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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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Translational Research in Cancer Drug Development Edy Meiyanto; Adam Hermawan; Anindyajati Anindyajati
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/indonesianjcanchemoprev2iss2pp198-211

Abstract

The development of cancer treatment were initiated by the existence of human’s effort to treat by applying certain materials which is mostly part(s) or extracts of plants, which are now adapted as traditional herbal medicine. The discovery of new drugs was based on intuition and empirical evidence. Thus, high luck factor was involved in a successful treatment with unguaranteed reproducibility. One example of drug being developed through conventional drug development is Taxol. Taxol is an extremely complex natural product and requires a bunch of hard work with high level of serendipity to be discovered as antitumor agent. Recently, rapid development in human biology and technology allow a change in drug discovery strategy by minimizing the luck factor. Targeted therapy has been a very promising strategy of drug development research, especially in cancer treatment. Although cancer has been known as a disease with very complex cellular and histo-pathophysiology, the abundance of studies on proteins, such as receptors and hormones, as the hallmarks of cancer allows us to explore carcinogenesis suppression further based on molecular targeted therapy. Kinases, one type of protein involved in signal transduction regulating cell growth and differentiation, could be the proteins that are proposed to be inhibited in suppressing tumor growth. An interesting example of the drug being discovered based on molecular modeling is the discovery of lapatinib as anti- cancer with specific target on HER-2 and EGFR to overcome the resistance of cancer to Herceptin caused by elevated level of EGFR expression.Keywords : targeted therapy, cancer, translational drug development
Combination of Solanum nigrum L. Herb Ethanolic Extract and Doxorubicin Performs Synergism on T47D Breast Cancer Cells Anindyajati Anindyajati; Sarmoko Sarmoko; Dyaningtyas Dewi Pamungkas Putri; Adam Hermawan; 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/indonesianjcanchemoprev1iss2pp78-84

Abstract

Leunca (Solanum nigrum L.) has been proven to possess anticancer activity on some type of cancer cells. In vitro study of solamargine found in the herb showed cytotoxic effect against several breast cancer cell lines, such as T47D and MDA-MB-31. Hence, further study on its potential as a co-chemotherapeutic agent needs to be conducted, in order to overcome resistance problem commonly found in cancer chemotherapy. This study aimed to examine the cytotoxic activity of leunca herb ethanolic extract (LEE) alone and its combination with doxorubicin. Single and combinational treatment of LEE and doxorubicin on T47D breast cancer cells were done, and their viability representing cytotoxicity were analyzed by using MTT assay to determine the IC50 value and combination index (CI) to evaluate the combinational effect. Twenty four hours-treatment of LEE alone gave cytotoxicity activity showing a dose-dependent manner with the IC50 of 47 µg/ml, while combinational treatment showed that 4 µg/ml LEE was found to be synergist with 4 nM doxorubicin on T47D cells, with the optimum CI value of 0.59. This result shows that Solanum nigrum L. is potential to be proposed as doxorubicin co-chemotherapeutic agent against breast cancer. Further study on its molecular mechanism needs to be conducted.Key words: Solanum nigrum, doxorubicin, synergist, breast cancer
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
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
Selectivity of Ethyl Acetate Fraction of Gynura Procumbens on Colon Cancer and Breast Cancer Nunuk Aries Nurulita; Edy Meiyanto; Sugiyanto Sugiyanto
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/indonesianjcanchemoprev2iss3pp274-280

Abstract

Gynura procumbens is widely used as traditional remedy in South-East Asia. Gynura procumbens exhibites anti inflammatory, antioxidant, and reduced blood pressure activity. The aim of this study was to determine chromatographic profile of ethyl acetate fraction of Gynura procumbens (FEG) and to investigate its cytotoxic properties and selectivity to colon cancerand breast cancer cancer cells. The chromatographic profile of FEG was determined using HPTLC densitometric and HPLC. MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine the growth inhibitory effect of FEG on the growth of WiDr, MCF-7, and T47D cells. NIH3T3, a normal cells was used to determine the selectivity of FEG, which contained small amount of quercetin as identified from chromatographic profile both HPTLC and HPLC. FEG inhibited cell growth of WiDr, of MCF-7 and of T47D cells in time dependent manner. Quercetin affected cell growth inhibition approximately two fold higher at WiDr and MCF-7, whereas FEG had lower effect on T47D cell. Quercetin did not seem as the main active compound of FEG. At this study, FEG caused less inhibition on the growth of NIH3T3 cells than that of on all cell lines. Selectivity index (SI) of FEG on WiDr, MCF-7 and T47D were 4.97, 2.77 and 7.79 respectively. According to the datas obtained, FEG possesses moderate to high cytotoxicity properties on WiDr, MCF-7 and T47D cells. FEG demonstrates selective effect against cancer cells and reveals prospective properties as cancer chemoprevention agent.Keywords: Gynura procumbens, colon cancer, breast cancer, cytotoxicity, selectivity
Synergistic Effect of Cinnamon Essential Oil (Cinnamomum burmannii) and Doxorubicin on T47D Cells Correlated with Apoptosis Induction Etyk Yunita Anjarsari; Nita Kristina; Yonika Arum Larasati; Dyaningtyas Dewi Pamungkas Putri; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 4, No 1 (2013)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev4iss1pp450-456

Abstract

Cinnamon  (Cinnamomum burmannii)  shows  anticancer activity  in  several  types  of  cancer  cells.  The aim of this study is to  observe the  cytotoxic  activity  of  cinnamon essential oil (CEO) solely and its combination with doxorubicin,  also the  ability  of  the  combination to induce apoptosis on T47D breast cancer cells. The CEO was prepared through distillation of dry cinnamon bark. Cytotoxic  assay  was performed by using MTT assay and apoptosis determination was done by using double staining with ethidium bromide and acridine orange. The result showed that CEO exhibited cytotoxic effect on T47D cells with IC50 values of 75 µg/ml.  Moreover, CEO showed synergist effect with doxorubicin. The lowest combination index (CI) with CI values of 0,37 was obtained by combination of doxorubicin-CEO  37,5  µg/ml-1,25  µM.  Treatment with CEO solely and its combination with doxorubicin showed apoptosis induction on T47D cells. The results of this  study  indicate  the potency of CEO  to  be  developed  as co-chemotherapeutic  agent  of  doxorubicin on breast cancer. Keywords:  cinnamon essential oil, doxorubicin, T47D cells, combination cytotoxic
Leunca (Solanum nigrum L.) Herbs Ethanolic Extract Increase Cytotoxic Activity of Cisplatin on Hela Cervical Cancer Cells Raditya Prima Istiaji; Maya Fitria; Larasati Larasati; Fortunella Tjondro; Astrid Ayu Maruti; Erna Prawita Setyowati; 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/indonesianjcanchemoprev1iss1pp32-37

Abstract

Cervical cancer is one of leading causes of cancer death in women in the developing countries. The use of cisplatin as chemotherapy agent in cervical cancer is known to cause side effects and also resistance for long-term uses. One of the strategies to prevent cervical cancer based on combination agents is being developed. Leunca (Solanum nigrum L.) has been revealed to inhibit growth of human cancer cells. Therefore, it can be used in combination with cisplatin to reduce those side effects and prevent the occurrence of cell resistance. Ethanolic extract of Leunca Herb (ELH) and cisplatin were tested their cytotoxic effect on HeLa cervical cancer cell by using MTT assay to determine IC50 value. The combinationss of cisplatin-ELH were tested to determine the combination index (CI value). The IC50 of ELH and cisplatin on HeLa cells were 227 µg/mL and 17 µM. rRespectively. Tthe study of combination resulted that almost all the index combinations were <0,9 showed the effect of synergism combination. The Ooptimum concentration of combination was 1/8 IC50 cisplatin–1/8 IC50 ELH. The results indicated that ELH had a potency to be combination agent to enhance the activity of cisplatin on HeLa cervical cancer cells. Therefore, further study on its molecular mechanism needs to be explored. Key words: Leunca (Solanum nigrum L.), cisplatin, cytotoxic, combination agent, HeLa cells
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
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