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Edy Meiyanto
Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada
Biochemistry, Genetics & Molecular Biology Medicine & Pharmacology

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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
Combination of Leunca Herb Ethanolic Extract and Doxorubicin Suppresses HeLa Cells’ Growth Sarmoko Sarmoko; Dyaningtyas Dewi Pamungkas Putri; Endah Puspitasari; Anindyajati Anindyajati; 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/indonesianjcanchemoprev2iss3pp281-285

Abstract

Leunca (Solanum nigrum L.)ethanolic extractshowedcytotoxic activity on several cancer cell lines (HepG2, HT-29) and showed anti-proliferative activityon MCF-7 cells. Its application as a combinationagent in chemotherapy will increase the effectivity and reduce the toxicity of chemotherapy. We predict that application of combinatorial chemotherapy in cancer treatment will be more effective and less toxic compared to single treatment. Our research aims to investigate the cytotoxic activitiy of leunca herbs ethanolic extract alone and in combination with doxorubicin on HeLa cell line. MTT assay was conducted to measure the growth inhibitory effect of leunca herbs ethanolic extract and combinatorial treatments. Leunca herb ethanolic extract (5, 50, 250 μg/ml) increased the cytotoxic effect of  doxorubicin compared to doxorubicin alone. The strongest cytotoxic activity resulted from the combination of 250 μg/ml leunca herbs ethanolic extract and 250 nM doxorubicin. Based on our results, leunca herbs ethanolic extract is a potential chemopreventive agent, while its molecular mechanism needs to be explored.Keywords : Leunca herbs ethanolic extract, doxorubicin, HeLa, MTT assay
Banana Peels (Musa paradisiaca L.) Extract as Phytoestrogen on Ovariectomized Mice Mammary Gland Development by Inducing c-Myc Expression Nanda Resa Pratama; Yurista Gilang; Rita Riata; Adam Hermawan; Muthi' Ikawati; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 2, No 1 (2011)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev2iss1pp151-158

Abstract

Hormone Replacement Therapy (HRT) is therapy for estrogen deficiency and post menopausal syndromes, but high cost and unwell-secured therapy. One of alternative therapy is the usage of phytoestrogens. The banana peel contains flavones, flavonol, flavanone and polimethoxyflavone which are potential as phytoestrogen. The purpose of this study was to examine the estrogenic effect of banana peel extract (BPE) development of mammary gland of ovariectomized rats. Estrogenic effects was examined based on in vivo and in silico experiment. For in vivo experiment, female Sprague-dawley rats aged 50 days were ovariectomized. At 70 days of age, 12 rats were treated with BPE 500 mg/kgBB and 1000mg/kgBB, 5 rats were treated with estradiol 2μg/day while others served as control were treated with CMC-Na 0.5% and sacrificed 2 weeks later. The base line ovariectomized rats and base line non-ovariectomized rats were sacrificed at 70 days of age. The in silico experiment examined by molecular docking between myricetin and estrogen receptor alpha (ER-α). The result of in vivo experiment showed that 1000 mg/kgBW BPE induced c-Myc expression and enhance ovariectomized rat mammary gland development significantly. Meanwhile, molecular docking showed that there are hydrogen bond interaction between bioactive compound in BPE and Estrogen Receptor (ER)-α but less powerfull than estrogen and ER-α interaction. In summary, BPE can act as an estrogen agonist, resulting in the enhancement of c-Myc expression.Keywords: banana peels extract (BPE), phytoestrogen, mammary gland, ovariectomized rats
Synergistic Effect of Arecoline in Combination with Doxorubicin on HeLa Cervical Cancer Cells Astrid Ayu Maruti; Fikri Amalia; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 6, No 2 (2015)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev6iss2pp64-70

Abstract

Arecoline, the main alcaloid of Areca cathecu L has been proven to posses cytotoxic activity against various cancer cell lines. The research conducted to examine the cytotoxic activity of arecoline alone and its combination with doxorubicin against HeLa cervical cancer cell line. Single treatment of arecoline in various concentration on HeLa cancer cell were done followed by the combinational treatment with doxorubicin. The cell viability as the parameter of cytotoxicity was measured using MTT (3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide) assay. The apoptotic effect was examined by double staining assay using etidium bromide–acridin orange.  Arecoline did not show potent cytotoxicity effect against HeLa since the value of IC50 is 462 µM. The combinational treatment of arecoline and doxorubicin showed synergicity with the optimum CI value is 0,48 given by the treatment of 30mM arecoline combined with 125 nM doxorubicin. The result of this study shows that arecoline has potential to be proposed as co-chemotherapeutic agent for cervical cancer. However, further study on its molecular mechanism needs to be conducted. Keywords:  cinnamon essential oil, doxorubicin, T47D cells, combination cytotoxicity
Ficus septica Burm. F. Leaves Ethanolic Extract Induces Apoptosis in 7,12-Dimethylbenz[A]Nthracene-Induced Rat Liver Cancer Quatitavely Dita Brenna Septhea; Anindyajati Anindyajati; Andita Pra Darma; Ika Nurzijah; Agung Endro Nugroho; 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/indonesianjcanchemoprev2iss2pp255-260

Abstract

The chemopreventive effect of Ficus septica Burm. f. leaves ethanolic extract (FLEE) was studied in 7,12-dimethylbenz[a]nthracene(DMBA)-induced rat liver cancer. Rats were divided into 5 group, 5 rats (5 wk of age Sprague Dawley rat) in each group. Group 1 was control diet group, administered with 0,5% CMC-Na as vehicle. FLEE was administered 750 mg/kgBW and 1500 mg/kgBW starting 4 wk until 5 wk after DMBA administration at the first until fifth wk to group 2 and group 3. Group 4 was control extract group, administered  with 750 mg/kgBW and group 5 was DMBA group. DMBA is a carcinogen to induce liver cancer was also administered in DMBA control group and all animals were necropsied at 6 wk after DMBA administration. Activity of inducing apoptosis was detected using Double Staining method in 750 mg/kgBW FLEE group compared to control group but no in 1500 mg/kgBW FLEE group resulted in 100% dead. Apoptotic cells would have orange flourescence but normal cells would have green flourescence detected by flourescence microscope. To investigate the protein that involved in apoptotic mechanism, we studied p53 expression using Imunohistochemistry (IHC). There was no difference expression of p53 in both tested and control groups. Based on the results, FLEE has a potency as chemoprentive agent because its activity on inducing apoptosis in liver cancer with p53-independent pathway. The mechanism of apoptosis induction of this extract needs to be explored by observing the expression of related proteins.Keywords: apoptosis, Ficus septica, liver cancer, p53 independent pathway
Revealing the Potency of Cinnamon as an Anti-cancer and Chemopreventive Agent Yonika Arum Larasati; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 9, No 1 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev9iss1pp47-62

Abstract

Cinnamon (Cinnamomum spp.), an ancient spice, has been explored as a potential for medicinal purposes. Despite numerous studies about its potency in overcoming of numerous diseases, the potency as anti-cancer would be a challenge. This current article provides a review of the anti-cancer and chemoprevention potency of cinnamon and its major constituents: cinnamaldehyde, cinnamic acid, 2-hydroxycinnamaldehyde, 2-methoxycinnamaldehyde, and eugenol. Comprehensively, cinnamon and its constituents exhibit the anti-cancer and cancer prevention activities through various mechanisms: (1) anti-proliferation, (2) induction of cell death, (3) anti-angiogenesis, (4) anti-metastasis, (5) suppression of tumor-promoted inflammation, (6) immunomodulation, and (7) modulation of redox homeostasis; both in vitro and in vivo. Moreover, cinnamon also shows the synergistic anti-cancer effect with well-known anti-cancer drugs, such as doxorubicin, which support its potency to be used as a combination chemotherapeutic (co-chemotherapeutic) agent. However, further study should be established to determine the exact target molecule(s) of cinnamon in the cancer cells.Keywords: cinnamon, spice, cancer, anti-cancer, chemopreventive
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
Taraxacum officinale Leaves Ethanolic Extract as Immunostimulatory Agent For Reducing Side Effect of Doxorubicin in Sprague Dawley Rats Sri Kasianningsih; Erlina Rivanti; Ratih Hardika Pratama; Nanda Resa Pratama; Muthi' Ikawati; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 2, No 1 (2011)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev2iss1pp135-140

Abstract

Doxorubicin as chemotherapeutic agent causes immunosuppresive. The aim for this study to determine the effect of ethanolic extract of Taraxacum oficinale (ETO) in immunity system of Sprague Dawley rat that induced by doxorubicin to observe the profile of immunity cells. Sprague Dawley rats were divided into five groups each groups contain five rats: control doxorubicin group, doxorubicin dose 4,67 mg/kgBW+ ETO dose 1000 mg/kgBW, doxorubicin dose 4,67 mg/kgBW+ ETO dose 500 mg/kgBW, control extract group, and without treatment. Then the number of leukocytes, lymphocytes and neutrophils were analyzed by hematology analyzer, whereas CD8+ T lymphocytes by flowcytometry. Results showed groups of doxorubicin combined with ETO dose 1000 mg/kgBW and 500 mg/kgBW increased the number of leukocytes, lymphocytes, neutrophils,  cytotoxic CD8 + T cells T cells compared to control doxorubicin group. These data presents that etanolic extract of Jombang leaves has immunostimulatory activity and potential as co-chemotherapy agents. Molecullar mechanism underlaying it’s immune activity need to be explored in detail.Keywords: co-chemotheraphy, doxorubicin, immunostimulatory, in vivo Taraxacum officinale
Antiproliferative Activity of Ethanolic Extract of Ciplukan Herbs (Physalis angulata L.) on 7,12-Dimethylbenz[A]Nthracene-Induced Rat Mammary Carcinogenesis Ameilinda Monikawati; Sofa Farida; Laras Widawaty Putri; Yurista Gilang Ikhtiarsyah; 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/indonesianjcanchemoprev2iss2pp228-233

Abstract

Physalis angulata L. is an annual herb widely used as popular medicine for the treatment of cancer. Physalis angulata L. ethanolic extract (PEE) has been demonstrated to have strong cytotoxic activity against breast cancer, inhibited cancer cell’s proliferation and induced cell cycle arrest. The aim of our study is to investigate the effect of PEE as a cancer chemopreventive agent on 7,12-dimethylbenz[a]nthracene (DMBA)-induced rats mammary. The antiproliferative activity was characterized by monitoring the histopatology representation and expression of cell proliferation on DMBA-induced mammary rats that were treated with PEE against control groups. The histopatology representation were analyzed by Haematoksilin Eosin (HE) staining method, while proliferative activity was detected by AgNOR method. The HE staining results showed significant differences in cells morphology of treatment groups compared to the control groups. Thus results suggest that PEE was able to repair morphology of cells undergoing carcinogenesis. AgNOR method showed decreasing occurrence of black dots between treatment and control groups. Thus, we conclude that PEE has an antiproliferative activity on DMBA-induced rat mammary. Therefore, the ethanolic extract of Physalis angulata herbs is a potential chemopreventive agent on cancer. Further study on its molecular mechanism needs to be explored.Keywords: Physalis angulata, breast cancer, 7,12-dimethylbenz[a]nthracene, carcinogenesis, antiproliferative
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
Co-Authors Adam Hermawan Agung Endro Nugroho Ameilinda Monikawati Andita Pra Darma Anindyajati Anindyajati Annisa Novarina Astrid Ayu Maruti Aulia Katarina Dita Brenna Septhea Dyaningtyas Dewi Putri Pamungkas Endah Puspitasari Erlina Rivanti Erna Prawita Setyowati Etyk Yunita Anjarsari Fany Mutia Cahyani Fikri Amalia Fortunella Tjondro Herwandhani Putri Ika Nurzijah Indri Kusharyanti Inna Armandari Jenie, Riris Istighfari Kartika Dyah Palupi Kholid Alfan Nur Laras Widawaty Putri Larasati Larasati Maya Fitria Muthi Ikawati Nanda Resa Pratama Nita Kristina Nunuk Aries Nurulita Prisnu Tirtanirmala Raditya Prima Istiaji Raisatun Nisa Sugiyanto Ratih Hardika Pratama Ratna Asmah Susidarti Rita Riata Rohmad Yudi Utomo Sarmoko Sarmoko Sofa Farida Sri Handayani Sri Kasianningsih Sugiyanto Sugiyanto Yonika Arum Larasati Yurista Gilang Yurista Gilang Ikhtiarsyah Zalinar Udin