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All Journal Indonesian Journal of Cancer Chemoprevention Journal of Mathematical and Fundamental Sciences Indonesian Journal of Biotechnology Majalah Farmaseutik Jurnal Ilmu Kefarmasian Indonesia
Ratna Asmah Susidarti
Cancer Chemoprevention Research Center, Faculty Of Pharmacy, Universitas Gadjah Mada
Astronomy Biochemistry, Genetics & Molecular Biology Chemistry Earth & Planetary Sciences Health Professions Immunology & microbiology Materials Science & Nanotechnology Mathematics Medicine & Pharmacology Physics Public Health

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Ethanolic Extract of Papaya (Carica papaya) Leaves Improves Blood Cholesterol Profiles and Bone Density in Ovariectomized Rats Raisatun Nisa Sugiyanto; Rahmi Khamsita; Ratna Asmah Susidarti
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/indonesianjcanchemoprev3iss3pp426-431

Abstract

Bone loss and disturbance in the blood cholesterol profiles modulation are two effects caused by menopauses syndromes. As the estrogen concentration in the body decreased drastically, menopause women need the replacement of estrogen to keep the regulation of several physiological functions in the body, such as bone generation and cholesterol regulation in a good condition. Phytoestrogen in Carica papaya leaves, such as quercetin, could be one of the potential agents for the estrogenic effect. The aim of this study is to know the effects of papaya leaf extract (PLE) on the blood cholesterol profiles and bone density in ovariectomized rats. Thirty six female Sprague Dawley rats divided into six groups.  The groups were sham-treated ovx (S-OVX), ovariectomized rats (OVX), CMC-Na control (OVX+CMC-Na), positive control (OVX+Estradiol), and the PLE treatment groups dose 750 mg/kgBW (OVX+750mg/kgBW) and dose 1000 mg/kgBW (OVX+1000 mg/kgBW). Administrations of PLE were done in three weeks orally and estradiol administrated intraperitonially. In the end of the treatment, the blood sample of tested animals was collected for the blood cholesterol determination (LDL, HDL, triglyceride, and total cholesterol) and the femur bones were examined for the bone density. Based on the results, PLE dose of 750 mg/kgBW a day in ovariectomized rats showed estrogenic effects in modulating blood cholesterol profile by lowering total cholesterol levels. Meanwhile, PLE dose of 1000 mg/kgBW significantly increased the bone density (p<0.05). Thus, PLE is potential to overcome the negative effects of post-menstrual women especially in the cholesterol blood profiles and bone density.Keywords : Carica papaya, phytoestrogen, bone density, blood cholesterol, ovariectomized rats
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
Hesperidin Increase Cytotoxic Activity of Doxorubicin on Hela Cell Line Through Cell Cycle Modulation and Apoptotis Induction Indri Kusharyanti; Larasati Larasati; Ratna Asmah Susidarti; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 2, No 2 (2011)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev2iss2pp267-273

Abstract

Combination of chemotherapeutic agent and chemopreventive agent is being a new approach in cancer treatment. This is aimed at enhancing the effectivity and also reducing drug resistance and adverse side effect of the chemotherapeutic agent. Hesperidin, a citrus flavonoid has reported to reduce the proliferation of many cancer cells. The objectives of this study were to investigate cytotoxic activities, cell cycle modulation and apoptosis induction of hesperidin and its combination with doxorubicin on Hela cell lines. MTT [3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide] assay was used to measure the growth inhibitory effect of hesperidin and its combination with doxorubicin on Hela cells. Cell cycle profile was determined by flowcytometry and the data obtained was analyzed by using ModFit LT 3.0 program. Apoptosis assay was done using double staining method using ethidium-bromide and acridine-orange. Hesperidin inhibited cell growth with IC50 48 μM, while the IC50 of doxorubicin was 1000 nM. Combination of 500 nM doxorubicin and 6 μM hesperidin showed strongest inhibitory effect toward Hela cells. Hesperidin of 24 µM accumulated HeLa cells at G1 phase, but its combination with 500 nM Doxorubicin gave G1 and S phase accumulation at 24 h incubation. Both of Hesperidin and Doxorubicin were capable of inducing apoptosis. In accordance of the apoptotic effect, hesperidin, doxorubicin and their combination decreased the expression Bcl-2 and increased the expression of Bax. According to this result, hesperidin has a potency to be developed as co-chemotherapeutic agent for cervical cancer.Keywords: Cochemotherapy, Hesperidin, Doxorubicin, Hela, MTT assay
Cinnamomum Essential Oil Prevents DNA Damage-Induced by Doxorubicin on CHO-K1 Cells Layung Sekar Sih Wikanthi; Nindi Wulandari; Yuni Fajar Esti; Nur Fitra Sari; Ratna Asmah Susidarti
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/indonesianjcanchemoprev8iss1pp27-31

Abstract

DNA damage usually happens due to the several chemical materials that induce genotoxic effect in normal cells. Cinnamon essential oil (CEO), which contains cinnamaldehyde as its major compound, has been reported to possess antioxidant activity to prevent DNA damage. The aim of this study is to evaluate the genotoxic and cytotoxic effect of CEO on doxorubicin-induced Chinese Hamster Ovary (CHO-K1) cells. The cytotoxic effect of CEO was determined by MTT assay with the parameter of IC50 while the genotoxic effect was carried out by micronucleus (MN) assay by using acridine orange fluorescent staining with the parameter of MN/1000 cells reduction number. Based on MTT assay, CEO showed cytotoxic activity with the IC50 value of 30 μg/ml and for MN assay, 3 μg/ml (1/10 IC50) of CEO decreased the percentage of micronucleus per 1000 cells up to 94,55%. Thus, the result can be summarized that CEO does not induce genotoxic and has the potency to prevent DNA damage caused by doxorubicin on CHO-K1 cells.Keywords: genotoxic, cinnamomum essential oil (CEO), micronuclei assay, in vitro
Synergistic Combination of Ciplukan (Physalis angulata) Herbs Ethanolic Extract and Doxorubicin on T47D Breast Cancer Cells Inna Armandari; Kartika Dyah Palupi; Sofa Farida; Adam Hermawan; Ratna Asmah Susidarti; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 1, No 1 (2010)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev1iss1pp26-31

Abstract

Doxorubicin is one of chemotherapeutic agent widely used in breast cancer treatment, but in high dose doxorubicin gives negative side effect, including vomit, nausea, immune suppression, and cardiac toxicity. This toxicity hopefully could be reduced by combination chemotherapy using natural herbs such as ciplukan herb. This research was conducted to explore cytotoxic activity of single ciplukan herbs ethanolic extract and its combination with doxorubicin on T47D breast cancer cells. Cytotoxic activity of ciplukan herbs ethanolic extract only and its combination with doxorubicin were tested on T47D cells using MTT assay to obtain IC50 value and combination index (CI), respectively. Single extract showed cytotoxic activity on T47D cells with IC50 value of was 160 µg/ml. Thus, combination treatment from ciplukan herbs ethanolic extract and doxorubicin showed synergistic effect (CI<1,0). This effect was reached at concentration of ciplukan herbs ethanolic extract-doxorubicin 80 μg/ml- 2 nM, 80 μg/ml-4 nM, and 80 μg/ml-8 nM. This research indicated that ciplukan herbs ethanolic extract is potential to be applied as co-chemotherapeutic agent in breast cancer therapy.Key word : ciplukan herbs, doxorubicin, co-chemotherapy, T47D cells
Ethanolic Extract of Papaya (Carica papaya) Leaf Exhibits Estrogenic Effects In Vivo and In Silico Raisatun Nisa Sugiyanto; Rahmi Khamsita; Marvin Lambertus; Rohmad Yudi Utomo; Ratna Asmah Susidarti
Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev3iss2pp384-390

Abstract

The menopause women have the low level of estrogen in the body. The lack of estrogen changes physiological function in women’s body that affects in health condition. Carica papaya L. leaf contains flavonoid quercetin which exhibits estrogenic effect. The aim of this study is to determine the estrogenic effect of papaya leaves extract (PLE) in vivo, and in silico. Papaya leaves were extracted by ethanol 70% maceration. The in silico study were done by molecular docking between quersetin and Estrogen Receptor (ERα and ERβ) to obtain the docking score. Based on this study, docking score of quercetin was almost similar to the native ligand of ER. The in vivo study was done as follow: 36 female rats Sprague Dawley divided into six groups.  The groups are shame-ovariectomized (S-OVX), control ovariectomized (OVX), CMC-Na control (OVX+CMC-Na), positive control (OVX+Estradiol), and the PLE treatment groups dose 750 mg/kgBW (OVX+750mg/kgBW) and dose 1000 mg/kgBW (OVX+1000 mg/kgBW). Administrations of PLE were done in three weeks orally, while estradiol was administrated intraperitonially. The mammae and uterine were sliced for analysis. Based on the study, the treatment of PLE increased the number of mammae lobules and uterine weight as well as estrogen does.  In summary, PLE can be developed as a source of phytoestrogens.Keywords: Carica papaya L., phytoestrogen, estrogen receptor, mammae lobule, uterine
Naringenin Enhances the Anti-Tumor Effect of Doxorubicin on HeLa Cervical Cancer Cells Through Cytotoxic Activity and Apoptosis Induction Larasati Larasati; Indri Kusharyanti; Adam Hermawan; Ratna Asmah Susidarti; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev2iss3pp325-333

Abstract

Naringenin, an abundant flavanon in the peel of citrus fruits is reported to possess anti-proliferative effect in many cancer cells. Herein, we investigated the cytotoxic effect and apoptosis induction of naringenin in combination with doxorubicin on HeLa cells. The cytotoxicity assay of naringenin, doxorubicin, and their combination were carried out by using MTT assay. Cell viability was used as the parameters to evaluate combination effectiveness. Cell cycle distribution was determined by flow cytometry and analyzed using ModFit LT 3.0 program. Apoptosic assay was done by double staining method using Ethidium Bromide-Acridine Orange. Investigation on the expression of Bax and Bcl-2 were determined by immunocytochemistry method. Naringenin and doxorubicin showed cytotoxic effect on HeLa cells with their IC50 values of 195 µM and 1 µM, respectively. Whereas combination of naringenin - doxorubicin showed greater cytotoxicity compared the single treatment of doxorubicin. The strongest cytotoxic activity was observed at a combination of 100 µM naringenin and 0,5 µM doxorubicin. Single treatment of 0,5 µM doxorubicin for 24 hours on HeLa cells induced S-phase arrest while 100 µM naringenin did not affect on HeLa cell cycle. The combination induced S-phase arrest with the increased of sub-G1 phase percentage. In accordance with the flow cytometry results, the double staining apoptosis assay results showed the increase of apoptotic cells. Naringenin, doxorubicin, and their combination also increased the expression of Bax and decreased the expression of Bcl-2. These results concluded that naringenin was a potential co-chemotherapy agent for cervical cancer due to its synergism with doxorubicin.Keywords: co-chemotherapy, naringenin, doxorubicin, HeLa cells, cytotoxicity, cell cycle, apoptosis
Ethanolic Extract of Moringa oleifera L. Increases Sensitivity of WiDr Colon Cancer Cell Line Towards 5-Fluorouracil Kholid Alfan Nur; Herwandhani Putri; Fany Mutia Cahyani; Aulia Katarina; Ratna Asmah Susidarti; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev1iss2pp124-128

Abstract

For more than four decades, combination chemotherapy (co-chemotherapy) has been employed as a means to increase the effectiveness of chemotherapy regiments. The aim of our research is to investigate the activity of Moringa oleifera L. (tanaman kelor) ethanolic extract (MEE) as a co-chemotherapy agent with 5-fluorouracil (5-FU) on WiDr colon cancer cell line. Evaluation of MEE potency as a co-chemotherapy agent with 5-FU was based on cytotoxic activity based on percent cell viability via MTT assay, and based on apoptosis observation via the double staining method using acrydin orange – ethidium bromide (AE) as the staining reagent.Cytotoxicity evaluation of single treatment using concentrations of 5, 20, 50, 100,125, and 250 µg/ml of MEE reduced cell viability 24 hours post-treatment. 5, 50, and 250 µg/ml of MEE was chosen as the combination concentrations with 1000 µM 5-FU. MTT assay 24 hours and 48 hours post-combination treatment showed significant cell viability reduction in comparison to those of single treatments. Apoptosis observation using the double staining method shows the presence of apoptotic cells 48 hours post combination treatment. MEE is a potential co-chemotherapy agent by increasing the sensitivity of WiDr colon cancer cell line towards 5-FU.Keywords: co-chemotherapy, 5-fluorouracil, Moringa oleifera L., colon cancer
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.
Co-Authors Abdul Karim Zulkarnain Adam Hermawan AGUSTINUS YUSWANTO ANNISA KARAMITA Aulia Katarina BAMBANG SULISTYO ARI SUDARMANTO EDIATI EDIATI Edy Meiyanto EDY MEIYANTO Edy Meiyanto Edy Meiyanto ENDAH PUJI SEPTISETYANI Fany Mutia Cahyani Herwandhani Putri Indri Kusharyanti Inna Armandari Jenie, Riris Istighfari Kartika Dyah Palupi Kholid Alfan Nur Larasati Larasati Layung Sekar Sih Wikanthi Marchaban Marchaban Marvin Lambertus Muthi Ikawati Nindi Wulandari Normaidah, Normaidah Nur Fitra Sari Nurramadhani A. Sida Rahmi Khamsita Rahmi Khamsita Raisatun Nisa Sugiyanto Raisatun Nisa Sugiyanto Riris Istighfari Jenie Rohmad Yudi Utomo SENDY JUNEDI SISMINDARI SISMINDARI Sofa Farida SRI HANDAYANI Sri Handayani Sri Handayani Sri Noegrohati Subagus Wahyuono WARSINAH WARSINAH Yogi Ertanto Yuni Fajar Esti Zalinar Udin