Jenie, Riris Istighfari
Cancer Chemoprevention Research Center, Faculty Of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara Sleman, Yogyakarta 55281

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Antimigratory Activity of Brazilin-Containing Fraction from Caesalpinia sappan L. on MDAMB-231 Cells Sri Handayani; Ratna Asmah Susidarti; Puspa Dewi Narrij Lotulung; Akhmad Darmawan; Edy Meiyanto; Riris Istighfari Jenie
HAYATI Journal of Biosciences Vol. 27 No. 4 (2020): October 2020
Publisher : Bogor Agricultural University, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.4308/hjb.27.4.266

Abstract

Caesalpinia sappan is studied for several biological activities. The aim of this research is to determine the cytotoxic and antimigratory activities of Caesalpinia sappan active fraction in combination with cisplatin on human TNBC cells (MDA-MB-231). Caesalpinia sappan heartwood was extracted with methanol. Then, several fractions of the methanol extract were obtained by using a liquid-liquid extraction method followed by column chromatography. The cytotoxicity was determined using MTT assay. Synergistic effects were analyzed by calculating the combination index (CI). Migration was examined using wound-healing assay. Levels of MMP2 activity were determined with gelatin zymography assay. The results showed that most of the fractions included in this study exhibited cytotoxic effects against MDA-MB-231 cells, and C fraction demonstrated the highest cytotoxic activity of all fractions. The combination of C-cisplatin revealed a synergistic inhibitory effect on MDA-MB-231 cell growth (CI<1). Furthermore, C fraction, alone and in combination with cisplatin, inhibited migration of MDA-MB-231 and suppressed MMP2 activity. The C fraction isolated from Caesalpinia sappan increased the cytotoxic and antimigratory activities of cisplatin on MDA-MB-231 cells. Based on these findings, the potential of Caesalpinia sappan to act as a supportive agent in metastatic TNBC treatment with cisplatin warrants further exploration.
Brazilein in combination with cisplatin inhibit proliferation and migration on highly metastatic cancer cells, 4T1 Sri Handayani; Ratna Asmah Susidarti; Zalinar Udin; Edy Meiyanto; Riris Istighfari Jenie
Indonesian Journal of Biotechnology Vol 21, No 1 (2016)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1342.29 KB) | DOI: 10.22146/ijbiotech.26106

Abstract

Brazilein performs anti­cancer activities on several cancer cells and potentially inhibits metastasis. The aims of this study is to observe the synergistic cytotoxic and migration inhibitory effect of brazilein combined with cisplatin on 4T1 breast cancer cells. Under MTT assay, we found that brazilein revealed cytotoxic effect on 4T1 cells in a dose­dependent manner (IC50=50 ± 0.3 µM). Combination of brazilein and cisplatin showed synergistic effect (CI=0.72). Flowcytometry analysis on the cell cycle progression showed that single treatment of 25 µM brazilein induced G2/M­phase accumulation, 12.5 µM cisplatin induced S­phase accumulation, while combination of brazilein and cisplatin induced S­phase and G2/Mphase accumulation. Combination of brazilein and cisplatin induced apoptosis higher than that of the single treatments. Based on wound healing assay, 12.5 µM brazilein and its combination with 6.25 µM cisplatin inhibited cells migration. Immunoblotting and gelatin zymography analysis showed that combination of brazilein and cisplatin inhibited the expression level of Rac1 and MMP9 proteins. Based on these results, we conclude that brazilein enhanced cytotoxic activity of cisplatin and inhibited migration on 4T1 cells and potentially can be developed as an enhancing cytotoxic and antimetastasis agent.
Snake beans (Vigna sinensis (L) Savi ex Hassk) extract increases breast epithelial cells proliferation Edy Meiyanto; Sri Handayani; Riris Istighfari Jenie
Indonesian Journal of Pharmacy Vol 19 No 4, 2008
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1596.989 KB) | DOI: 10.14499/indonesianjpharm0iss0pp191-197

Abstract

Some Javaness people use snake beans for skin and breast care, especially for better breast development. This research was conducted to examine the effect of snake beans extract (EKP) on the breast epithelial cells proliferation on in vitro and in vivo models. The in vitro experiment was carried out against MCF-7 cells using MTT assay and morphologically examination was carried out under light microscope. Sprague Dawley female Rats were used in in vivo experiment. The rats (30 days of age) were separated into 3 groups, namely base line group, control group, and treatment groups. The extract was administered in the dose of 1000 mg/kgBW p.o. every day for 14 days then the rats were examined for wet uterus weight, lobulus development, and estrogen receptor (ER) expression. Extract treatment induced MCF-7 cells proliferation in dose dependent manner. The extract exhibited proliferative effect in the dose of 50 ug/mL 300 ug/mL, but in the dose of 400 ug/mL and 500 ug/mL the extract inhibited cells proliferation and there were no cell death effect. Extract treatment in the dose of 1000 mg/kgBW tended to increase uterus weight. The extract also increased lobulus development up to two fold and induced estrogen receptor expression in epithelial cells of lobulus and ductus. These results conclude, snake bean (in appropriate dose) induces breast glands development and relatively safe (no death effect on the cells), therefore can be developed for breast care product.Key words: Snake bean, breast care, proliferation, lobulus epithelial cells, estrogen receptor
Antiangiogenic effect of sambung nyawa leaves (Gynura procumbens (Lour.) Merr.) etanolic extract on chick embryo chorioallantoic membrane (CAM) Riris Istighfari Jenie; Edy Meiyanto; Retno Murwanti
Indonesian Journal of Pharmacy Vol 17 No 1, 2006
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (411.767 KB) | DOI: 10.14499/indonesianjpharm0iss0pp50-55

Abstract

Antiangiogenesis (inhibition of new blood vessels formation) has become a strategy to inhibit cancer development lack of nutrition and oxygen supply. The aim of the present research is to investigate antiangiogenesis effect of ethanolic extract of Gynura procumbens (Lour.) Merr. Leaves in situ using chick embryo chorioallantoic membrane (CAM). Eight to 9 days old fertilized chicken eggs were treated with b-FGF (angiogenesis inductor) and extracts. Eggs were then incubated for 3 days in order to observe its angiogenesis response (new blood vessels converged toward the implant).The results showed that the ethanolic extract of G.procumbens could inhibit angiogenesis in a dose-dependent manner. Doses 10, 20, 40, 80 ug gave angiogenesis response of (in percent) 82.32 ± 6.33; 68.38 ± 6.24; 56.48 ± 11.61; 41.43 ± 7.46 (p<0.05), respectively. These results indicate a potential antiangiogenic effect of the extract.Key words: antiangiogenic, CAM, G.procumbens.
Anti-Osteoporosis Potencies of Zingiber officinale Rosc. Rhizome Water Extract and DFA III Produced from Dahlia spp. L.: in vivo and in vitro Studies Muthi’ Ikawati; Yogi Ertanto; Een Sri Endah; Sri Pudjiraharti; Edy Meiyanto; Riris Istighfari Jenie
The Indonesian Biomedical Journal Vol 14, No 1 (2022)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v14i1.1787

Abstract

BACKGROUND: Zingiber officinale Rosc. is estrogenic and thus can be developed as an anti-osteoporosis. Difructose anhydride III (DFA III), possesses anti-osteoporosis potencies. This study aimed to investigate the anti-osteoporosis activity of ginger rhizome water extract (GE) and DFA III from dahlia tubers in ovariectomized (OVX) rat models and to determine their anti-osteoclastogenic effect in vitro.METHODS: This study was conducted using 25 female rats. Blood sampling was carried out at the beginning and end of treatments. Femur bones were isolated after daily 14-day treatments, measured for density, and processed for histological staining. RAW 264.7 cells were induced by osteoclast differentiation factor. A cell viability assay was employed to determine the cytotoxicity of DFA III and GE. The inhibition of osteoclastogenesis was investigated by tartrate-resistant acid phosphatase staining.RESULTS: All groups showed no difference in body weight elevation and serum lipid profiles. The GE and DFA III caused no effect on bone density. However, the GE or DFA III groups showed higher osteoblast numbers compared with the control groups. A significantly less osteoclast was found in the GE+DFA III group. The GE and DFA III showed no toxicity on RAW 264.7 cells. GE showed strong inhibitory effects on the post stimulation osteoclastogenesis model. The combination of GE and DFA III was synergistic in reducing the osteoclastogenesis confluency in RAW 264.7 cells.CONCLUSION: The data support our hypothesis that GE and DFA III can decrease the risk of osteoporosis by osteoclastogenesis inhibition.KEYWORDS: Dahlia spp., estrogenic, ginger, osteoclast, osteoporosis, ovariectomy, RAW 264.7 cell
Co-treatment of Brazilein Enhances Cytotoxicity of Doxorubicin on WiDr Colorectal Cancer Cells Through Cell Cycle Arrest Diah Tri Utami; Nadzifa Nugraheni; Riris Istighfari Jenie; Edy Meiyanto
The Indonesian Biomedical Journal Vol 12, No 4 (2020)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v12i4.1293

Abstract

BACKGROUND: The presence of adverse side effects limits the use of doxorubicin (Dox) despite its cost-effectiveness compared to other chemotherapeutic agents. Brazilein (Be), the major compound of Caesalpinia sappan, performs co-chemotherapeutic potency in several cancer cell lines. This study evaluates the chemosensitizing effects of Be to Dox on colon cancer cell line, WiDr.METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted to evaluate the cytotoxic effect of Be and its combination with Dox. The synergistic effect of Be and Dox was examined by using the Combination index (CI) parameter. Cell cycle and apoptosis profiles were done using flow cytometry with propidium iodide (PI)/RNase and Annexin V staining, respectively.RESULTS: The combination of Dox and Be at half of IC50 on WiDr cells showed a synergistic effect with a combination index of 0.4. Analysis of the cell cycle revealed that the combination caused cell cycle termination at the S and G2/M phase. This finding corresponded with the data that single treatment of Dox and Be induced cell cycle arrest at the different phases, namely S and G2/M phase, respectively. However, the combination treatment for 24 hours did not induce apoptosis. This combination should be further clarified as there was a possibility that many cells may underwent permanently arrest that halts to proceed apoptosis.CONCLUSION: Our findings suggested that Be synergizes with Dox to suppress the growth of WiDr cells via cell cycle arrest, hence, Be is potential to be developed as a co-chemotherapeutic agent. Our findings suggested that Be synergizes with Dox to suppress the growth of WiDr cells via cell cycle arrest, hence, Be is potential to be developed as a co-chemotherapeutic agent.KEYWORDS: Brazilein, colon cancer WiDr, co-treatment, Doxorubicin, cell cycle arrest
Cytotoxic and Apoptotic-inducing Effect of Fraction Containing Brazilein from Caesalpinia sappan L. and Cisplatin on T47D Cell Lines Prisnu Tirtanirmala; Annisa Novarina; Rohmad Yudi Utomo; Raisatun Nisa Sugiyanto; Riris Istighfari Jenie; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 6, No 3 (2015)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev6iss3pp89-96

Abstract

Anticancer activity of secang’s heartwood (Caesalpinia sappan L.) is based on its main compound: brazilin and brazilein. Brazilin, brazilein, and other compounds such as caesalpiniaphenol can affect proteins that have a role in apoptosis. In this study, we observed cytotoxic activity of fraction containing brazilein (FCB) alone or in combination with chemotherapeutic agent, cisplatin and the ability of the combination to induce apoptosis in T47D breast cancer cell lines. Cytotoxicity assay was determined using MTT assay, whereas the detection apoptosis induction was conducted using flow cytometry using Annexin-V and propidium iodide. FCB and cisplatin showed cytotoxic effect on T47D cells with IC50 value of 68 µg/mL and 16 µM, respectively. Combination of FCB and cisplatin result synergistic combination at the concentration ratio of 1/2 IC50 with CI value of 0.66. Its combination also able to induce apoptosis on T47D cell population 13% larger than the single treatment. Based on this study, we conclude that FCB is able to enhance the cytotoxic effects of cisplatin by inducing apoptosis.Keywords:  Caesalpinia sappan L., cisplatin, apoptosis, breast cancer
Phaleria macrocarpa Fruit Extract Inhibits NF-ĸB Activation and Apoptosis Induction on HeLa Cells Meirizky Zulharini S.; Amalia Miranda; Lina Permatasari; Hilyatul Fadliyah; Riris Istighfari Jenie
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/indonesianjcanchemoprev8iss1pp9-14

Abstract

NF-κB is a transcription factor and if activated, it induces apoptosis inhibition. Phalerin from Phaleria macrocarpa fruits expected to inhibit NF-κB activation. This research is to investigate anticancer mechanism of Phaleria macrocarpa fruits extracts (EBMD) in NF-κB pathway. Molecular docking assay was performed to determine phalerin affinity to IKK. Cytotoxic activity was observed by MTT assay. Double staining was performed to determine the apoptotic cells. Docking score of phalerin to IKK is -60. The IC50 value of EBMD is 629 μg/mL. Apoptosis profile shows (shown that) many cells undergoing apoptosis after treatment. Thus, EBMD potentially inhibits activation of NF-κB pathway and triggers apoptosis on HeLa cells.Keywords : NF-κB, Phaleria macrocarpa, sel HeLa, Bcl-2, IKK, molecular docking
Combination of Tangeretin and 5-Fluorouracil Modulates Cell Cycle and Induce Apoptosis on WiDr Cells Luthfia Indriyani; Adam Hermawan; Riris Istighfari Jenie
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/indonesianjcanchemoprev3iss1pp364-369

Abstract

Co-chemotherapeutics approaches are increasing in cancer treatment in order mainly to suppress the resistence 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 apoptotis 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 explored.Keywords: Tangeretin, 5-Fluorourasil, WiDr, cell cycle, apoptosis.
Acute Toxicity and Genotoxic Activity of Leunca (Solanum nigrum L.) Herb Ethanolic Extract Rumiyati Rumiyati; Laili Nailul Muna; Devi Nisa Hidayati; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 6, No 1 (2015)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev6iss1pp30-34

Abstract

Previous studies showed that Leunca herb ethanolic extract (LHE) has cytotoxic activity in several cancer cell lines such as HepG2 and HT-29. The extract also demonstrated as potential agent to be developed as co-chemotherapeutic in combination with doxorubicin and cisplatin. The combination is supposed to reduce occurance of cell resistance and  toxicity towards normal cell. In order to verify safety before being applied to human, toxicological and genotoxic evaluation of the extract is important to be done. This research was therefore aimed to investigate acute toxicity and genotoxic activity of LHE. The acute toxicity study was carried out in three groups of 5 mice that was orally administrated by LHE at different doses consisting 300, 2000 and 5000 mg/kgBW. Mortality and sign of toxicity were observed during 7 days. Genotoxic activity was carried out using Mononuclear Polychromatic Erythrosite (MNPCE) assay at a doses range of 250, 500, and 1000 mg/kgBW. Cyclophosphamide (CYP) at the dose of 50 mg/kg was used as positive control. The result showed that LHE did not cause lethal effect on animal model up to doses of 5000 mg/kgBW. However, toxicity signs were found in animal model on day 0-6 of the observation. LHE had lower genotoxic activity compared to cyclophosphamide at the doses of 250, 500, and 1000 mg/kg. The low genotoxic activity and acute toxicity of LHE suggested that the extract might be safe to be used as medicine.Keywords: leunca herb ethanolic extract, genotoxicity, acute toxicity