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All Journal Indonesian Journal of Cancer Chemoprevention Journal of Mathematical and Fundamental Sciences Indonesian Journal of Biotechnology Majalah Obat Tradisional Journal of Tropical Biodiversity and Biotechnology INDONESIAN JOURNAL OF PHARMACY The Indonesian Biomedical Journal JURNAL MANAJEMEN DAN PELAYANAN FARMASI (Journal of Management and Pharmacy Practice) JPSCR : Journal of Pharmaceutical Science and Clinical Research JFIOnline Jurnal Ilmu Kefarmasian Indonesia Majalah Kesehatan Pharmamedika
Muthi Ikawati
Faculty Of Pharmacy, Universitas Gadjah Mada
Agriculture, Biological Sciences & Forestry Astronomy Biochemistry, Genetics & Molecular Biology Chemistry Earth & Planetary Sciences Environmental Science Health Professions Immunology & microbiology Materials Science & Nanotechnology Mathematics Medicine & Pharmacology Physics Public Health

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Ursolic Acid Enhances Doxorubicin Cytotoxicity on MCF-7 Cells Mediated by G2/M Arrest Ibrahim Arifin; Adam Hermawan; Muthi' Ikawati; Sari Haryanti; Anindyajati Anindyajati; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 3, No 3 (2012)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev3iss3pp410-418

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
Citrus Flavonoids from Citrus reticulata Peels Potentially Target an Autophagy Modulator, MAP1LC3A, in Breast Cancer Bayu Anggoro; Dennaya Kumara; Dhella Angelina; Muthi Ikawati
Indonesian Journal of Cancer Chemoprevention Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev12iss3pp114-122

Abstract

Citrus flavonoids have been known for their vast biological activities including chemoprevention activities. However, the organic solvent extraction system limits its potential utilization. We recently adopted a hydrodynamic-cavitation method to extract citrus flavonoids from citrus peels. In this study we verified the high flavonoid content of the hydrodynamic-cavitation extract from Citrus reticulata peels and explore the potency of its citrus flavonoid contents as targeted chemoprevention agent for breast cancer by using bioinformatics. Based on a thin layer chromatography, the extract positively yielded high content of citrus flavonoids represented by hesperidin. The toxicity analysis by Protox II Online Tool revealed that hesperidin as the major citrus flavonoid in the extract was considered safe with a predicted LD50 of 12,000 mg/kg. We then further exploring citrus flavonoids’ capacity in targeting MAP1LC3A, a key protein in autophagy. UALCAN analysis validated that low expression of MAP1LC3A is associated with low survival rates in breast cancer patients. Limonin, hesperidin, narirutin, neohesperidine, and naringin are flavonoids from citrus peels that predicted to have inhibitory activity against Protein Kinase A (PKA), a negative upstream of MAP1LC3A, calculated by KNIME. Citrus flavonoids scoparone, cirsimaritin, 4',5,7-trimethoxyflavone, eupatorine, and hesperidin were also exhibit similar structure to an agonist of ATG4B, a protein that plays a role in MAP1LC3A activation. Furthermore, eupatorine, hesperidin, and cirsimaritin displayed a high affinity to ATG4B based on a molecular docking. We concluded that citrus flavonoids from citrus peels are safe to normal cells, and the citrus flavonoids potentially targets MAP1LC3A by inhibiting PKA and acting as ATG4B agonists. Thus, this extract-contained flavonoids from citrus peels is potential to be investigated further as a chemoprevention agent by inducing autophagy, especially for breast cancer.Keywords: Citrus reticulata, citrus flavonoid, autophagy, MAP1LC3A, breast cancer.
Pentagamavunone-0 (PGV-0), a Curcumin Analog, Enhances Cytotoxicity of 5-Fluorouracil and Modulates Cell Cycle in WiDr Colon Cancer Cells Muthi Ikawati; Endah Puji Septisetyani
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 | DOI: 10.14499/indonesianjcanchemoprev9iss1pp23-31

Abstract

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
Indonesian Micromelum minutum Leave Extracts and Their Cytotoxic Activities toward Breast Cancer Cell Lines Ratna Asmah Susidarti; Edy Meiyanto; Muthi' Ikawati; Normaidah; Nurramadhani Armada Sida
Journal of Mathematical and Fundamental Sciences Vol. 53 No. 1 (2021)
Publisher : Institute for Research and Community Services (LPPM) ITB

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.5614/j.math.fund.sci.2021.53.1.8

Abstract

Isolation and identification of compounds and pharmacological activity of the Micromelum minutum grown in some countries has been done, but the Indonesian M. minutum has not been studied, either phytochemically or pharmacologically. This study aimed to determine the cytotoxic activity of Indonesian M. minutum leave extracts toward MCF-7 and 4T1 breast cancer cell lines. The leaves were obtained from M. minutum grow in Bantimurung National Park, Bulusaraung, South Sulawesi, and then were macerated gradually in hexane, ethyl acetate, and methanol. The cytotoxic activity of obtained extracts was determined by MTT assay. The extraction yielded hexane (HEM), ethyl acetate (EEM), and methanol (MEM) extracts of 2.65, 6.12, and 6.49%, respectively. HEM was the most potent extract with IC50 values of 148 and 87 µg/mL on MCF-7 and 4T1 cells, respectively, followed by EEM (185 and 170 µg/mL). MEM possessed a weak potency with an IC50 value of 384 µg/mL on MCF-7 cells and was not toxic toward 4T1 cells. Therefore, HEM is important to be further investigated for its active constituents.
Chemical Constituents of Indonesian Micromelum minutum Leaves and Their Cytotoxicity Against MCF-7 and 4T1 Breast Cancer Cells Ratna Asmah Susidarti; Edy Meiyanto; Muthi' Ikawati; Normaidah; Nurramadhani Armada Sida
Journal of Mathematical and Fundamental Sciences Vol. 53 No. 1 (2021)
Publisher : Institute for Research and Community Services (LPPM) ITB

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.5614/j.math.fund.sci.2021.53.1.7

Abstract

Micromelum minutum is used widely in traditional folk medicine. Although this species has been investigated extensively and several bioactive compounds have been isolated, little work has been done on Indonesian M. minutum. This research aimed to study the chemical constituents and biological activities of M. minutum cultivated in Bantimurung Bulusaraung National Park, South Sulawesi, Indonesia. The isolated compounds were assessed for their cytotoxicity towards MCF-7 and 4T1 cell lines by MTT method. The dried ground leaves of M. minutum were sequentially macerated with n-hexane, ethyl acetate, and methanol. The n-hexane and ethyl acetate extracts contained a flavonoid 5,7-dihydroxy-3,4',8-trimethoxyflavone (1) which inhibited MCF-7 and 4T1 cell viability by 50% at concentrations of 369±8 and 227±5 µM, respectively. Further separation of the ethyl acetate extract by column chromatography yielded acetyldihydromicromelin A (2) and a mixture of dihydromicromelin A (3) and dihydromicromelin B (4), which were not active toward MCF-7 and 4T1 cells.
The potency of Pentagamavunone‐0 (PGV‐0) as chemopreventive agent for the formation and growth of breast cancer as revealed in 3D model Wulandari Wulandari; Muthi’ Ikawati; Edy Meiyanto
Indonesian Journal of Biotechnology Vol 25, No 1 (2020)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijbiotech.51759

Abstract

Pentagamavunone‐0 (PGV‐0) or 2,5‐bis(4’‐hydroxy‐3‐methoxybenzylidine)‐cyclopentanone is a curcumin analogue that exhibits anticancer activity in breast cancer cells. However, most of previous reports are limited to the use of two‐dimensional (2D) cell culture. The use of three‐dimensional (3D) cell culture model in cancer research can represent the real condition of cancer growth in patients better than the 2D culture. The purpose of this study was to determine the anticancer activity of PGV‐0 on a 3D model of HCC 1954 breast cancer cells. HCC 1954 cells were grown in the 3D culture in the presence of PGV‐0, and the spheroid formation and growth of formed spheroids were observed using microscope at 24 and 96 h, respectively. The cytotoxic effects were measured by MTT assay. PGV‐0 inhibited the formation and growth of spheroids at the concentration as low as 60 µM. The cytotoxic effect of PGV‐0 appeared in a dose‐dependent manner with the IC50 value of 70.9 µM. The results of this study indicate that PGV‐0 has an anticancer activity on a 3D model of HCC 1954 breast cancer cell line. Therefore, the result supported the potency of PGV‐0 as cancer chemopreventive agent.
Ekstrak Etanolik Daun Awar-Awar (Ficus septica Burm F.) secara Sinergis Meningkatkan Efektivitas Doxorubicin terhadap Sel Kanker Payudara T47D RATIH HARDIKA PRATAMA; YURISTA GILANG IKHTIARSYAH; ANINDYAJATI ANINDYAJATI; ADTYA FITRIASARI; MUTHI IKAWATI; EDY MEIYANTO
JURNAL ILMU KEFARMASIAN INDONESIA Vol 9 No 1 (2011): JIFI
Publisher : Fakultas Farmasi Universitas Pancasila

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1432.224 KB)

Abstract

Awar awar leaves which have not been optimally utilized in cancer treatment, are potential to be used in combination with doxorubicin (DOX), an agent used for chemotherapy. The aim of this experiment is to find out cytotoxic effect of awar-awar leaves ethanolic extract (ALE) and its combination with DOX towards breast cancer cells of T47D. ALE was prepared by macerating the dried-leaves powder with ethanol 70%. The cytotoxic effect of ALE toward breast cancer cells was tested employing MTT assay to the treatments both as a single agent and as a combination with doxorubicin (ALE DOX). The cytotoxicity was determined as IC50 value, while effectiveness of combination was measured by combination index (CI) to determine whether the effect is synergic, addictive, or antagonistic. Cytotoxic tests on single treatment ALE for a period of 24 hours resulted to a cytotoxic effect with IC so value of 13 µg/mL. ALE-DOX combination showed synergistic effect (CI < 1) on the concentration of 4.88 µg/mL (ALE) and 3.75 nM (DOX). The results showed that ALE is potential to be used as doxorubicin co-chemotherapeutic agent in breast cancer therapy.
Ekstrak Air J amur Ling Zhi (Ganoderma lucidum (Leysser) Karsten) Meningkatkan Persentase Sel Limfosit T CD8+ Relatif pada Tikus yang Dipejani Doxorubicin MUTHI IKAWATI; ANNISA KARAMITA; EDIATI EDIATI; RATNA ASMAH SUSIDARTI
JURNAL ILMU KEFARMASIAN INDONESIA Vol 9 No 1 (2011): JIFI
Publisher : Fakultas Farmasi Universitas Pancasila

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1963.698 KB)

Abstract

Cancer therapy using chemotherapeutic agents associated with many adversed side effects, including immunosupressant. The use of immunostimulator together with chemotherapeutic agent (co-chemotherapy) can be the alternative method to solve that problem. Ganoderma lucidum (Ling Zhi) has been reported to have immunostimulatory activity. The aim of this research was to evaluate the immunostimulatory activity of water extract of G. Zucidum by determining the relative CD8+ T lymphocyte cell percentage in rats induced by doxorubicin. Extraction of plant material was carried out by infusion method. Sprague Dawley female rats were divided into six groups, they were doxorubicin as control, commercial product as comparing control, 100 mg/kgBW and 450 mg/kgBW extract treatment, extract control, and without treatment control. Relative CD8+ T lymphocyte cell percentages of blood samples were obtained by flow cytometry by using Multiset program. The data were analyzed statistically using paired sample t test and one way ANOVA continued by Post Hoc test. The result showed that the water extract of G. lucidum increased the relative CD8+ T lymphocyte cell percentage in rats induced by doxorubicin. The water extract of G. lucidum is promising to be developed as co-chemotherapy immunostimulatory agent.
Sinergisme Fraksi Butanol Metabolit Sekunder Kapang Endofit 1.3.11 dengan Doxorubicin dalam Modulasi Daur Sel T47D dan MCF-7 SHIRLY KUMALA; EDY MEIYANTO; MUTHI IKAWATI; RIRIS ISTIGHFARI JENIE
JURNAL ILMU KEFARMASIAN INDONESIA Vol 8 No 1 (2010): JIFI
Publisher : Fakultas Farmasi Universitas Pancasila

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1933.007 KB)

Abstract

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.
Efektivitas Hybrid e-Learning Mata Kuliah Kimia Klinik dan Bioanalisis di Fakultas Farmasi, Universitas Gadjah Mada Adam Hermawan; Muthi Ikawati; Susi Ari Kristina; Edy Meiyanto
JURNAL MANAJEMEN DAN PELAYANAN FARMASI (Journal of Management and Pharmacy Practice) Vol 9, No 3
Publisher : Faculty of Pharmacy, Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (702.729 KB) | DOI: 10.22146/jmpf.42718

Abstract

The e-learning method has emerged over the years along with the development of information technology. One of the advantages of this method is not depending on space and time of lecture. The course of clinical chemistry and bioanalysis consisting of lectures and practical courses has time and place limitations for practical and discussion between lecturers and students, therefore learning method innovation is needed. This study aimed to evaluate the effectiveness of the hybrid e-learning method using eLisa on student, as well as understanding and evaluating student perceptions and acceptance of the hybrid e-learning method in clinical chemistry and bioanalysis courses. The platform for the the hybrid e-learning method is eLisa (elisa.ugm.ac.id), developed by the Center for Innovation and Academic Studies (PIKA) UGM. A total of 54 UGM Pharmacy students in the sixth semester of the academic year 2017/2018 participated in this learning activity. Online discussion was conducted on a scientific paper or data obtained from practical courses. Lecturers also provide assignments and online quizzes through eLisa every 2 to 3 weeks. Online assignments and quizzes are opened 24 hours after the lectures. The hybrid e-learning method improve student’s understanding on the lectures and results in the increased number of students who get A marks by 100% compared to conventional learning methods. Most students were satisfied and able to enjoy the learning process with hybrid e-learning with eLisa. This method is able to improve the understanding of subjects and students are satisfied with the implementation of course learning. Further development on improving e-learning methods is needed to improve the quality of learning outcomes.
Co-Authors . Anindyajati Abdul Manaf Ali, Abdul Manaf Adam Hermawan ADTYA FITRIASARI Afifah, Anis Afivah Dewi Anggraeni Agusta Fauzi, Ilham Alfi Yasmina Anindyajati Anindyajati ANINDYAJATI ANINDYAJATI ANNISA KARAMITA Annisa Khumaira Arief Nurrochmad Astrid Ayu Maruti Astrid Ayu Maruti Bayu Anggoro Christina Mutiara Putri Gono Dennaya Kumara Dewi Pratiwi Dewi Pratiwi Dhania Novitasari Dhella Angelina Dhiya Ulhaq Salsabila Dyaningtyas D.P. Putri Dyaningtyas Dewi Putri Pamungkas EDIATI EDIATI Ediati Sasmito Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto EDY MEIYANTO Edy Meiyanto Edy Meiyanto Een Sri Endah Endah Puji Septisetyani Endah Puji Septisetyani, Endah Puji Erlina Rivanti Erlina Rivanti Febri Wulandari Fikri Amalia Gono, Christina Mutiara Putri Hanifa, Mila Hilyatul Fadliyah I Made Rhamandana Ibrahim Arifin Ika Puspitaningrum Ika Putri Nurhayati Ilham Augusta F Ilham Augusta F. Imaniyyati, Niar Nurul Inna Armandari Inna Armandari Irfani Aura Salsabila Jenie, Riris Istighfari Jun-Ya Kato Jun-ya Kato Mintarsih, Betty Mintarsih, Betty Mitsunori Kirihata Moordiani Moordiani Muhammad Novrizal Abdi Sahid Mustofa Mustofa Nanang Fakhrudin, Nanang Nanda Resa Pratama Nanda Resa Pratama Natasia, Nyssa Niken Nur W Niken Nur W, Niken Nindya Budiana Putri Normaidah, Normaidah Novi Hastuti Novi Hastuti, Novi Nurma Sabila Nurramadhani A. Sida Purwanto, Heri Rahmani, Mawardi Rahmani, Mawardi Ratih Hardika Pratama RATIH HARDIKA PRATAMA Ratih Hardika Pratama Ratih Kurnia Wardani Ratna Asmah Susidarti Ratna Asmah Susidarti Ratna Asmah Susidarti Rifai, Fauziah Novita Putri RIRIS ISTIGHFARI JENIE Rita Riata Rita Riata Ritmaleni, Ritmaleni Rohmad Yudi Utomo Sagiyo, Marrita Langgeng Sari Haryanti Sari Haryanti Shirly Kumala Sismindari, Sismindari Sri Handayani Sri Kasianningsih Sri Kasianningsih Sri Pudjiraharti Sukari, Mohd. Aspollah Sukari, Mohd. Aspollah Susi Ari Kristina Susi Ari Kristina Susi Ari Kristina Syifa Athia Zainun Faqiha Tafrihani, Ahmad Syauqy Wulandari Wulandari Yogi Ertanto Yogi Ertanto Yohanes, Jasson Yurista Gilang Yurista Gilang YURISTA GILANG IKHTIARSYAH Ziana Walidah Zulfin, Ummi Maryam