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All Journal Indonesian Journal of Cancer Chemoprevention Majalah Obat Tradisional The Indonesian Biomedical Journal Pharmaceutical Sciences and Research (PSR)
Riris Istighfari Jenie
Fakultas Farmasi, UGM, Sekip Utara Yogyakarta 55281
Biochemistry, Genetics & Molecular Biology Health Professions Medicine & Pharmacology Public Health

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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
Combination of Tangeretin and 5-Fluorouracil Modulates Cell Cycle and Induce Apoptosis on Widr Cells Indriyani, Luthfia; Hermawan, Adam; Jenie, Riris Istighfari
Indonesian Journal of Cancer Chemoprevention Vol 3, No 1 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Co-chemotherapeutics approaches are increasing in cancer treatment in order mainly to suppress the resistance phenomenon of cancer treatment and to enhance the cytotoxic effect of the main chemotherapeutics agent. Tangeretin has been known to have cytotoxic effect to some cancer cells through some pathways in the cells. To explore the potential effect of tangeretin as co-chemotherapeutics agent this research was subjected to study the cytotoxic  effect of tangeretin in combination with 5-Fluoro Uracil (5-FU) on WiDR colon cancer cells covering the modulation of cell cycle and apoptosis induction. Cytotoxic effect was examined by using MTT assay while apoptosis induction was determined by annexin-V flowcytometry. Under MTT assay, tangeretin showed weak cytotoxic activity on the cells. However, tangeretin significantly enhanced the cytotoxic effect of 5-FU on the cells. This co-chemotherapeutics effect likely correlated with cell cycle modulation effect, especially in inducing polyploidy phenomenon as expressed in the flowcytometric graph of the DNA content. This combination also increased apoptosis induction. These result suggest that tangeretin is potential to be developed as co-chemotherapeutic agent for 5-FU on colon cancer and further molecular mechanism need to be exploredKeywords : Tangeretin, 5-Fluorourasil, WiDr, cell cycle, apoptosis
Hesperidin Increases Cytotoxic Effect of 5-Fluorouracil on WiDr Cells Gilang, Yurista; Hermawan, Adam; Fitriasari, Aditya; Jenie, Riris Istighfari
Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Therapy  of  colon  cancer  by  using  5-FU  often  causes  problems  of  resistance.  This encourages the development of co-chemotherapy agent. One of the compounds that could potentially be used as a co-chemotherapy agent  is hesperidin. This study was conducted to determine the cytotoxic effects of hesperidin, 5-FU and the combination of them, as well as apoptosis induction in colon cancer cells WiDr. Cytotoxic effect of hesperidin, 5-FU, and its combination were observed using MTT assay. Observation of apoptosis was done by double staining method using ethidium bromide-acridin orange. Until 48 hours incubation, hesperidin showed no cytotoxic effects. Cytotoxic effects of 5-FU was observed after 48 hours with the IC50 value of 422 µM. However, hesperidin improved the cytotoxic effects of 5-FU at 48 hour incubation.  Either  single  treatment  of  hesperidin  200µM  or  5-FU  1500  µM  did  not  trigger apoptosis, but combination of them led to the emergence of signs of apoptosis. Based on this study,it can be concluded thathesperidin is potential to be developed as a co-chemotherapy agent of 5-FU on colon cancer but still need further study on its molecular mechanisms.Keywords : hesperidin, 5-fluorouracil, WiDr cells, cytotoxic, apoptosis
Aplikasi Ko-Kemoterapi Fraksi Etil Asetat Ekstrak Etanolik Daun Sambung Nyawa (Gynura procumbens (Lour.) Merr.) Pada Sel Kanker Payudara MCF-7 Jenie, Riris Istighfari; Meiyanto, Edy
Majalah Ilmu Kefarmasian Vol. 6, No. 3
Publisher : UI Scholars Hub

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Abstract

Combination chemotherapy has been an interesting attention in recent years to cure cancer e.g. non-toxic or less toxic phytochemicals are being combined with chemo-therapeutic agents to sensitize cancer cell and to enhance the efficacy of chemothera-peutic agents as well as to reduce its toxicity to normal tissues. The aim of this research is to examine whether ethyl acetate fraction of Gynura procumbens ethanolic extract (SEF) synergizes the therapeutic potential of doxorubicin (Dox) on breast cancer cell line MCF-7. MTT assay were used to measure the growth inhibitory effect of the combination therapy on MCF-7 cells. SEF (5-250 µg/ml) treatment of cell resulted in 15-76% growth inhibition in a dose dependent manner (IC50 85 µg/ml), while Dox (10-100 nM) treatment did not show any inhibitory effect. The combina-tions of SEF (5-40µg/ml) with Dox (10-75 nM) seemed to not have any synergistic efficacy towards cell growth inhibition. Nevertheless, this result need further observa-tion regarding the IC50 of Dox on MCF-7 has not been determined yet. The cell characterization may influence the result. Doxorubicin could induce Akt survival apoptosis pathway in MCF-7 resulting resistancy of the cell towards doxorubicin.
Calophyllum inophyllum: A Comprehensive Analysis of its Ethnobotanical, Phytochemical, and Pharmacological Properties Farida, Sofa; Jenie, Riris Istighfari; Fakhrudin, Nanang
Majalah Obat Tradisional Vol 29, No 2 (2024)
Publisher : Faculty of Pharmacy, Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/mot.87488

Abstract

Nyamplung (Calophyllum inophyllum L.) is reported to have ethnomedicinal benefits in traditional medicine systems. Leaves, fruit, seeds, flowers, stems, roots and essential oils are the parts that are often used. Previous scientific studies revealed that this plant part is a valuable resource of secondary metabolites and exhibits a wide range of biological activities. The purpose of this review is to deliver thorough and detailed insights into the traditional uses, chemical ingredients, biology, and pharmacological studies as scientific evidence about the useful efficacy of C. inophyllum in the development of modern medicine. Traditional use shows C. inophyllum is widely used to treat skin diseases, wounds, boils, vaginal discharge, bleeding, gonorrhea, chronic bronchitis, sore eyes, heatstroke, and headaches. C. inophyllum is rich in phenols, polyphenols, flavonoids, xanthones, coumarins, and terpenoids. Several research results show that C. inophyllum possesses a multitude of pharmacological properties including anti-cancer, anti-inflammatory, antimicrobial, antioxidant, antiplatelet, antiviral, and antidiabetic activities.
Pentagamavunon-1 Enhances the Anticancer Effects of Doxorubicin on Triple-Negative Breast Cancer Cells in Monolayers and 3D Cancer Spheroid Models Rahmawati, Desty Restia; Murwanti, Retno; Jenie, Riris Istighfari; Nurrochmad, Arief
The Indonesian Biomedical Journal Vol 17, No 3 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i3.3587

Abstract

BACKGROUND: The 4T1 cells, a triple-negative breast cancer (TNBC) cell line, exhibit high malignancy and metastatic potential. As a primary treatment for TNBC, doxorubicin has limitations, including drug resistance mechanisms and severe side effects such as cardiotoxicity. Pentagamavunone-1 (PGV-1) exhibits antiproliferative and antimetastatic effects, induces prometaphase arrest, triggers cell senescence, and enhances reactive oxygen species (ROS) modulation, which may help overcome doxorubicin resistance. The selective cytotoxicity of PGV-1 against cancer cells suggests that it has a role in reducing systemic toxicity. Therefore, in this study, the anticancer effects of doxorubicin combined with PGV-1 was investigated.METHODS: Monolayer/2D and spheroid/3D models of 4T1 cells were used to assess the effects of PGV-1, doxorubicin, and their combination. MTT assay was used to evaluate the cytotoxicity, colony formation assay was used to measure persistent antiproliferative effects, and spheroid volume analysis was performed to assessed tumor growth inhibition. Senescence-associated beta-galactosidase (SA-β-gal) assay determined cellular senescence.RESULTS: The combination of PGV-1 and doxorubicin significantly enhanced cytotoxicity, with IC50 values of 0.57 µM and 4.88 µM, respectively (p=0.000). A strong synergistic effect was observed, leading to persistent suppression of cancer cell proliferation and an 80% reduction in colony formation (p=0.007). In the 3D spheroid model, combination treatment significantly reduced spheroid volume (p=0.002) more effectively than monotherapy, indicating superior growth inhibition and cytotoxicity. It also increased SA-β-gal, the senescence marker (p=0.010).CONCLUSION: The combination of PGV-1 and doxorubicin demonstrated potent anticancer effects in 4T1 monolayers and spheroid models by enhancing cytotoxicity and inducing cellular senescence. This combination confirmed its potential as a more effective therapeutic strategy.KEYWORDS: 3D spheroid, 4T1 TNBC cell, doxorubicin, pentagamavunon-1, PGV-1, senescence
MMP-9 and TIMP-1 Promote Extracellular Matrix Remodeling in the Formation of Ovarian Endometrioma: in vitro Study on Chicken Chorioallantoic Membrane Sari, Vidia; Jenie, Riris Istighfari; Widad, Shofwal; Dewanto, Agung
The Indonesian Biomedical Journal Vol 15, No 1 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i1.2090

Abstract

BACKGROUND: The invasion of endometrial tissue in the peritoneal layers is an important precursor to the formation of endometriosis. However, the mechanisms of the initial development of endometrioma remain unclear. This study aimed to explore the correlation between matrix metalloproteinase (MMP)-9 activity and tissue inhibitors of metalloproteinase (TIMP)-1 expression in the initial development of endometriosis through the invasion process of endometrial lesions in extracellular matrix (ECM) remodeling.METHODS: A total of 30 samples of endometrioma tissue were obtained from 24 women with endometriosis and examined at Dr. Sardjito General Hospital, Yogyakarta, Indonesia. The tissue was then implanted into a chicken chorioallantoic membrane (CAM) for five days to examine its invasion ability. The invasion scores were assessed using hematoxylin-eosin staining. MMP-9 activity and TIMP-1 expression were analyzed using gelatin zymography and western blot, respectively. The correlations between MMP-9 activity and TIMP-1 expressions with the invasion scores were analyzed using Spearman correlation tests with significance set as p<0.05.RESULTS: The results showed that there was a strong positive correlation between MMP-9 activity and invasion scores of endometriomas tissue (r=0.656; p=0.000). Meanwhile, expression levels of TIMP-1 had a weak negative correlation with the increase of invasion scores of endometrioma (r=-0.388; p=0.034). These results indicate the involvement of MMP-9 and TIMP-1 in the initial development of endometriosis during the ECM remodeling.CONCLUSION: MMP-9 activity and TIMP-1 expression were correlated with the invasion score of endometrioma tissue. This study provides evidence for understanding the mechanisms involved in ECM remodeling in the early process of endometriosis.KEYWORDS: endometrioma, extracellular matrix remodeling, MMP-9, TIMP-1 
Fingerroot (Boesenbergia pandurata) Extract Inhibits Proliferation and Migration of 4T1 Metastatic Breast Cancer Cells Nurrachma, Marsya Yonna; Maran, Gergorius Gena; Putri, Nindya Budiana; Esti, Yuni Fajar; Hermawan, Adam; Meiyanto, Edy; Jenie, Riris Istighfari
Indonesian Journal of Cancer Chemoprevention Vol 11, No 3 (2020)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev11iss3pp103-114

Abstract

Fingerroot (Boesenbergia pandurata) is an Indonesian herb, with anti-proliferation and anti-migratory effects against several cancer cells. This study aims to investigate the anticancer property of Fingerroot Extract (FE) in combination with doxorubicin (Dox) against 4T1, a metastatic breast cancer cell lines. FE was prepared by 96% ethanol maceration and characterized by thin-layer chromatography analysis. FE was subjected to a cytotoxicity test with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay alone or in combination with 10 nM Dox against 4T1 cells. Cytotoxic effect was then confirmed by measure reactive oxygen species (ROS) intracellular level using 2’,7’-dichloroflourescin diacetate (DCFDA)-staining flow cytometry-based assay. The anti-migratory effect was observed using scratch wound healing assay and gelatin zymography to investigate matrix metalloproteinase (MMP)-9 expression. FE showed a cytotoxic effect with an inhibitory concentration 50 (IC50) value of 25.5±3.9 μg/mL and performed an improved effect in combination with 10 nM Dox. A single treatment of FE decreased ROS intracellular level, while in combination with Dox, FE increased the ROS intracellular level. Further, at 42 h observation, FE and its combination with Dox inhibited the migration of 4T1 cells with % closure of 82.6 and 82.5, respectively, correlates with a significant decrease of MMP-9 expression. Overall, FE performs a cytotoxic activity and anti-migration activity on 4T1 breast cancer cells.Keywords: Boesenbergia pandurata, cytotoxic, ROS, anti-migration, 4T1 
Growth Inhibitory Property of Pentagamavunone-0 (PGV-0) on 4T1 Cells under Stress Condition : 2D and 3D Culture Model Muflikhasari, Haruma Anggraini; Jenie, Riris Istighfari; Susidarti, Ratna Asmah; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 10, No 3 (2019)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev10iss3pp149-158

Abstract

Pentagamavunone-0 (PGV-0), one of the curcumin analogue, is reported to have a cytotoxic effect on various cancer cells. This study aimed to explore the growth inhibitory effects of PGV-0 against highly-metastatic breast cancer, 4T1 cells under stress condition covering 2D and 3D speroid cytotoxic, anti-migration, and suppression of MMP-9. PGV-0 showed cytotoxic effects on 2D and 3D 4T1 cells with IC50value of 49 μM and 26 μM, respectively. In addition, PGV-0 performed anti-migratory effect. The single treatment at 25 μM PGV-0 and 50 μM showed inhibitory effect on cell migration by 54% and 51% respectively. whilst, the combination of PGV-0 at the concentration of 25 μM and 50 μM with doxorubicin significantly inhibited cell migration by 41% and 38%,  respectively. The gelatin zymography assay showed that PGV-0 decreased MMP-9 expression both in a single treatment and in combination with doxorubicin. In conclusion,  PGV-0 is potential to be developed as anti-tumorigenesis agent on highly-metastatic breast cancers.Keywords: Pentagamavunone-0 (PGV-0), anti-migration, MMP-9, 4T1 cells, spheroid
Network Pharmacology and In Vitro Validation of Brazilin as a Potential Apoptosis-Inducing Agent in HBV-Related Hepatocellular Carcinoma Hanifa, Mila; Utomo, Rohmad Yudi; Jenie, Riris Istighfari
Indonesian Journal of Cancer Chemoprevention Vol 15, No 3 (2024)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev15iss3pp210-223

Abstract

Hepatitis B virus (HBV) reactivation-related hepatocellular carcinoma (HCC) presents a significant threat due to its potential to cause liver failure and mortality. Consequently, the discovery of novel treatments that offer anticancer efficacy and liver protection is urgently needed. Brazilin, a natural compound, has previously been reported to possess cytotoxic and liver-protective properties. This research aimed to investigate the potency of brazilin in suppressing the growth of HCC cells through in silico and in vitro approaches. Hep3B cells, which harbor integrated HBV DNA, were selected as the HCC model, with PGV- 1 utilized as a positive control. The in silico study used network pharmacology to predict brazilin’s potential gene targets. Cytotoxicity was evaluated using the CCK-8 assay, and apoptosis detection was carried out using Annexin V/PI staining followed by flow cytometry. The analysis predicted that brazilin targets key genes such as SRC, EGFR, AKT1, GRB2, IGF1, ESR1, STAT1, MMP9, JAK2, and PPARG involved in cancer proliferation and metastasis. Proteins such as SRC, GRB2, and MMP9 are overexpressed in TP53-mutated HCC and linked to low survival. Brazilin showed moderate cytotoxicity with an IC50 value of 17 μM at 72 h and significantly induced apoptosis in Hep3B cells. These findings suggest that brazilin is a promising apoptosis-inducing agent for HBV-related HCC.Keywords: brazilin, Hep3B cell lines, network pharmacology, cytotoxic, apoptosis.
Co-Authors Adam Hermawan Aditya Fitriasari Anif Nur Artanti, Anif Nur Arief Nurrochmad Dewanto, Agung Edy Meiyanto Esti, Yuni Fajar Hanifa, Mila Kato, Jun-Ya L. Hartanto Nugroho Luthfia Indriyani Maran, Gergorius Gena Muflikhasari, Haruma Anggraini Nanang Fakhrudin, Nanang Novitasari, Dhania Nurrachma, Marsya Yonna Putri, Nindya Budiana R A Susidarti Rahmawati, Desty Restia Rahmawati, Rahmawati Ratna Asmah Susidarti Retno Murwanti Rohmad Yudi Utomo Rumiyati, Rumiyati Sari, Vidia Shofwal Widad Sofa Farida Sri Handayani Tri Rini Nuringtyas Yurista Gilang Zulkifli Zulkifli