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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 | Full PDF (412.628 KB) | 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.
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 | Full PDF (398.212 KB) | 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 ?g/mL respectively. The combination of sappan wood 15 ?g/mL and bitter ginger 8, 12, 24, and 60 ?g/mL produced synergistic effect with the CI value of 0.57-0.85. Sappan wood 15 ?g/mL combined with bitter ginger 8 and 24 ?g/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.
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

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (4.399 KB)

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

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (318.106 KB)

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.  
The synergistic effect of doxorubicin and ethanolic extracts of Caesalpinia sappan L. wood and Ficus septica Burm. f. leaves on viability, cell cycle progression, and apoptosis induction of MCF­7 cells Haryanti, Sari; Pramono, Suwijiyo; Murwanti, Retno; Meiyanto, Edy
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 (1290.778 KB) | DOI: 10.22146/ijbiotech.26105

Abstract

Caesalpinia sappan L. and Ficus septica Burm. f  known asa potential plant with wide variety of medicinal properties, including anticancer. Present study was aimed to explore cytotoxic effect ofsappan wood (ECS) and awar-awar leaves (EFS), and its combination with doxorubicin (dox) on MCF-7 cells focusing on cell cycle progression and apoptosis induction.The result of MTT assay showed that single treatment of ECS and dox performed cytotoxic effect with the IC50 value of 32 µg/mL and 6 µM respectively, while EFS performed low cytotoxic effect with the IC50 value of 282 µg/mL. The combination of ECS with EFS and doxorubicin showed synergistic cytotoxic effect. Flow cytometry analysis revealed that combination of ECS (16 µg/mL) with EFS (8 µg/mL) and doxorubicin (2 µM) induced apoptosis, and cell accumulation at sub-G1 and G2/M phases.Immunoblotting assay confirmed the apoptosis induction of this combination through increasing of cleavage of PARP-1. Based on these results, the synergistic cytotoxic effect of this combinationwas through G2/M phase accumulation and apoptosis inductionand potentially to be developed as co-chemotherapeutic agent.
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

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (318.106 KB) | DOI: 10.22146/ijbiotech.7809

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.  
The aqueous extract of Gerrardanthus macrorhizus caudex enhanced doxorubicin activity in MCF-7 human breast cancer cells Haryanti, Sari; Widiyastuti, Yuli; Wahyono, Slamet
Indonesian Journal of Biotechnology Vol 23, No 1 (2018)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (2003.76 KB) | DOI: 10.22146/ijbiotech.32519

Abstract

Gerrardanthus macrorhizus (GM) caudex, is traditionally used in cancer therapy by the Tetun people in Belu District, East Nusa Tenggara Province, Indonesia, where it is known as “akar batu”. This study aimed to explore the cytotoxic effects of G. macrorhizus caudex aqueous extract, as well as its combination with doxorubicin, on MCF-7 cells. Also investigated were the possible mechanisms of interaction through cell cycle progression and apoptosis induction. Single treatments of 5–320 µg/mL of the extract showed morphological alterations in MCF-7 cells, but did not show any cytotoxic effect. Combining the extract with doxorubicin resulted in a synergistic cytotoxic effect. Doxorubicin concentrations equivalent to 1/12, 1/8, and 1/5 fold of the IC50 combined with 20 µg/mL decreased viability to 48%. We then explored the combination effect of doxorubicin 0.4 µM with GM 5 and 20 µg/mL using a flow cytometer. A low concentration of the extract (5 µg/mL) combined with 0.4 µM of doxorubicin resulted in slight cell cycle modulation by G1, G2M arrested and apoptosis induction. The combination of doxorubicin and a higher concentration of the extract (20 µg/mL) did not show cell cycle modulation, and led to necrosis. Therefore, G. macrorhizus caudex at low concentrations has the potential to be developed further as a co-chemotherapeutic agent.
Evaluation of The Genotoxicity of Three Food Additives using CHO-K1 Cells under in vitro Micronucleus Flow Cytometry Assay Lestari, Beni; Novitasari, Dhania; Putri, Herwandhani; Haryanti, Sari; Sasmito, Ediati; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 8, No 2 (2017)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev8iss2pp74-80

Abstract

Exposure of genotoxic substances come from various sources such as food additives. The aim of this study is to evaluate the genotoxicity of food additives in CHO-K1 cells by micronucleus test flow cytometry. The food additives: sodium saccharine (SS), monosodium glutamate (MSG), and sodium benzoate (SB) were assessed by in vitro cytotoxicity and genotoxicity using Chinese Hamster Ovary-K1 (CHO-K1) cells. The cytotoxic effect of those compounds was evaluated by MTT Assay on CHO-K1 Cells. The genotoxic evaluation was observed by in vitro micronucleus test by flowcytometry with double staining method. The results showed that the three compounds did not perform cytotoxic effect, increased the frequency of micronucleus, and changed the cell cycle profiles. In general, these studies obtained that none of three food additives showed cytotoxic and genotoxic effect on CHO-K1 cells. Micronucleus test using flow cytometry is suitable for this purpose study.Key words : food additives, genotoxic, cytotoxic, micronucleus
Different 4T1 Cells Migration under Caesalpinia sappan L. and Ficus septica Burm.f Ethanolic Extracts Haryanti, Sari; Murwanti, Retno; Putri, Herwandhani; Ilmawati, Gagas Pradani Nur; Pramono, Suwijiyo; Meiyanto, Edy
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/indonesianjcanchemoprev8iss1pp21-26

Abstract

Secang (C. sappan L.) and awar (F. septica Burm.f) are known of Indonesian traditional medicine that highly consumed throughout centuries in order to cure various diseases. Recently, researchers also concern about its effects as anti-cancer on various cell types. This study was conducted to understand the ethanolic extract of C. sappan L. (ECS) and F. septica Burm.f (EFS) effects on 4T1 cells migration at various concentrations. Firstly, we examine cell proliferation profile with MTT assay under treatment with the extracts and obtained the IC50 value of ECS (20 μg/mL) and EFS (15 μg/mL). Subsequent assay conducted was to examine the cells migration under low concentration resulting in the migration inhibitory effect of both EFS and ECS with different intensity.  EFS performed better migration inhibitory effect than ECS. Finally, we conducted gelatin zymography and western blot and revealed that the migration inhibitory effect of EFS may correlate to the lowering of protein expression of MMP9 and Rac-1 after 24 hours of treatment. We conclude that both extracts are potential to be developed as anticancer agent and EFS is more potent for anti-metastasis.Keywords: C. sappan L., F. septica Burm.f, 4T1, anti-migration
Ursolic Acid Enhances Doxorubicin Cytotoxicity on MCF-7 Cells Mediated by G2/M Arrest Arifin, Ibrahim; Hermawan, Adam; Ikawati, Muthi'; Haryanti, Sari; Anindyajati, Anindyajati; Meiyanto, Edy
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/indonesianjcanchemoprev3iss3pp410-418

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