Muthi Ikawati
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada

Published : 11 Documents
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Aktivitas Antiproliferasi Ekstrak Etanolik Herba Ciplukan (Physalis angulata L.) Terhadap Sel Hepar Tikus Betina Galur Sprague Dawley Terinduksi 7,12-Dimetilbenz[a]antrasena Fauzi, Ilham Agusta; Amalia, Fikri; Sabila, Nurma; Hermawan, Adam; Ikawati, Muthi; Meiyanto, Edy
Majalah Kesehatan Pharmamedika Vol 3 N0 1 2011
Publisher : Majalah Kesehatan Pharmamedika

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One of the natural materials as potentially efficacious chemopreventive agents are Ciplukan (Physalis angulata L.). Several previous studies reported that Physalis angulata L. herbs ethanolic extract (PEE) has cytotoxic activity and induction of apoptosis in breast cancer cells MCF-7 and HeLa cervical cancer cells. This study aims to determine the effects of  PEE as an chemopreventive agent on rat liver cells induced 7,12-dimetilbenz[a]anthracene (DMBA). This study used Sprague Dawley strain female rats aged 40-50 days were divided into 5 groups : (1) DMBA control group, mice were induced with DMBA in per oral dose of 20 mg/kg; (2) DMBA + PEE dose 750 mg/kgBW group ; (3) DMBA + PEE dose 1500 mg/kgBW group ; (4) solvent control group of CMC-Na 0,5%; (5) PEE dose 1500 mg/kgBW control group. PEE was dissolved in CMC-Na 0,5% and administered daily, starting the seventh week after administration of DMBA. At the beginning of  the tenth week of the study, rats were necropted and liver organs were isolated and stored in buffered formalin 4%. Qualitative analysis to determine the histopathology of liver cells through staining method of Hematoxyllin & Eosin (HE), while quantitative analysis to determine the level of liver cell proliferation by AgNOR staining method. The results showed in the DMBA control group that liver cell morphology changes that hiperproliferation leading to carcinogenesis. In DMBA + PEE dose of  1500 mg/kgBW group improved the situation of DMBA-induced liver cells histopathology and antiproliferation activity better than DMBA + PEE dose of 750 mg/kgBW on DMBA-induced rat liver cells. The results showed that Physalis angulata L. herbs ethanolic extract can inhibit cell proliferation in rat liver caused by DMBA administration through antiproliferation mechanism and have potential for the development as chemoprevention material on liver cancer
Taraxacum officinale Leaves Ethanolic Extract as Immunostimulatory Agent For Reducing Side Effect of Doxorubicin in Sprague Dawley Rats Kasianningsih, Sri; Rivanti, Erlina; Pratama, Ratih Hardika; Pratama, Nanda Resa; Ikawati, Muthi; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 2, No 1 (2011)
Publisher : Indonesian Research Gateway

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Doxorubicin as chemotherapeutic agent causes immunosuppresive. The aim  for this study to determine the effect of ethanolic extract of Taraxacum oficinale (ETO) in immunity system of Sprague Dawley  rat that induced  by doxorubicin to observe the profile of immunity cells. Sprague Dawley rats were divided into five groups each groups contain five rats : control doxorubicin group, doxorubicin dose 4,67 mg/kgBW+ ETO dose 1000 mg/kgBW, doxorubicin dose 4,67 mg/kgBW+ ETO dose 500 mg/kgBW, control extract group, and without treatment. Then the number of leukocytes, lymphocytes and neutrophils were analyzed  by hematology analyzer, whereas CD8+ T lymphocytes by flowcytometry. Results showed groups of  doxorubicin combined with ETO dose 1000 mg/kgBW and 500 mg/kgBW increased the number of leukocytes, lymphocytes, neutrophils,  cytotoxic CD8 + T cells  T cells compared  to control doxorubicin group. These data presents that etanolic extract of Jombang leaves has  immunostimulatory activity and potential as co-chemotherapy agents. Molecullar mechanism underlaying it’s immune activity need to be explored in detail.
Banana Peels (Musa paradisiaca L.) Extract as Phytoestrogen on Ovariectomized Mice Mammary Gland Development by Inducing c-Myc Expression Pratama, Nanda Resa; Gilang, Yurista; Riata, Rita; Hermawan, Adam; Ikawati, Muthi; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 2, No 1 (2011)
Publisher : Indonesian Research Gateway

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Hormone Replacement Therapy (HRT) is therapy for estrogen deficiency and post menopausal  syndromes,  but  high  cost  and  unwell-secured  therapy.  One  of  alternative therapy  is  the  usage  of  phytoestrogens.  The  banana  peel  contains  flavones,  flavonol, flavanone and polimethoxyflavone which are potential as phytoestrogen. The purpose of this study was to examine the estrogenic effect of banana peel extract (BPE) development of mammary gland of ovariectomized rats. Estrogenic effects was examined based on in vivo and in silico experiment. For in vivo experiment, female Sprague-dawley rats aged 50 days were ovariectomized. At 70 days of age, 12 rats were treated with BPE 500 mg/kgBB and 1000mg/kgBB, 5 rats were treated with estradiol 2g/day while others served as control were treated with CMC-Na 0.5% and sacrificed 2 weeks later. The base line ovariectomized rats and base line non-ovariectomized rats were sacrificed at 70 days of age. The in silico experiment examined by molecular docking between myricetin and estrogen receptor alpha (ER-α). The result of in vivo experiment showed that 1000 mg/kgBW BPE induced c-Myc expression  and  enhance  ovariectomized  rat  mammary  gland  development  significantly. Meanwhile, molecular docking showed that there are hydrogen bond interaction between bioactive compound in BPE and Estrogen Receptor (ER)-α but less powerfull than estrogen and ER-α interaction. In summary, BPE can act as an estrogen agonist,  resulting in the enhancement of c-Myc expression. 
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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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
Cytotoxicity of Tetrahydropentagamavunon-0 (THPGV)-0 and Tetrahydropentagamavunon-1 (THPGV-1) in Several Cancer Cell Lines Ikawati, Muthi; Purwanto, Heri; Imaniyyati, Niar Nurul; Afifah, Anis; Sagiyo, Marrita Langgeng; Yohanes, Jasson; Sismindari, Sismindari; Ritmaleni, Ritmaleni
Indonesian Journal of Pharmacy Vol 29 No 4, 2018
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1198.508 KB) | DOI: 10.14499/indonesianjpharm29iss4pp179

Abstract

Tetrahydropentagamavunon-0 (THPGV-0) and Tetrahydro-pentagamavunon-1 (THPGV-1), are analogs of a curcumin metabolite, tetrahydrocurcumin, and a derivate of Pentagama-vunon-0 (PGV-0) and Pentagamavunon-1 (PGV-1), respectively.  THPGV-0 and THPGV-1 have been successfully synthesized and are investigated for their anticancer potency.  Cytotoxic assays were performed toward several cancer cell lines to determine values of the IC50 against those cell lines. Assessing cytotoxicity in Vero normal cell line showed the selectivity of those compound.  THPGV-1 showed highest cytotoxic activity in lymphoma Raji cells, a suspension cell line, with an IC50 of 180mM.  Both THPGV-0 and THPGV-1 showed similar potencies in T47D breast cancer cell line with IC50 values of 250-270mM.  Regardless their high selectivity, however, cytotoxic activities of THPGV-0 and THPGV-1 were lower compared to PGV-0 and PGV-1 in HeLa cervical, T47D breast, and WiDr colon cancer cell lines.  Further study using different types of cancer cell lines and confirmation of cell viability by another assays and apoptosis detection may give more benefit. 
Ekstrak Air J amur Ling Zhi (Ganoderma lucidum (Leysser) Karsten) Meningkatkan Persentase Sel Limfosit T CD8+ Relatif pada Tikus yang Dipejani Doxorubicin IKAWATI, MUTHI; KARAMITA, ANNISA; EDIATI, EDIATI; SUSIDARTI, RATNA ASMAH
JURNAL ILMU KEFARMASIAN INDONESIA Vol 9 No 1 (2011): JIFI
Publisher : Fakultas Farmasi Universitas Indonesia

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Pengobatan kanker dengan agen kemoterapi sering menimbulkan berbagai macam efek samping yang merugikan, termasuk imunosupresi. Penggunaan imunostimulan bersama dengan agen kemoterapi (ko-kemoterapi) dapat menjadi alternatif untuk mengatasinya. Ganoderma lucidum (jamur Ling Zhi) dilaporkan menunjukkan aktivitas imunostimulan. Penelitian ini bertujuan untuk mengevaluasi aktivitas imunostimulan ekstrak air G. lucidum dengan menentukan persentase sel limfosit T CD8+ relatif pada hewan uji yang dipejani doxorubicin. Ekstraksi bahan tanaman dilakukan dengan metode infusa. Tikus betina galur Sprague Dawley dibagi dalam 6 kelompok, yaitu kelompok kontrol doxorubicin, kontrol pembanding produk komersil, perlakuan ekstrak dosis 100 mg/kgBB dan 450 mg/kgBB, kontrol ekstrak, dan kontrol tanpa perlakuan. Persentase sel limfosit T CD8+ relatif dari sampel darah diukur dengan flow cytometry menggunakan program Multiset. Data dianalisis secara statistik dengan t test dan one way ANOVA, dilanjutkan Post Hoc test. Hasil penelitian menunjukkan bahwa ekstrak air G. lucidum mampu meningkatkan persentase sel limfosit T CD8+ relatif pada tikus yang dipejani doxorubicin. Ekstrak air G. lucidum menjanjikan untuk dikembangkan sebagai agen imunostimulan ko-kemoterapi.
Sinergisme Fraksi Butanol Metabolit Sekunder Kapang Endofit 1.3.11 dengan Doxorubicin dalam Modulasi Daur Sel T47D dan MCF-7 KUMALA, SHIRLY; MEIYANTO, EDY; IKAWATI, MUTHI; JENIE, RIRIS ISTIGHFARI
JURNAL ILMU KEFARMASIAN INDONESIA Vol 8 No 1 (2010): JIFI
Publisher : Fakultas Farmasi Universitas Indonesia

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The synergic effects of n-butanolic fraction of secondary metabolite of endophytic fungus 1.3.11 (FB) and doxorubicin (Dox) on cell cycle regulation and the expression of Bcl-2 gene expression were investigated on MCF-7 and T47-D cells by iiow cytometry and immunocytochemical techniques respectively. The results showed that after 12 hours of incubation period with FB at its IC50 dose, MCF-7 cell cycle was inhibited at G1 phase while Dox inhibited the cell cycle at G2/M phase. Similar results were observed in T47-D cells when incubated with Dox and FB individually under the same treatment condition. Further treatment was then performed to these cells where both Dox and FB were combined at their IC50 and  lC50 dose and added to incubate with the cells over 12 hours period. Interestingly, the modified treatment combination showed that MCF-7 and T47-D cell cycle regulation were inhibited at G2/M phase. Our immunocytochemical study also showed no significant inhibition suppression of Bel-2 gene expression in both MCF-7 and T47-D cells when compared with their corresponding positive control after treatment with FB and Dox or both combined FB and Dox at 1C50 and  IC50 dosage over 15 hours incubation.
Ekstrak Etanolik Daun Awar-Awar (Ficus septica Burm F.) secara Sinergis Meningkatkan Efektivitas Doxorubicin terhadap Sel Kanker Payudara T47D PRATAMA, RATIH HARDIKA; IKHTIARSYAH, YURISTA GILANG; ANINDYAJATI, ANINDYAJATI; FITRIASARI, ADTYA; IKAWATI, MUTHI; MEIYANTO, EDY
JURNAL ILMU KEFARMASIAN INDONESIA Vol 9 No 1 (2011): JIFI
Publisher : Fakultas Farmasi Universitas Indonesia

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Daun awar-awar (Ficus septica Burm E), yang belum dimanfaatkan secara optimal dalam pengobatan kanker, memiliki potensi untuk digunakan sebagai agen kombinasi dengan doxorubicin. Penelitian ini bertujuan untuk mengetahui efek sitotoksik ekstrak etanolik daun awar-awar (EDA) dan kombinasinya dengan agen kemoterapi doxorubicin (DOX) pada sel kanker payudara T47D. EDA diperoleh dari maserasi serbuk kering daun awar-awar dengan etanol 70%. Pengujian aktivitas sitotoksik ekstrak dilakukan dengan MT T assay, baik perlakuan tunggal maupun kombinasinya dengan DOX. Sifat sitotoksik ditentukan dengan nilai IC50, sementara efektivitas kombinasi dihitung dengan nilai indeks kombnasi (CI) untuk menetapkan apakah efeknya sinergis, aditif, atau antagonis. Uji sitotoksik perlakuan EDA tunggal selama 24 jam menunjukkan efek sitotoksik yang potensial dengan IC50 sebesar 13 µg/mL. Kombinasi EDA-DOX menunjukkan efek sinergis (CI < 1) pada konsentrasi EDA 4,88 µg/mL dan DOX 3.75 nM. Hasil ini menunjukkan bahwa EDA memiliki potensi yang menjanjikan untuk diaplikasikan sebagai agen ko-kemoterapi DOX pada terapi kanker payudara.
Anti-metastatic Profiles of Boesenbergia pandurata towards MCF-7/HER2 Cells Fadliyah, Hilyatul; Putri, Nindya Budiana; Walidah, Ziana; Nurhayati, Ika Putri; Ikawati, Muthi; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 9, No 2 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1130.75 KB) | DOI: 10.14499/indonesianjcanchemoprev9iss2pp68-77

Abstract

The development of breast cancer at an advanced stage is signed with metastatic phenomenon, triggering the high mortality, mainly for Human Epidermal Growth Factor Receptor (HER)2 positive cancers. Boesenbergia pandurata is well known as medicinal plant possessing anticancer potential due to the cytototoxic and antimetastatic characteristic of its active compound. The aim of this study is to observe the inhibitory effect of Boesenbergia pandurata ethanolic extract (BPEE) in combination with doxorubicin on migration of MCF-7/HER2 cells. The BPEE was prepared by 96% ethanol maceration. Under MTT assay, BPEE decreased the cells viability with IC50 value of 23±3.9 μg/mL. Lamellipodia and wound healing assay analysis showed that 5 μg/mL BPPE and its combination with 10 nM doxorubicin inhibited cells migration after 48 hours observation, while gelatin zymography analysis showed that this combination did not affect the expression of Matrix Metalloproteinase (MMP)2 and MMP9, but single treatment of 5 μg/mL BPEE caused lower expression of both MMPs. The combination of 5 μg/mL BPPE and 10 nM doxorubicin inhibited the cells migration but not affect to the cells viability. Thus, BPEE is potential to be developed as an antimetastatic agent. The mechanism underlying the migratory inhibition effect needs to be explored further.Keywords : Boesenbergia pandurata, doxorubicin, MCF-7/HER2, migrationSubmitted:
Pentagamavunone-0 (PGV-0), a Curcumin Analog, Enhances Cytotoxicity of 5-Fluorouracil and Modulates Cell Cycle in WiDr Colon Cancer Cells Ikawati, Muthi; Septisetyani, Endah Puji
Indonesian Journal of Cancer Chemoprevention Vol 9, No 1 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (264.043 KB) | DOI: 10.14499/indonesianjcanchemoprev9iss1pp23-31

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The use of 5-fluorouracil (5-FU) in colon cancer as the primary chemotherapy has not been meet satisfactory effectiveness.  Therefore, the development of new chemicals as a chemopreventive agent and a combination agent (co-chemotherapeutic agent) for colon cancer is important.  Pentagamavunone-0 (2,5-bis-(4'-hydroxy-3'-methoxybenzylidine) cyclopentanone) (PGV-0), one of curcumin analogs, exhibits cytotoxic effect and apoptosis induction in various cancer cell lines, including colon cancer cell, better than curcumin.  This study aimed to investigate the cytotoxic potency of PGV-0 in combination with 5-FU and their effects, in single or in combination, on cell cycle toward WiDr colon cancer cell line.  The cells were treated with combination concentrations of PGV-0 and 5-FU, and examined by MTT cell viability assay.  The value of combination index (CI) as a parameter of cytotoxic combination assay was measured by a combination index method.  Cells were stained with propidium iodide and the cell cycle distribution was determined by flowcytometry. CI calculation showed additive effects between PGV-0 and 5-FU.  Combination of PGV-0 and 5-FU gave synergism on cell cycle.  Single treatment of PGV-0 increased apoptosis, illustrated as subG1-phase accumulation, stronger than single treatment of 5-FU.  Meanwhile, combination of PGV-0 and 5-FU demonstrated S-phase arrest.  Based on these results, it can be concluded that PGV-0 has the potential to be developed as a co-chemotherapeutic agent for colon cancer but still requires further tracking of its molecular mechanisms.Keywords: Pentagamavunone-0 (PGV-0), 5-fluorouracil (5-FU), colon cancer,combination, cell cycle