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Ethanolic Extract of Moringa oleifera L. Increases Sensitivity of WiDr Colon Cancer Cell Line Towards 5-Fluorouracil Nur, Kholid Alfan; Putri, Herwandhani; Cahyani, Fany Mutia; Katarina, Aulia; Susidarti, Ratna Asmah; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Research Gateway

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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 ofÃÂ Moringa oleiferaÃÂ 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 MTTÃÂ assay, and based on apoptosis observation via the double staining method using acrydin orange Ã¢â¬â ethidium bromide (AE) as the staining reagent.Cytotoxicity evaluation of single treatment using concentrations of 5, 20, 50, 100,125, and 250 ÃÂµg/ml of MEE reduced cell viability 24 hours post-treatment. 5, 50, and 250 ÃÂµg/ml of MEE was chosen as the combination concentrations with 1000 ÃÂµM 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 agentÃÂ by increasing the sensitivityÃÂ of WiDr colon cancer cell line towards 5-FU.

Ethanolic Extract of Mangosteen (Garcinia mangostana) Peel Inhibits T47D and Hela Cells Line Proliferation Via Nf-kB Pathway Inhibition Rivanti, Erlina; Rohmah, Annishfia Lailatur; Putri, Herwandhani; Tirtanirmala, Prisnu; Pamungkas, Dyaningtyas Dewi Putri
Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Research Gateway

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Effective and selective chemoterapeutic and chemopreventive agent is needed to cure breast and cervical cancers. One of the potential natural material is mangosteen peel (Garcinia mangostana). In this study, we observed cytotoxic effect of ethanolic extract of mangosteen peel (EMP) on HeLa cells line and T47D cells line. The cytotoxic effect was determined using MTT assay. EMP showed cytotoxic effect on T47D cells and HeLa cells with IC50 values of 2.07 Î¼g/ml and 10.58 Î¼g/ml respectively. Molecular docking simulation was done to predict the molecular mechanism of active compund in mangosteen peel extract, Î±-mangostin, in NFÎºB pathway which is one of the potential pathway to induce cytotoxicity on T47D and HeLa cells. Docking was done using PLANTS software and the binding score betweenÂ Î±-mangostin and proteasom is -78,12, whereas the binding score betweenÂ Î±-mangostin and IKK is -86.84. These results showed the possiblity mechanism of mangostin peel extract containingÂ Î±-mangostin inhibits IKK activation in NFÎºBÂ pathway. Based on this study, we conclude that mangosteen peel extract is potential to be developed as chemopreventive agent toward cervical and breast cancers.Keywords : Mangosteen peel (Garcinia mangostana), cytotoxic, T47D cells, HeLa cells,Â NFÎºB

The Selectivity of Ethanolic Extract of Buah Makassar (Brucea javanica) on Metastatic Breast Cancer Cells Sutejo, Ika Rahmawati; Putri, Herwandhani; Meiyanto, Edy
Journal of Agromedicine and Medical Sciences Vol 2, No 1 (2016)
Publisher : Medical Faculty of Jember University (Fakultas Kedokteran Universitas Jember)

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Treatment of cancer such as surgery, radiotherapy and chemotherapy has many side effects. Chemopreventive agent is needed to reduce the side effect and increase the effectivity of therapy. The discovery ofÂ cochemopreventive agent should consider on its selectivity to reduce side effects. The selective cochemopreventive agents work effectively in cancer cells and safe for normal cells. Buah Makassar (Brucea javanica) is a natural product that is empirically used for anti-inflammatory and antitumor. The purpose of this study is to determine the cytotoxic effect of ethanolic extract of buah Makassar against 4T1, MCF7, HeLa, and Vero cell lines. The cytotoxic test is performed by MTT assay. The parameter obtained from the cytotoxic test was IC50. Selectivity index is determined from IC50 ratio of cancer cells to normal cells. The results showed that ethanolic extract of buah Makassar has a cytotoxic activity on 4T1, MCF7, HeLa, and Vero cells with IC50 were 49,9Â±0,83 Î¼g/mL; 107,6Â±8,14 Î¼g/mL; 228,9Â±4,16 Î¼g/mL and 395,5Â± 4,21 Î¼g/mL respectively. It also has high selectivity on 4T1 metastatic breast cancer cell with selectivity index of 7,93. It can be concluded that the ethanolic extract of buah Makassar has potential to be delevoped as cochemopreventive agent especially on metastatic breast cancer. Keywords: Brucea javanica, MTT assay, selectivity index, 4T1, MCF7, HeLa, Vero

SYNERGISTIC COMBINATION OF Curcuma xanthorrhiza, Ficus septica AND DOXORUBICIN INHIBITS METASTASIS OF BREAST CANCER THROUGH INHIBITION MMP-9 ACTIVITY Sutejo, Ika Rahmawati; Putri, Herwandhani; Meiyanto, Edy
UNEJ e-Proceeding 2016: Proceeding of 1st International Conference on Medicine and Health Sciences (ICMHS)
Publisher : UNEJ e-Proceeding

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Breast cancer is one of the most commonmalignancy on woman in Indonesia (Kemenkes RI,2015). Breast cancer patients usually come todoctor in a late stage & the deaths are due to thecomplications of metastasis in vital organs (NationalCancer Institute, 2012). The death case mostprobably happened when cancer is aggresive &distant metastazed. One factor that causingaggresivity & metastasis is presence of HER2 protein.HER2 is found in 25% cases of Ca mammae. Her2status also influences preference of drug for cancertreatment. Besides of antibodi monoklonal &antireseptor of tirosine kinase, doxorubicin is stillused for treatment breast cancer with overexpressHER2 (Nielsen et al., 2009). Long term use ofdoxorubicin causes several side effects, resistanceand toxicity to normal tissues (Smith et al., 2010).Therefore, combining doxorubicin withchemopreventive agent is needed to increaseactivity of doxorubicin, to overcome the drugresistance and to reduce its side effect (Sarkar andLi, 2006). Chemopreventive agent used in thisresearch are temulawak (Curcuma xanthorrhiza) andawar-awar (Ficus septica). The leaves of Ficus septicahave been used to treat colds, fungal and bacterialdiseases, and various cancers. The ethanolic extractof Ficus septica showed a cytotoxic effect on breastcancer T47D cell lines with IC50 value of 13 Î¼g/mL.The extract at 4.88 Î¼g/mL also showed an optimumsynergistic effect in combination with doxorubicin(3.75 nmol) (Pratama et al., 2010). In addition, theextract induced apoptosis and down regulated theexpression of Bcl-2 protein in breast cancer cellsMCF-7 (Sekti et al., 2010). The major components ofC. xanthorrhiza are curcumin and xanthorrhizol.Curcumin suppresses a number of key elements incellular signal transduction pathways pertinent togrowth, differentiation, and malignanttransformation (Kunumakkara et al., 2008). Choi etal. (2005) observed that injection of 0.2-1.0 mg/kgbw xanthorrhizol had an antimetastatic effect in amouse lung metastasis model.It is a general assumption that combinationtreatment is sometimes more beneficial than singlecompounds. The previous study reported thatcombination of doxorubicin and chemopreventiveagent showed synergistic effect in cancer treatment(Lewandowska et al., 2014). The purpose of thisstudy is to prove antimetastasis effect ofcombination of ethanolic extract of rhizome ofCurcuma xanthorrhiza (ECx), ethanolic extract ofleave of Ficus septica (EFs), and doxorubicin solelyand its combination on MCF7-HER2 breast cancercell line through inhibition activity of MMP-9.Cytotoxic assay is used to determine the synergy ofcombinations. Antimetastasis effect was observedthrough inhibition of cancer cell invasion. Gelatinzymography signify the inhibitory activity of MMP-9,which plays an important role in cancer cell invasion.

SYNTHESIS AND CYTOTOXIC ACTIVITY OF 2,5-BIS(4-BORONIC ACID)BENZYLIDINE CYCLOPENTANONE ON HER2 OVEREXPRESSED-CANCER CELLS Utomo, Rohmad Yudi; Putri, Herwandhani; Pudjono, Pudjono; Susidarti, Ratna Asmah; Jenie, Riris Istighfari; Meiyanto, Edy
INDONESIAN JOURNAL OF PHARMACY Vol 28 No 2, 2017
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Development of chemotherapeutic agent and boron carrying pharmaceutical based on HER2 specific targeted is important due to its role in enhancing cancer progression. The purpose of this study is to synthesize curcumin analogue, namely Pentagamaboron-0 (PGB-0) or 2,5-bis(4-boronic acid)benzylidine cyclopentanone, and to explore the cytotoxic activity on HER2 overexpressed-cancer cells. MCF-7/HER2 was used as a model of HER2 overexpressed-cancer cells and NIH3T3 as normal cells. PGB-0 bound to ATP binding site of HER2 and EGFR based on molecular docking study. PGB-0 was synthesized resulting in 33% yield and was confirmed by IR, 1HNMR, 13CNMR and Mass spectroscopy. Based on MTT assay PGB-0 decreased cells viability on MCF-7/HER2 cells with IC50 value of 270 ÂµM but performed no effect on NIH3T3 cells. Cell cycle analysis revealed that PGB-0 increased sub-G1 accumulation. PGB-0 decreased HER2 expression in a dose-dependent manner. We conclude that the new compound PGB-0 inhibits cell growth through cell death induction and decreased HER2 expression. Thus, PGB-0 is potential to be developed as a chemotherapeutic agent and boron carrying pharmaceutical targeted on the HER2 receptor.

ETHANOLIC LEAVES EXTRACT OF AWAR-AWAR (FICUS SEPTICA) AS SELECTIVE CHEMOPREVENTIVE AGENT ON VARIOUS CANCER CELLS Sutejo, Ika Rahmawati; Putri, Herwandhani; Meiyanto, Edy
NurseLine Journal Vol 1 No 2 (2016): Nopember 2016
Publisher : Faculty of Nursing, University of Jember

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Treatment of cancer such as surgery, radiotherapy and chemotherapy have many side effects such as cardiotoxicity, hepatotoxicity, and immunosuppressant, therefore selective cochemopreventive agent is needed.  Awar-awar (Ficus septica) is  a  traditional  medicinal  plant  that  is  known as a potential cancer chemopreventive agent. The purpose of this study was to determine the cytotoxic effect of ethanolic leaves extract of awar-awar (EFs) against 4T1 and MCF7/HER2 breast cancer cells; WIDR colon cells cancer, HeLa cervix cells cancer, and Vero normal cells. The cytotoxic test was performed by MTT assay. The parameter obtained from the cytotoxic test was IC50. Selectivity index was determined from IC50 ratio of cancer cells to normal cells Vero. The results showed that EFs has a cytotoxic activity on cancer cell line with IC50 61,2 Âµg/mL on 4T1; 48 Âµg/mL on MCF7/HER2; 122,4 Âµg/mL on Hela; 75,9 Âµg/mL on WiDR; and 394,8 Âµg/mL on Vero. It can be concluded that  EFs has high selectivity on various cancer cells with selectivity index more than 3.

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

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

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

Ethanolic Extract of Mangosteen (Garcinia mangostana) Peel Inhibits T47D and Hela Cells Line Proliferation Via Nf-қB Pathway Inhibition Rivanti, Erlina; Rohmah, Annishfia Lailatur; Putri, Herwandhani; Tirtanirmala, Prisnu; Putri, Dyaningtyas Dewi Pamungkas
Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Society for Cancer Chemoprevention

Effective and selective chemoterapeutic and chemopreventive agent is needed to cure breast and cervical cancers. One of the potential natural material is mangosteen peel (Garcinia mangostana). In this study, we observed cytotoxic effect of ethanolic extract of mangosteen peel (EMP) on HeLa cells line and T47D cells line. The cytotoxic effect was determined using MTT assay.EMP showed cytotoxic effect on T47D cells and HeLa cells with IC50 values of 2.07 μg/ml and 10.58 µg/ml respectively. Molecular docking simulation was done to predict the molecular mechanism of active compund in mangosteen peel extract, α-mangostin, in NFқB pathway which is one of the potential pathway to induce cytotoxicity on T47D and HeLa cells. Docking was done using PLANTS software and the binding score between α-mangostin and proteasom is -78,12, whereas the binding score between α-mangostin and IKK is -86.84. These results showed the possiblity mechanism of mangostin peel extract containing α-mangostin inhibits IKK activation in NFқB pathway. Based on this study, we conclude that mangosteen peel extract is potential to be developed as chemopreventive agent toward cervical and breast cancers.Keywords: Mangosteen peel (Garcinia mangostana), cytotoxic, T47D cells, HeLa cells, NFқB

Ethanolic Extract of Moringa oleifera L. Increases Sensitivity of WiDr Colon Cancer Cell Line Towards 5-Fluorouracil Nur, Kholid Alfan; Putri, Herwandhani; Cahyani, Fany Mutia; Katarina, Aulia; Susidarti, Ratna Asmah; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Society for Cancer Chemoprevention

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

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