), dengan dosis 20 mg/kgBB dalam minyak jagung, sebanyak 10 kali selama lima minggu(b) kontrol pelarut CMC-Na, (c) kontrol ekstrak dosis 1500 mg/KgBB, (d) DMBA+ekstrak 750 mg/kgBB,dan (e) DMBA+ekstrak              1500 mg/kgBB. Ekstrak dilarutkan dengan CMC-Na 0,5% dan diberikan setiap hari, dimulai minggu kelima setelah pemberian DMBA. Tikus dikorbankan saat awal minggu kesepuluh setelah pemberian DMBA. Organ hepar diisolasi dan diawetkan dengan buffer formalin untuk analisis proliferasi dan imunohistokimia c-Myc. Analisis antiproliferasi dilakukan dengan metode AgNOR dan hasil menunjukan bahwa ekstrak etanolik kulit C. reticulata dosis 750 mg/KgBB memiliki potensi tinggi dalam menghambat proliferasi dan menekan ekspresi onkogen c-Myc. Hasil ini menunjukkan bahwa ekstrak etnolik kulit Citrus reticulata dapat menghambat proliferasi pada sel hepar tikus akibat pemberian DMBA melalui efek antiproliferasi dan penekanan ekspresi c-Myc..Kata kunci: Citrus reticulata, antiproliferatif, DMBA, AgNOR, c-Myc.
Co-Authors . Anindyajati . Larasati . Sugiyanto Adam Hermawan Adam Hermawan Aditya Fitriasari Aditya Fitriasari Agung Endro Nugroho Agusta Fauzi, Ilham Ainun Wulandari Alexxander, . Alexxander, . Ameilinda Monikawati Ameilinda Monikawati Andita Pra Darma Andita Pra Darma Andriyani, Rina Angelina, Marissa Arief Nurrochmad Arief Rahman Hakim Asih Triastuti Astrid Ayu Maruti Aulia Katarina Aulia Rahman, Faaza Ayu Maruti, Astrid B. Sudarto Banun Kusumawardani D., Andita Pra D., Andita Pra Da'i, Muhammad Da’i, Muhammad Dewi Arum Sekti, Dewi Arum Dewi Pamungkas Putri, Dyaningtyas Dewi Pratiwi Dini Maharani Djaswadi Dasuki Dwi Ana Nawangsari Dwi Ana Nawangsari, Dwi Ana Dwi Merry Christmarini Robin Dwi Nurahmanto Dyaningtyas D. P. Putri Dyaningtyas Dewi Pamungkas Putri Dyaningtyas Dewi Putri Pamungkas Effendi, Fatiha Citra Endah Puji Septisetyani, Endah Puji Endah Puspitasari Endang Lukitaningsih Endang Purwaningsih Erlina Rivanti Erna Prawita Setyowati Faaza Aulia Rahman Fany Mutia Cahyani Farmasyanti, Cendrawasih Andusyana Feby Handoko, Fransiscus Fikri Amalia Fina Aryani Goenadi Fina Aryani Goenadi, Fina Aryani Fitria Rahmi Fiveri, Anis Fiveri, Anis Fortunella Tjondro Hanaan Emilia Adi Hastuti Handayani, Sri Handayani, Sri Hanifa, Mila Hargiani, Fransisca Xaveria Harsan, Hayfa Salsabila Hendra Kurniawan Maury Hendri Wasito Heni Susilowati Herwandhani Putri Herwandhani Putri Ibrahim Arifin Ida Ayu Putu Sri Widnyani Ika Nurzijah Ika Rahmawati Sutejo Ilham Agusta Fauzi Ilham Agusta Fauzi Imono Argo Donatus, Imono Argo Indri Kusharyanti Inna Armandani, Inna Inna Armandari Iwan Sahrial Hamid JAKA WIDADA Jauhari, Fahmi Ihsanuddin Jenie, Riris Istighfari Jenie, Riris Istighfari Juni Ekowati Kadarsih Soejono, Sri Kadarsih Soejono, Sri Kartika Dyah Palupi Kartika Dyah Palupi Kholid Alfan Nur Kholid Alfan Nur Komang Alit Paramitasari Kuijpers-Jagtman, Anne Marie Kumara, Dennaya Laras Widawaty Putri Lestari, Dinda Luthfia Indriyani M, Kawaichi M, Kawaichi Mae Sri Hartati Wahyuningsih Marcellino Rudyanto Maria Dwi Supriyati Maria Dwi Supriyati, Maria Dwi Maria Indra Ardriyanto Masashi Kawaichi Masashi Kawaichi, Masashi Muhammad Da'i Muhammad Fithrul Mubarok, Muhammad Fithrul Muthi Ikawati N., Perdana Adhi N., Perdana Adhi Nabila, Klarissa Nanda Resa Pratama Niken Nur W, Niken Novi Hastuti, Novi Novianti, Metta Novitasari, Dhania Nunuk Aries Nurulita Nunuk Purwanti Nurma Sabila P.K.W., Diah Ayu P.K.W., Diah Ayu Perdana Adhi Nugroho Perdana Adhi Nugroho Prasetyaningrum, Pekik Wiji Pudjono Pudjono Putri, Herwandhani R A Susidarti Raditya Prima Istiaji Rahmi Khamsita Ratih Hardika Pratama Ratna Asmah Susidarti Ratna Asmah Susidarti Retno Ardhani Retno Murwanti Rifai, Fauziah Novita Putri Riris I Jenie Riris I Jenie, Riris I Riris Istighfari Jenie Riris Istighfari Jenie Riris Istighfari Jenie Risdian, Chandra Rita Riata Rohmad Yudi Utomo Rohmad Yudi Utomo Rosa Adelina Rosana Anna Ashari Rosana Anna Ashari, Rosana Anna Rosye H.R. Tanjung Rul Afiyah Syarif Sari Haryanti Sari Haryanti Sarmoko Sarmoko Sendy Junedi Sendy Junedy, Sendy Shigeru Sasaki Sismindari . Sitarina Widyarini Sofa Farida Sri . Handayani Sri Handayani Sri Kadarsih Soejono Sri Kasianningsih Sri Susilowati Sri Tasminatun Sugeng Riyanto Sugiyanto . Sugiyanto . Sukardiman Supardjan A. M. Supardjan A.M., Supardjan Supardjan AM Supardjan AM, Supardjan Susi Ari Kristina Taro Kawai Tutuk Budiati Udin, Zalinar Umar A. Jenie Umar Anggara Jenie Umar Anggara Jenie Umar Anggara Jenie Widayanti, Wasita Rachma Yundari, Yundari Yurista Gilang Yurista Gilang Ikhtiarsyah Yuyun Farida Yuyun Farida, Yuyun Zulfin, Ummi Maryam