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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) JFIOnline Jurnal Ilmu Kefarmasian Indonesia Majalah Kesehatan Pharmamedika

Muthi Ikawati

Faculty Of Pharmacy, Universitas Gadjah Mada

Author-ID : 285530

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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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

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

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)

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)

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)

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

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.

Curcumin Analogs PGV-1 and CCA-1.1 Induce Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells with Overexpressed MYCN Moordiani Moordiani; Dhania Novitasari; Ratna Asmah Susidarti; Muthi' Ikawati; Jun-ya Kato; Edy Meiyanto
The Indonesian Biomedical Journal Vol 15, No 2 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i2.2147

BACKGROUND: Liver cancer is the third leading mortality in cancer. Curcumin shows effective anticancer potency against various cancer including liver cancer. The synthesized curcumin analog compounds Pentagamavunone-1 (PGV-1) and Chemoprevention Curcumin Analog-1.1 (CCA-1.1) have been well studied in breast, leukemia, and colon cancer cells with better potency than curcumin itself, yet their cytotoxic activities were not known in liver cancer cells. Thus, this study was conducted to elevate the anticancer effect of these curcumin analogs against hepatocellular carcinoma (HCC) cells in vitro, specifically in MYCN-expressing cells, based on its cellular physiology.METHODS: JHH-7 cells were used as the HCC cell model with high expression of MYCN. The viability of the cells was observed using trypan blue exclusion method while cell cycle profile and intracellular reactive oxygen species (ROS) levels were quantified by means of flow cytometry. Chromosomal staining with Hoechst was applied to determine the cell cycle arrest phase, whilst X-gal staining was used to assess the cellular senescence activity.RESULTS: The result of current study presented that the growth inhibitory activity of PGV-1 as well as CCA-1.1 in JHH-7 cells was associated with the cell cycle arrest and cellular senescence. Both curcumin analogs PGV-1 and CCA-1.1 ultimately induced mitotic arrest (p<0.001) better than curcumin. Moreover, PGV-1 and CCA-1.1 similarly increased the senescent cells that partly mediated through ROS elevation. The transcription level of MYCN was not altered upon treatment with curcumin and its analogs in JHH-7 cells, suggesting that molecular mechanism of the inhibitory effect was independent from MYCN signaling.CONCLUSION: Taken together, these observations revealed that both PGV-1 and CCA-1.1 potentially serve as multi-targeted curcumin-based compounds and lead to promising anti-hepatocellular cancer agents.KEYWORDS: Curcumin analogs, hepatocellular carcinoma, mitotic arrest, MYCN

Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47D Rifai, Fauziah Novita Putri; Hanifa, Mila; Zulfin, Ummi Maryam; Ikawati, Muthi; Meiyanto, Edy
Journal of Tropical Biodiversity and Biotechnology Vol 9, No 1 (2024): March
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/jtbb.88238

Pentagamavunone-1 (PGV-1), a curcumin analog, is a promising anticancer candidate for several cancers that have been proven in vitro and in vivo. However, the efficacy of PGV-1 against breast cancer is subject to improvement to achieve a more suitable application. Here we propose hesperitin, a citrus flavonoid, to increase the anticancer potency of PGV-1 in luminal breast cancer cells. We use the T47D cell as the model to investigate the effect of co-administration of PGV-1 and hesperitin on cell cycle block, apoptosis modulation, and senescence phenomena. PGV-1 and hesperitin showed strong and weak cytotoxicity with an IC50 value of 2 µM and 100 µM, respectively. The co-treatment of PGV-1 and hesperitin resulted in strong synergistic effects with combination index (CI) value of ≤ 0.2. This combination caused apoptosis in correlation with cell cycle disruption in G2/M phase at 48 h. In particular, PGV-1 and hesperitin combination increased the incidence of cellular senescence significantly higher than the single treatment. Despite its senescence potentiation, hesperitin did not induce senescence in normal cells. Taken together, hesperitin may increase the anticancer potency of PGV-1 by modulating cell cycle arrest and apoptosis via the senescence mechanism.

Diosmin Enhances the Anti-migration Activity of Curcumin Analog PGV-1 on Colorectal Cancer Cells Ikawati, Muthi; Utomo, Rohmad Yudi; Hapsari, Novia Permata; Meiyanto, Edy; Oka, Chio
The Indonesian Biomedical Journal Vol 16, No 1 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i1.2829

BACKGROUND: Diosmin enhances the cytotoxicity of Pentagamavunone-1 (PGV-1) in cancer cells. PGV-1 and diosmin are predicted to target several matrix metalloproteinases (MMPs) in metastatic cancer, including colorectal cancer, but the anti-migration potency of their combination has not established yet. This study evaluates the anti-migration effect of PGV-1 and diosmin combination in colorectal cancer.METHODS: The cytotoxicity assay using Cell Counting Kit 8 (CCK-8) method in WiDr colorectal cancer cells was carried out to determine the concentration for anti-migration experiments. The wound healing assay was used to observe the anti-migration activity by measuring the cell-free area. Gelatin zymography was employed to detect the MMP activity indicating by the clear band density. The interaction between PGV-1 or diosmin and MMP proteins was predicted by molecular dockings.RESULTS: PGV-1 was cytotoxic (IC50 17 mM), while diosmin up to 100 mM did not affect cell viability. Both 10 mM PGV-1 as well as 50 and 100 mM diosmin slowed down the closure of cell-free area. A 100 mM diosmin was significantly enhance the anti-migratory activity of 50 and 100 mM PGV-1. The activity of MMP-9 and MMP-2 was also lower in the presence of diosmin compared to than that of PGV-1 alone. PGV-1 or diosmin was also able to interact with MMP proteins with a lower energy compared to than that of the native ligands.CONCLUSION: Diosmin enhances the anti-migration activity of PGV-1 in WiDr cells, possibly by affecting MMPs’ activity. This study is an evidence that diosmin is a potential co-chemotherapy candidate for PGV-1, that can be utilized to overcome metastatis in colorectal cancer.KEYWORDS: cancer, citrus flavonoid, co-chemotherapy, diosmin, matrix metalloproteinases (MMPs), migration, Pentagamavunone-1, WiDr cancer cell

Phytochemical and Bioinformatic Studies of Citrus Flavonoids as Chemopreventive Agents Targeting GGPS1 for Liver Cancer Wardani, Ratih Kurnia; Rhamandana, I Made; Gono, Christina Mutiara Putri; Ikawati, Muthi
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/indonesianjcanchemoprev12iss3pp137-147

Overexpression of geranylgeranyl diphosphate synthase 1 (GGPS1) is an unfavorable prognosis in liver cancer development. The side effects of therapeutic standards encourage the development of therapeutic agents from herbal materials. Citrus peels are rich of phytochemical compounds, especially citrus flavonoids, that possess cytotoxic activities. This study aimed to determine the potential of citrus flavonoids as chemopreventive agents targeting GGPS1 protein by phytochemical and bioinformatic studies. Dried peels of Citrus reticulata were extracted by hydrodynamic-cavitation method followed by identification of compounds using thin layer chromatography (TLC). The expression level of GGPS1 was obtained from UALCAN, while its correlation with survival rate was obtained from the GEPIA. Prediction models regarding the potential inhibitors of citrus peel compounds against GGPS1 were obtained through KNIME and ChEMBl, followed by literature studies on chemopreventive activity of citrus flavonoids. The molecular docking was used to predict the molecular interaction followed by tracking of target genes that were positively correlated with GGPS1 by SwissTargetPrediction. Yielded 75% (v/v), the extract positively contained citrus flavonoid with hesperidin as comparison. Overexpression of GGPS1 significantly reduced the survival rate of liver cancer patients (p value=0.019). Four citrus flavonoid compounds, namely tangeretin, nobiletin, hesperidin, and naringenin showed potential inhibition to GGPS1. The molecular docking showed that tangeretin had a strong affinity compared to the native ligand and zoledronic acid, as positive control. PARP1, CSNK2A1, TNKS2, and GSK3B were clarified as targeted genes for tangeretin and nobiletin that positively correlated with GPPS1. In vitro and in vivo studies will validate our findings and support the development of citrus peel extract with rich flavonoid contents as a chemopreventive agent.Keywords: geranylgeranyl diphosphate synthase 1 (GGPS1), liver cancer, hydrodynamic-cavitation, citrus flavonoid, bioinformatic.

Co-Authors . Anindyajati Abdul Manaf Ali, Abdul Manaf Adam Hermawan ADTYA FITRIASARI Afifah Nisa Al Qisthy Afifah, Anis Afivah Dewi Anggraeni Agusta Fauzi, Ilham Alfi Yasmina Angelina, Dhella Anggoro, Bayu ANINDYAJATI ANINDYAJATI Anindyajati Anindyajati ANNISA KARAMITA Annisa Khumaira Astrid Ayu Maruti Astrid Ayu Maruti Aulia Nur Septiani Chio Oka, Chio Dewi Pratiwi Dewi Pratiwi Dhania Novitasari 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 Fatiha Citra Effendi Fikri Amalia Gono, Christina Mutiara Putri Hanifa, Mila Hapsari, Novia Permata Hilyatul Fadliyah Ibrahim Arifin Ika Putri Nurhayati Ilham Augusta F Ilham Augusta F. Imaniyyati, Niar Nurul Inna Armandari Inna Armandari Jenie, Riris Istighfari Jun-ya Kato Jun-Ya Kato Kumara, Dennaya Mintarsih, Betty Mintarsih, Betty Mitsunori Kirihata Moordiani Moordiani Muhammad Novrizal Abdi Sahid Muhammad Yusuf Alfaqih Mustofa Mustofa Nadya Rianasari 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 Putri, Amaliya Permata Rahman, Faaza Aulia Rahmani, Mawardi Rahmani, Mawardi Rahmawati, Desty Restia RATIH HARDIKA PRATAMA Ratih Hardika Pratama Ratih Hardika Pratama Ratna Asmah Susidarti Ratna Asmah Susidarti Ratna Asmah Susidarti Rhamandana, I Made 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 Wardani, Ratih Kurnia Wulandari Wulandari Wulandari, Febri Yogi Ertanto Yogi Ertanto Yohanes, Jasson Yurista Gilang Yurista Gilang YURISTA GILANG IKHTIARSYAH Ziana Walidah Zulfin, Ummi Maryam

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