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Ursolic Acid Enhances Doxorubicin Cytotoxicity on MCF-7 Cells Mediated by G2/M Arrest Arifin, Ibrahim; Hermawan, Adam; Ikawati, Muthi; Haryanti, Sari; Anindyajati, .; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 3, No 3 (2012)
Publisher : Indonesian Research Gateway

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Abstract

Ursolic acid has been widely known to possess biological activity against numerous tumor cell lines. Previous studies revealed its cytotoxicity on several cancer cells  in vitro by either inducing apoptosis or cell cycle modulation. This  study was conducted to investigate ursolic  acid’s  cytotoxicity  solely  and  in  combination  with  a  chemotherapeutic  agent, doxorubicin,  on  MCF-7  breast  cancer  cells,  followed  by  observation  on  its  mechanism. Cytotoxicity of single and combinational treatment of ursolic acid and doxorubicin on MCF-7 breast cancer cells were conducted by using MTT assay. Single treatment was then evaluated by  determining  IC50  value,  while  combinational  treatment  was  evaluated  by  analyzing  cell viability  and  evaluating  combination  index  (CI).  To  explore  the  mechanism  underlying cytotoxic  effect  on  respected  cells,  further  analysis  on  cell  cycle  profile  of  single  and combinational treatment was conducted by flow cytometry. Twenty four hours treatment of ursolic  acid  inhibited  MCF-7 cells’ growth with  IC50  value  of  37  µM,  while  combinational treatment  showed  that  several  concentration  combinations  of  ursolic  acid  and  doxorubicin exhibited  synergism  of  cytotoxic  activity  on  MCF-7  cells,  giving  optimum  CI  value  of  0.54. Flow cytometric analysis showed that combinational treatment induced G2/M arrest in MCF-7  cells.  These  results  show  that  ursolic  acid  is  promising  to  be  developed  as  either  single chemopreventive  agent,  or  as doxorubicin’s co-chemotherapeutic  agent  in  breast  cancer treatment.  Observation  on  the  selectivity  as  part  of  safety  aspect  together  with  in silico,  in vitro, and in vivo study on its molecular mechanism should be conducted.Keywords: ursolic acid, doxorubicin,co-chemotherapeutic agent, breast cancer, cell cycle
Ethanolic Extract of Hedyotis corymbosa L. Increases Cytotoxic Activity of Doxorubicin on MCF-7 Breast Cancer Cell Haryanti, Sari; Junedi, Sendy; Meiyanto, Edy
Indonesian Journal of Biotechnology Vol 14, No 1 (2009)
Publisher : Universitas Gadjah Mada

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Abstract

Hedyotis corymbosa L. with ursolic acid as the main compound is one of the plants that has been used for traditional medicine including to cure breast cancer disease. The aim of this research is to examine the cytotoxic activity of rumput mutiara herb ethanolic extract (ERM) and its effect in combination with doxorubicin against MCF-7 breast cancer cell line as cell model of doxorubicin resistance. Hedyotis corymbosa L. herb powder extraction was done by maceration using ethanol 96% then the extract is detected for ursolic acid content. Cell viability assay of ERM, doxorubicin and  the combination of ERM and doxorubicin treatments were carried out by MTT assay to determine IC50 and CI (Combination Index). Cell cycle distribution was determined by flowcytometry. Apoptosis assay was performed by ethidum bromide-acridine orange DNA staining method. Investigation on Bcl-2 expression was determined by immunocytochemistry method. Thin Layer Chromatography of ERM had similar Rf with ursolic acid standard: 0,6. ERM and doxorubicin inhibited cell growth against MCF-7 with IC50  of 77 µg/mL and 349 nM (0,19 µg/mL) respectively. Combination of ERM and doxorubicin showed synergistic effect (CI 0.66-0.99). Combination of 25 ìg/mL ERM- 200 nM doxorubicin induced apoptosis and decreased Bcl-2 expression but showed no cell accumulation on cell cycle. Doxorubicin induced high cell accumulation in G2/M phase, but ERM at the concentration of 25 ìg/mL had a low effect in G1 phase, and ERM IC50 did not induce cell accumulation otherwise apoptosis. These results concluded that the apoptosis mechanism of combination doxorubicin-ERM is mediated by cell cycle arrest and non cell cycle arrest. Therefore ERM has a potential activity to be developed as co-chemotherapeutic agent.  
Phytochemical and Cytotoxic Evaluation of Krangean Fruits Extracts Against HeLa, MCF-7, and HepG2 Cancer Cell Line Widiyastuti, Yuli; Marfuatush Sholikhah, Ika Yanti; Haryanti, Sari
Biosaintifika: Journal of Biology & Biology Education Vol 11, No 3 (2019): Article-in-Press
Publisher : Department of Biology, Faculty of Mathematics and Sciences, Semarang State University . Ro

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15294/biosaintifika.v11i3.18073

Abstract

Krangean [Litsea cubeba (Lour.) Pers.] is one of ancient aromatic plants in Indonesia which is used as traditional medicines such as for carminative, stimulant, stomach ache and expectorant. Otherwise, the anticancer activity of this plant has not been explored extensively. This research aimed to investigate phytochemical content and cytotoxic activity of krangean fruits extract on human cancer cell line in vitro. The research was an in vitro experimental design and the cytotoxic activity was carried out with MMT assay.  The phytochemical compounds were characterized by TLC (Thin Layer Chromatography). MTT assay was done to observe morphology and viability of HeLa cervical cancer, MCF-7 breast cancer, and HepG2 liver cancer cell line. The results showed that TLC characterization of chloroform and methanolic extracts of Litsea cubeba revealed similar profile, with the major compound found were terpenoid and alkaloid. The MTT assay found that both extracts had strong inhibition on HeLa cell line. Chloroform extract exhibited stronger cytotoxic activities compared to methanol, with the IC50 values of 37.3 and 64.7 ?g/mL respectively. While, the both extract have moderate cytotoxic activities to HepG2 and MCF-7 cancer cell line indicated by IC50value more than 100 mg/mL. The benefit of this study is to provide the scientific information regarding the potency of krangean fruit as herbal natural medicine for cervical cancer therapy.
Medicinal Plants used for Antihypercholesterolemia in Ethnic Groups of Celebes Island, Indonesia: Pemanfaatan Tumbuhan Obat sebagai Antihiperkolesterolemia di Berbagai Etnis di Pulau Sulawesi, Indonesia Rahmawati, Nuning; Haryanti, Sari; Yanti Marfuatush Sholikhah, Ika; Subositi, Dyah; Widodo, Harto; Mujahid, Rohmat; Widiyastuti, Yuli
Jurnal Tumbuhan Obat Indonesia Vol. 16 No. 2 (2023): December 2023
Publisher : Universitas Tidar

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.31002/jtoi.v16i2.1025

Abstract

This study aimed to identify the utilization of medicinal plants used by selected traditional healers who met inclusion criteria to treat high cholesterol levels in ethnic groups of Celebes Island, Indonesia. Data collection was carried out through interviews, observation, and sample collection. This study revealed 67 concoction information and identified the use of 48 plant species distributed in 32 families among 39 healers in 20 ethnic groups in Celebes Island. Peperomia pellucida (L.) Kunth (UV=0.21), lamiaceae (15.63%), and leaves (57.35%) were determined as the most prominent species, family, and plant part used. The most widely prescribed rule of use is internal administration (94.03%) with a frequency of 3x1 per day (44.78%) for a week to a month (56.72%). However, conservation efforts need to be initiated immediately since more than 50% of healers made no cultivation efforts
Efek Sinergis Kombinasi Ekstrak Etanolik Kayu Secang dan Rimpang Lempuyang pada Sel Kanker Payudara MCF-7 Haryanti, Sari; Sholikhah, Ika Yanti M.; Widiyastuti, Yuli
Jurnal Kefarmasian Indonesia VOLUME 9, NOMOR 1, FEBRUARI 2019
Publisher : Pusat Penelitian dan Pengembangan Biomedis dan Teknologi Dasar Kesehatan

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22435/jki.v9i1.324

Abstract

Cancer is one of critical, chronic, and complex disease, also becoming the high cause of death in the world. Brazilin and brazilein in sappan wood (Caesalpinia sappan L.) and zerumbone in bitter ginger rhizome (Zingiber zerumbet L.) are known having cytotoxic activity with different mechanisms. This study aimed to examine combination effect of sappan wood and bitter ginger rhizome. Sappan wood and bitter ginger rhizomes macerated with ethanol 96% for 3x24 hours, filtered, and evaporated to obtain dried extract.Cytotoxic effect on MCF-7 cells was done using MTT assay. Combination Index (CI) was determined by CompuSyn based on the result of cytotoxic combination. Cell cycle profile and apoptosis induction was analyzed by flow cytometry. Sappan wood extracts and bitter ginger rhizome exhibited cytotoxic effects on MCF-7 cells with the IC50 values of 30 and 155 μg/mL respectively. The combination of sappan wood 15 μg/mL and bitter ginger 8, 12, 24, and 60 μg/mL produced synergistic effect with the CI value of 0.57-0.85. Sappan wood 15 μg/mL combined with bitter ginger 8 and 24 μg/mL showed cell cycle inhibition at G2/M phase. The combination also increased apoptosis induction compared to untreated cells and its single treatment.The combination of sappan wood ethanolic extracts and bitter ginger rhizome showed synergistic cytotoxic effect. Its synergism effect revealed through cell cycle arrested at G2/M phase and acceleration of apoptotic induction.
Efek Sitotoksik Formula Jamu Daun Sirsak, Buah Takokak, dan Umbi Bidara Upas terhadap Sel Kanker Payudara MCF-7 Widiyastuti, Yuli; Marfuatush Sholikhah, Ika Yanti; Haryanti, Sari
Jurnal Kefarmasian Indonesia VOLUME 9, NOMOR 2, AGUSTUS 2019
Publisher : Pusat Penelitian dan Pengembangan Biomedis dan Teknologi Dasar Kesehatan

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22435/jki.v9i2.1049

Abstract

Cancer is one of the leading cause of death in the world. Complicated and high cost treatments of cancer encourages people to look for alternative treatments among others using medicinal plants. Some medicinal plants that are empirically claimed to have anticancer effect are soursop (Annona muricata), takokak (Solanum torvum), and bidara upas (Merremia mammosa). However, these medicinal herbs have not been tested for cytotoxic activity against MCF-7 cancer cells. The purpose of this study was to determine the cytotoxic activity of the anticancer herbal formula consisting those three plants. The effect of each single extract and the combination formula were tested for their activity on cell viability of MCF-7 with MTT assay method. The herbal formula with the most active combination of medicinal plant extracts was further tested for its activity on the expression of Bcl-2 protein by immunocytochemistry methods. The results showed that each single extract and the combination formula gave cytotoxic effect on MCF-7 breast cancer cells. Formula A, consisted of a mixture of soursop leaves, takokak fruit, and bidas upas bulb with a ratio of 1:1:1, results in highest inhibition of the viability of MCF-7 cells with IC50 values of 48 µg/ml. The formula also enhances the apoptosis process in MCF-7 cells which is shown by decreasing the expression of antiapoptotic Bcl-2 proteins.
ANTIMALARIAL MEDICINAL PLANTS USED BY TRADITIONAL HEALERS IN BENGKULU PROVINCE OF INDONESIA Susanti, Dian; Putra, Aditya Dwi Permana; Safrina, Devi; Wijaya, Nur Rahmawati; Adi, M Bakti Samsu; Mujahid, Rohmat; Rukmana, Rizal Maarif; Subositi, Dyah; Haryanti, Sari; Siswanto, Usman; Widiyastuti, Yuli
BIOTROPIA Vol. 31 No. 3 (2024): BIOTROPIA Vol. 31 No. 3 December 2024
Publisher : SEAMEO BIOTROP

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.11598/btb.2024.31.3.2318

Abstract

Article Highlights- This research provides information on the use of medicinal plants for treating malaria among ethnic groups in Bengkulu Province.- This research was part of RISTOJA (Research on Medicinal Plants), national research conducted by the Ministry of Health of the Republic of Indonesia.- Several compounds found in medicinal plants used by traditional healers in the Bengkulu Province have been scientifically proven to be effective as antimalarial medication.AbstractMalaria is a disease with a high mortality rate and is still a significant problem in Indonesia and globally. One of the provinces in Indonesia that uses a diversity of medicinal plants to treat malaria is Bengkulu Province. This research aims to inventory and evaluate the use of medicinal plants as malaria drugs in Bengkulu Province. The research methods used were observation, interviews, and the collection of samples. Respondents were traditional healers from seven ethnic groups in Bengkulu. Plant species, use value (UV) parameters, fidelity level (FL), family use value (FUV), relative frequency of citation (RFC), and plant parts value (PPV) were analyzed. This study found 32 specific herbal concoctions and identified the use of 47 plant species in 28 families used by 20 healers in 6 ethnic groups of Bengkulu. The species Carica papaya, Peronema canescens, and Tinospora crispa have the highest use value, fidelity level, and relative frequency of citation. The Lamiaceae and Caricaceae families have the highest family use value (0.15). The leaves (43.9%) and barks (13.6%) were the most frequently utilized parts of medicinal plants to overcome malaria. Decoction was the method most widely used by traditional healers in Bengkulu to prepare conventional medicine formula.
Stevia Local Tawangmangu Generation M1 Result of Oryzalin Treatment Susanti, Dian; Parjanto, Parjanto; Haryanti, Sari
Jurnal Biodjati Vol 9 No 1 (2024): May
Publisher : UIN Sunan Gunung Djati Bandung

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15575/biodjati.v9i1.31634

Abstract

 Stevia rebaudiana Bert. (Stevia) is used in the commercial and health industries because of its steviol glycosides (stevioside, re­baudioside A, rebaudioside C) and flavonoids. Polyploidy induction of stevia plants using oryzalin was held to increase the diversity and produce superior varieties. This research aims to obtain stevia diver­sity with different characteristics from its diploid. The Tawangman­gu variety of stevia seedlings was experimentally designed using a completely random design. Nine combinations of oryzalin concentra­tions (1.5, 2.5, and 3.5μM) and immersion times (4, 6, and 8 hours) treatments were applied to 15 stevia seedlings each. Stevia without treatment was used as a control. Treatments were applied directly to the shoots on the second internode from the tip. Observations on tar­get shoots included the number of survivors, morphological variables (height, number of internodes, internode length, leaf size, leaf thick­ness, stem diameter, and leaf color), stomata, and plant ploidy level. Data analysis on the number of live plants used frequency and de­scriptively. Morphological data consisting of plant height, number of shoots, number of internodes, internode length, leaf length, leaf width, leaf thickness, and stem diameter were analyzed using boxplot graphs and descriptive to describe the diversity of M1 stevia treatment re­sults. Leaf color and stomata were analyzed descriptively. The results showed that up to 3.5μM concentrations of oryzalin and 6 hours of immersion time were safe to use as a mutation agent with above 67% survival rate. Various oryzalin treatments of Tawangmangu stevia va­rieties yielded polyploidy morphological growth indications in height, number of internodes, internode length, stem diameter, leaf size, leaf thickness, leaf color, stomata, and stem diameter. In addition, there are growth variations such as chimeras, rosettes, and leaf splitting. However, further flow cytometry tests showed that oryzalin concen­tration and immersion duration directly on the vegetative material did not produce polyploid stevia individuals.
Selectivity Index of Alpinia galanga Extract and 1’-Acetoxychavicol Acetate on Cancer Cell Lines Da'i, Muhammad; Meilinasary, Khairunnisa Azani; Suhendi, Andi; Haryanti, Sari
Indonesian Journal of Cancer Chemoprevention Vol 10, No 2 (2019)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev10iss2pp95-100

Abstract

Previous research stated that galangal (Alpinia galanga) extract has a potential as cytotoxic agent with active compound of 1’-Acetoxychavicol Acetate (ACA). The objective of this study was to determine the selectivity of ethanol extract, ethyl acetate fraction, and methanol fraction of of galangal, and ACA on cancer cell lines. Cytotoxic activity was carried out using the MTT method on T47D breast cancer, WiDr colon cancer, HeLa cervical cancer, and Vero normal cell lines. The results showed that galangal ethanol extract and its fractions had selectivity index equal to or less than 2 on cancer cells. Meanwhile, ACA had selectivity index more than 3 on T47D cell and HeLa cell. ACA showed a strong cytotoxic activity against cancer cells T47D, HeLa, and WiDr with IC50 values of 3.14, 7.26, and 12.49 μg/ml, respectively. Based on data, it could be concluded that ACA was the most selective to inhibit T47D cell with a selectivity index of 6.6.Keywords: 1’-Acetoxychavicol acetate, galangal (Alpinia galanga), selective index, cytotoxic
Revealing Chemopreventive Potential of Active Constituents from Medicinal Herbs Used in Indonesia for (Metastatic) Breast Cancer with Particular Molecular Targets Indrasetiawan, Puguh; Haryanti, Sari; Meiyanto, Edy
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/indonesianjcanchemoprev11iss3pp168-186

Abstract

Breast cancer remains as one of the highest causes of cancer-related deaths in the world, including Indonesia. In spite of following the standard protocol therapy, some patients in developing countries consume medicinal herbs as an alternative, complementary, as well as supportive therapies. Several herbs have been recognized to be used for this purpose. Annona muricata, Curcuma longa, Curcuma zanthorrhiza, Curcuma zedoaria, Phyllanthus urinaria, Gynura procumbens, Garcinia mangostana, Morinda citrifolia, and Nigella sativa are some of the plants used as chemopreventive agents with several formulas. Various types of extracts of Annona muricata show anticancer activities in vitro and in vivo. Curcumin, obtained from Curcuma longa and Curcuma zanthorrhiza, acts as p53 regulator and pro-oxidant in MCF-7 cells and also acts as a fatty acid synthase inhibitor in MDA-MB-231 cells. Xanthorrhizol from Curcuma zanthorrhiza has pro-apoptotic activity via modulation of Bcl-2, p53, and PARP-1 protein levels. Curcuma zedoaria contains curcumenone, curcumenol and curdion, which show pro-apoptotic activity in various cell lines and a cancer-induced mouse model. Corilagin and geraniin from Phyllanthus urinaria have different pro-apoptotic effects, in which, the corilagin-caused apoptotic effect is mediated by extrinsic and mitochondrial pathways, whereas geraniin induces apoptosis via ROS-mediated stimulation, both in MCF-7 cells. Thymoquinone from Nigella sativa has been extensively studied for its anticancer activities in recent years. Plants are cultivated, collected and mixed depending on the use as herbal medicines. Active compounds might be formulated if deemed possible. The development of more potential derivatives is also necessary to produce more optimum anti-cancer agents. In conclusion, Indonesian plants and their active constituents show potential activities to be developed as chemopreventive agents.Keywords: Indonesian medicinal herbs, breast cancer, active constituents, molecular targets