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All Journal HAYATI Journal of Biosciences Indonesian Journal of Cancer Chemoprevention Indonesian Journal of Biotechnology INDONESIAN JOURNAL OF PHARMACY The Indonesian Biomedical Journal
Jenie, Riris Istighfari
Cancer Chemoprevention Research Center, Faculty Of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara Sleman, Yogyakarta 55281
Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Earth & Planetary Sciences Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology Public Health

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Cytotoxic and Antimetastasis Effect of Ethyl Acetate Fraction from Caesalpinia sappan L. on MCF-7/HER2 Cells Riris Istighfari Jenie; Sri Handayani; Ratna Asmah Susidarti; Zalinar Udin; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 8, No 1 (2017)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev8iss1pp42-50

Abstract

Overexpression of HER2 in breast cancer cell is found on invasive breast cancer and correlated with worse prognosis. Caesalpinia sappan L shows cytotoxic activity on various cancer cells. The goal of this research is to determine the cytotoxic activity and inhibition of migration and invasion of ethyl acetate fraction of Caesalpinia sappan L. (FEA) on HER2 overexpression-breast cancer cells (MCF-7/HER2). The MTT and flow cytometry assay showed that FEA revealed cytotoxic effect in a dose-dependent manner (IC50= 34 ± 3.1 µg/ml) and induced apoptosis, S and G2/M phase accumulation. Wound healing assay, gelatin zymography and immunoblotting assay showed that FEA inhibited migration and suppressed MMP2, MMP9, HER2 and Rac1 protein level. Thus, ethyl acetate fraction of Caesalpinia sappan L. is potential to be developed on future research especially to treat metastatic breast cancer with HER2 overexpression.Keywords: Ethyl acetate fraction of Caesalpinia sappan L, cytotoxic effect, migration and invasion, MCF-7/HER2 cells
The Safety of Areca Seed Ethanolic Extract as Potential Chemopreventive Agent is Proven by Acute Toxicity Test Sri Handayani; Riris Istighfari Jenie; Ratna Asmah Susidarti
Indonesian Journal of Cancer Chemoprevention Vol 3, No 1 (2012)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev3iss1pp345-350

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 (Rattus 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 groups 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 shows the safety of areca seed ethanolic extract which is important for its development as chemopreventive agent.Keywords: Areca catechu, acute toxicity, rat
Anti-Aging Activity Of Cucurbita moschata Ethanolic Extract Towards NIH3T3 Fibroblast Cells Induced By Doxorubicin Laeli Muntafiah; Bani Adlina Shabrina; Dwi Sulistyowati; Murah Riski Novi Asshagab; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 7, No 2 (2016)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev7iss2pp49-53

Abstract

Degenerative disease caused by decreasing organ function in old people has become the biggest death cause in the world. This aging process marked by senescence activity. An anti-aging agent from the medicinal plant has high potency to be developed, such as pumpkin seed (Cucurbita moschata) which contain tocopherol as antioxidant. The aim of this study is to investigate the anti-aging effect of pumpkin seed extract (PSE) on NIH 3T3 fibroblast normal cell induced by doxorubicin. This anti-aging effect was observed using MTT assay continued by SA- βgal (Senescence-Associated Beta-Galactosidase) activity detection test. The stability of  molecular interaction between tocopherol and doxorubicin to CYP 3A4 as the oxidase enzyme was conducted using molecular docking. Based on in vitro test, PSE is not cytotoxic to NIH 3T3. PSE at the dose of 100,200,400, and 800 μg/mL decreased % cell senescence by 2,77; 4,5; 6; and 18 times respectively. Meanwhile, in silico test indicated that tocopherol (-107,409) has a higher interaction to CYP 3A4 compared to doxorubicin (-70,52). Both compounds have a similar binding site in Leu 364; Phe 435; Pro 434; Cys 442; Ile 369; Thr 309; dan Ala 305. The overall result of this study showed that PSE has anti-aging effect by decreasing SA- βgal activity. This anti-aging activity possibly due to the interaction between tocopherol to CYP 3A4 based on molecular docking.Keywords: anti-aging, Cucurbita moschata, tocopherol, SA-βgal, molecular docking
Ethanolic Extract of Hedyotis corymbosa and Its Combination with 5-FU Inhibit Cyclin D Expression on WiDr Colorectal Cancer Cell Argandita Meiftasari; Januar Caesar W.P.; Annisa Novarina; Julika Yovi W.; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 7, No 1 (2016)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev7iss1pp25-30

Abstract

Hedyotis corymbosa has been used for long time as an important component in several folklore medicine formula to clinically treat various types of cancer, including colorectal cancer (CRC). Previously, Hedyotis corymbosa ethanolic extract (HEE) which contain ursolic acid reported to inhibit CRC growth via induction of cancer cell apop­tosis and blocked the cell cycle, preventing G1 to S progression where cyclin D highly espressed in this phase. 5-fluorouracil (5FU), the first line chemotherapy of colorectal cancer have had resistence and possessed several side effects such as neutropenia, immunosuppression, diarrhea, and also constipation. Therefore, the aim of this research is to conduct the antiproliferative effect and molecular analysis of HEE and its combination with 5FU. Molecular docking study was also done to approach the specific protein target of the compound. Antiproliferative effect was conducted by MTT assay, while cyclin D expression  was examined by immunofluorescence. The proliferative effect showed that both HEE and 5-FU had cytotoxic effect with IC50 value of 65 µg/mL and 90 µM respectively, meanwhile the combination of HEE and 5FU have synergism effect with CI = 0.48 on dose HEE = 22 µg/mL and 5FU= 6.25 µM. Immunofluorescence assay showed HEE and its combination with 5FU suppressed the expression of cyclin D. From molecular docking simulation, ursolic acid performed stable interaction with cyclin D. Our findings suggest that HEE may be an effective treat­ment for co-chemotherapic for 5-FU through inhibition of cyclin D expression.Keywords : Hedyotis corymbosa, 5-fluorouracil, colorectal cancer,  WiDr, cyclin D 
Ethanolic Extract of Secang Heartwood (Caesalpinia sappan L.) Increases Bone Density in Ovariectomized Rats Bani Adlina Shabrina; Nita Kristiani; Khairunisa Irnanda; Fajar Aji Lumakso; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 4, No 1 (2013)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev4iss1pp477-482

Abstract

Osteoporosis has become a major public health concern, due to its rising incidence every year. Osteoporosis mostly occurs in women at menopause, especially in Asia. Secang (Caesalpinia sappan L.) heartwood contains brazilin and brazilein which are known to suppress expression of NF-ĸB, an osteoclastogenesis protein playing an important role in osteoporosis.  Thus, the aim of this research is to investigate the inhibition of osteoporosis by ethanolic extract of secang (Caesalpinia sappan L.) (EES) in ovariectomized (OVX) rats. Thirty female Sprague Dawley rats were divided into five groups treated for 20 days:  group I were OVX and treated with 1000 mg/kgBW EES; group II were OVX and treated with 500 mg/kgBW EES; group III were OVX and treated with CMC-Na; group IV were shame OVX baseline; and group V were non-OVX-baseline. Bone density was examined by using X-Ray rontgen and was strengthen by qualitative data of Giemsa staining. Moreover, total number of osteoclasts in bone slide was observed by TRAP expression using double staining immunohistochemistry with hematoxylin eosin (HE) – TRAP. Treatment of 500 mg/kgBW EES in ovariectomized rats showed the highest bone density of 0.60 gr/cm3 and the lowest number of osteoclasts was 4.66 osteoclasts per field of view. These results showed that EES is potent to be developed as an antiosteoporosis agent. Further study on its dose adjustment and molecular mechanism needs to be conducted.Keywords: Caesalpinia sappan L., osteoporosis, RANK, bone density
Antiproliferative Effect of Secang Heartwood Ethanolic Extract (Caesalpinia sappan L.) on HER2-Positive Breast Cancer Cells Rahmawaty Rachmady; Laely Muntafiah; Fahmi Rosyadi; Imroatus Sholihah; Sri Handayani; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 7, No 1 (2016)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev7iss1pp1-5

Abstract

Human Epidermal Growth Factor Receptor 2 (HER2) plays critical role in the initiation of breast cancer cell proliferation. Inhibition of HER2 overexpression is a promising strategy in the treatment of breast cancer. One of the potential natural substances that possess cytotoxic in cancer cells is Secang (Caesalpinia sappan L.). Ethanolic extract of secang heartwood containing brazilein and brazilin shows cytotoxic effect on various cancer cells. Thus this research aims to determine the proliferative inhibition activity of secang heartwood ethanolic extract (SEE) through HER2 expression on MCF-7/HER2 positive. Cytotoxic activity of SEE on MCF-7/HER2 positive cells was observed by MTT assay, meanwhile the inhibition activity of  HER2 on MCF-7/HER2 cells was determined by immunofluoresence assay. Furthermore, to confirm the possible mechanism of brazilein and brazilin for its cytotoxic activity was studied through molecular docking using PLANTS software. Based on this study, SEE exhibited cytotoxic effect on MCF-7/HER2 positive cells with IC50 value of 25 µg/ml, and EES also inhibited HER2 expression, indicated that the antiproliferative effect of SEE was possible through the inhibition of HER2. Docking score of brazilein, brazilin, and native ligand on HER2 were -77; -73; -120 respectively, showed the affinity of brazilein in HER2 was lower than affinity of native ligand, but they had specific amino acid to interaction. Hence, SEE can be developed as one of promising chemopreventive agent from natural products.Keywords: Caesalpinia sappan L., cytotoxic, immunofluorescence, molecular docking, MCF7/HER2 cells
Jure Leaf Extract (Nerium indium Mill.) Increased 5-Fluorouracil Sensitivity through Inhibition of NF-κB Activation and Transporter Protein in WiDr Colon Cancer Cell Imroatus Sholihah; Meirizky Zulharini S.; Amalia Miranda; Refki Riswansyah; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 7, No 3 (2016)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev7iss3pp87-92

Abstract

5-Fluorouracil (5-FU) is the first line chemotherapeutic agents for colon cancer therapy. Long term used of 5-FU caused cancer cell resistency. Thus, co-chemoteraputics agent should be developed to increase cells sensitivty towards 5-FU. Jure leaf  (Nerium indicum Mill) extract (JLE) contains oleandrin which has cytotoxic effect on colon cancer cell. The ain of this study was to investigated the mechanism of JLE to sensitized colon cancer cell toward 5-FU through NF-κB inhibition and MRP protein repression. JLE was extracted by soxhletation method. Based on molecular docking to MRP protein, docking score of oleandrin (-50,496)  was higher than native ligand ATP (-125,817). Oleandrin could interfere interaction with MRP. JLE increased 5-FU sensitivity a dose of 2 µg/mL JLE dan 12,5 µM 5-FU with the combination index (CI) of  0,594. Combination of JLE and 5-FU also inhibit p65 protein expression on WiDr cell.Keywords: cytotoxic, Nerium indicum Mill., oleandrin, immunofluorescence, molecular docking
Methanolic Extract of Red Betel Leaves (Piper crocatum Ruiz & Pav) Perform Cytotoxic Effect and Antimigration Activity toward Metastatic Breast Cancer Meirizky Zulharini; Ika Rahmawati Sutejo; Hilyatul Fadliyah; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 8, No 3 (2017)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev8iss3pp94-100

Abstract

Breast cancer is one type of cancer with a high mortality rate due to its metastatic property. Red betel leaves (Piper crocatum Ruiz and Pav) has been known as herbal medicine containing biophenolic, such as apigenin and luteolin derivatives which has cytotoxic activity toward cancer cells. This study is intended to explore the inhibitory effect of Piper crocatum leaves methanolic extract (PCM) on cell proliferation and migration by using 4T1 cells as model of metastatic breast cancer. By using MTT assay, PCM performed cytotoxic activity in a dose dependent manner with IC50 value of 120 μg/mL. Wound healing assay revealed that migration inhibitory activity of PCM on 4T1 cells at the concentration of 30 µg/mL. In conclusion, PCM perform cytotoxic effect and antimigration activity toward metastatic breast cancer cells.Keywords : breast cancer cells, Piper crocatum Ruiz & Pav, cytotoxic, cell mgration
Co-Authors Adam Hermawan Akhmad Darmawan Amalia Miranda Amalia Miranda Annisa Novarina Argandita Meiftasari Bani Adlina Shabrina Bani Adlina Shabrina Devi Nisa Hidayati Diah Tri Utami Dwi Sulistyowati Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Een Sri Endah Fahmi Rosyadi Fajar Aji Lumakso Hilyatul Fadliyah Ika Rahmawati Sutejo Imroatus Sholihah Januar Caesar W.P. Julika Yovi W. Khairunisa Irnanda Laeli Muntafiah Laely Muntafiah Laili Nailul Muna Lina Permatasari Luthfia Indriyani Meirizky Zulharini Meirizky Zulharini S. Meirizky Zulharini S. Murah Riski Novi Asshagab Muthi Ikawati Nadzifa Nugraheni Nita Kristiani Prisnu Tirtanirmala Puspa Dewi Narrij Lotulung Rahmawaty Rachmady Raisatun Nisa Sugiyanto Ratna Asmah Susidarti Ratna Asmah Susidarti Refki Riswansyah Retno Murwanti Rohmad Yudi Utomo Rumiyati Rumiyati Sri Handayani Sri Handayani Sri Handayani Sri Handayani Sri Handayani Sri Handayani Sri Pudjiraharti Yogi Ertanto Zalinar Udin Zalinar Udin