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Hesperidin increase cytotoxic effect of doxorubicin in MCF-7 cells Adam Hermawan
Indonesian Journal of Pharmacy Vol 21 No 1, 2010
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (3762.688 KB) | DOI: 10.14499/indonesianjpharm0iss0pp8-16

Abstract

Hesperidin, a flavonoid, shows strong cytotoxic effect in several cancer cell lines. The aim of this research was to investigate cytotoxic activities of hesperidin alone and in combination with doxorubicin. Cell viability assay of hesperidin, doxorubicin, and combination treatments were carried out by using MTT assay. Apoptosis assay was done using double staining method using Ethidium Bromide-Acridine Orange. Hesperidin did not show cytotoxic effect          but doxorubicin showed cytotoxic effect with IC50 467 nM. Hesperidin (5, 50 and  100 µM) increased cytotoxic effect of doxorubicin compared with doxorubicin alone. The strongest cytotoxic activity was showed by the combination of 200 nM doxorubicin and 100 µM hesperidin. Combination treatment of doxorubicin 200 nM and hesperidin 100 µM induced apoptosis in MCF-7 cells. Hesperidin is potentially to be developed as co-chemotherapeutic agent for breast cancer, while molecular mechanism need to be explored.  Key words: Hesperidin, doxorubicin, synergism, MCF-7, apoptosis
Combination of Tangeretin and 5-Fluorouracil Modulates Cell Cycle and Induce Apoptosis on WiDr Cells Luthfia Indriyani; Adam Hermawan; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 3, No 1 (2012)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev3iss1pp364-369

Abstract

Co-chemotherapeutics approaches are increasing in cancer treatment in order mainly to suppress the resistence phenomenon of cancer treatment and to enhance the cytotoxic effect of the main chemotherapeutics agent. Tangeretin has been known to have cytotoxic effect to some cancer cells through some pathways in the cells. To explore the potential effect of tangeretin as co-chemotherapeutics agent this research was subjected to study the cytotoxic effect of tangeretin in combination with 5-Fluoro Uracil (5-FU) on WiDr colon cancer cells covering the modulation of cell cycle and apoptosis induction. Cytotoxic effect was examined by using MTT assay while apoptotis induction was determined by annexin-V flowcytometry. Under MTT assay, tangeretin showed weak cytotoxic activity on the cells. However, tangeretin significantly enhanced the cytotoxic effect of 5-FU on the cells. This co-chemotherapeutics effect likely correlated with cell cycle modulation effect, especially in inducing polyploidy phenomenon as expressed in the flowcytometric graph of the DNA content. This combination also increased apoptosis induction. These result suggest that tangeretin is potential to be developed as co-chemotherapeutic agent for 5-Fu on colon cancer and further molecular mechanism need to be explored.Keywords: Tangeretin, 5-Fluorourasil, WiDr, cell cycle, apoptosis.
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
Heartwood of Secang (CAESALPINIA SAPPAN L.) Ethanolic Extract Show Selective Cytotoxic Activities on T47D and Widr Cells But Not on Hela Cells Erlina Rivanti; Bani Adlina Shabrina; Ika Nurzijah; Cyndwika Ayu; Adam Hermawan
Indonesian Journal of Cancer Chemoprevention Vol 7, No 2 (2016)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev7iss2pp60-67

Abstract

The present study investigate the selectivity of heartwood of secang ethanolic extract (SEE) on T47D breast cancer cells, WiDr colon cancer cells, and HeLa cervical cancer cells, compared to Vero normal epithelial cells. The cytotoxic effect was evaluated by using MTT assay  with 24-hour treatment to get IC50values. Selectivity was evaluated by using selectivity index (SI). SEE had a potent cytotoxic activity on T47D and WiDr cancer cells (IC50 <100 µg/ml). IC50 value of HeLa cancer cells was observed on moderate cytotoxic (100 <IC50 <1000 µg/ml). SEE demonstrated more selective to T47D and WiDr than Vero cells (SI > 3), while in HeLa cells is not selective (SI < 3). This result indicating its potential of Caesalpinia sappan as a chemopreventive agent in cancer therapy.Keywords: Cancer, selectivity, Secang, T47D, WiDr, HeLa, Vero
Anti-metastatic Activity of Curcumin Analog Pentagamaboronon-0-Sorbitol Against HER2-overexpressed MCF-7 Breast Cancer Cells Lailatul Qodria; Indah Hairunisa; Rohmad Yudi Utomo; Adam Hermawan; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 9, No 3 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev9iss3pp118-125

Abstract

Breast cancer with Human Epidermal Growth Factor Receptor (HER)2 overexpression increases tumor progession and lead to metastasis, which is primarily cause of mortality in breast cancer. Pentagamaboronon-0 Sorbitol (PGB-0-So) is an aquoeous formulation of curcumin analog, PGB-0, with sorbitol. This compound has been developed as an anti-cancer chemotherapeutic agent and a boron carrying pharmaceutical for boron neutron capture therapy (BNCT). The aims of this study are to investigate antimetastatic activities of PGB-0-So against HER2-overexpressed MCF-7 breast cancer (MCF-7/HER2) cells. The MTT cytotoxicity assay of PGB-0-So exhibited cytotoxic effect with an IC50 value of 35 μM. The testing of anti-migration activity using the scratch wound healing assay demonstrated that PGB-0-So inhibited the closure of the wound on MCF-7/HER2 cells compare to the control. Furthermore, PGB-0-So was able to suppress matrix metalloproteinase (MMP)-9 activities, based on the gelatin zymography assay. In conclusion, PGB-0-So has potency to be developed as an anti-cancer agent against metastatic breast cancer.Keywords : PGB-0-So, anti-metastatsis, cell migration, MMP-9, MCF-7/HER2
Structure Modification of Ethyl p-methoxycinnamate Isolated from Kaempferia galanga Linn. and Citotoxicity Assay of The Products on WiDr Cells Juni Ekowati; Marcellino Rudyanto; Shigeru Sasaki; Tutuk Budiati; Sukardiman -; Adam Hermawan; 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/indonesianjcanchemoprev1iss1pp12-18

Abstract

Ethyl p-methoxycinnamate, major ingredient of Kaempferia galanga rhizome, have been reported not only has analgesic – anti inflammatory activities like NSAIDs which inhibited cyclooxygenase, but also inhibit tumor cell proliferation in specimen of mouse epidermis. Therefore, it will be interesting to carry out synthetic studies on the derivates of ethyl p-methoxycinnamate and searching their citotoxic activity on WiDr cell. We wish to report of structure modification on carboxyl moiety of ethyl p-methoxycinnamate  and  evaluation on their citotoxic activity  on WiDr cell. Isolation of ethyl p-methoxycinnamate from Kaempferia galanga rhizome was carried out by percolation with ethanol 96% as solvent. Hydrolysis of ethyl p-methoxycinnamate in basic condition was performed to obtain p-methoxycinnamic acid. Preparation of some thiourea derivates of ethyl p-methoxycinnamate was carried out  by microwave irradiation. Citotoxicity assay was carried out by MTT method for 48 h.Modification of carboxyl group of ethyl p-methoxycinnamate to its thiourea form could be carried out by microwave irradiation gave; (E)-3-(4-methoxyphenyl)-N-(phenylcarba- mothioyl)acrylamide (50%); (E)-3-(4-methoxyphenyl)-N-(4-methoxyphenylcarbamothi- oyl)acrylamide (26%) and (E)-3-(4-methoxyphenyl)-N-(4-methylphenylcarbamothioyl) acrylamide (54%), yield calculated for 2 step from the acid chloride. All compounds showed no citotoxic effect on WiDr cell at 48 h incubation.Keywords :  ethyl p-methoxycinnamate, microwave irradiation, Kaempferia galanga, citotoxicity, WiDr cell
Hesperidin Increases Cytotoxic Effect of 5-Fluorouracil on WiDr Cells Yurista Gilang; Adam Hermawan; Aditya Fitriasari; Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev3iss2pp404-409

Abstract

Therapy of colon cancer by using 5-FU often causes problems of resistance. This encourages the development of co-chemotherapy agent. One of the compounds that could potentially be used as a co-chemotherapy agent is hesperidin. This study was conducted to determine the cytotoxic effects of hesperidin, 5-FU and the combination of them, as well as apoptosis induction in colon cancer cells WiDr. Cytotoxic effect of hesperidin, 5-FU, and its combination were observed using MTT assay. Observation of apoptosis was done by double staining method using ethidium bromide-acridin orange. Until 48 hours incubation, hesperidin showed no cytotoxic effects. Cytotoxic effects of 5-FU was observed after 48 hours with the IC50 value of 422 µM. However, hesperidin improved the cytotoxic effects of 5-FU at 48 hour incubation. Either single treatment of hesperidin 200µM or 5-FU 1500 µM did not trigger apoptosis, but combination of them led to the emergence of signs of apoptosis. Based on this study,it can be concluded thathesperidin is potential to be developed as a co-chemotherapy agent of 5-FU on colon cancer but still need further study on its molecular mechanisms.Keywords : hesperidin, 5-fluorouracil, WiDr cells, cytotoxic, apoptosis
The Cytotoxic Activity of Solanum Nigrum Ethanolic Extract on Widr Human Colon Cancer Cells Astrid Ayu Maruti; Ilham Augusta F.; Dyaningtyas Dewi Pamungkas Putri; Adam Hermawan; Muthi&#039; Ikawati
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/indonesianjcanchemoprev2iss3pp291-294

Abstract

Solanum nigrum L. or Leunca in Indonesia has been traditionally used as a herbal plant, which is believed to have anti-tumor properties, although the mechanism for the activity remains unknown. The resecarch aim to examine the cytotoxic effect of the ethanolic extract of Solanum nigrum on WiDr human colon cancer cells. In this study, we prepared an ethanol extract from herb of Solanum nigrum and investigated the mechanism involved in its growth-inhibitory effect on WiDr human colon cancer cells. Herbs of Solanum nigrum dry powder is extracted with 70% ethanol then added into the WiDr cell culture in 96 wells plate in various concentration : 50, 100, 250, and 500 µg/ml. Cytotoxicity of the Solanum nigrum ethanolic extract  was analyzed with MTT assay on WiDr human colon cancer cell lines. Results from the MTT assay showed WiDr cells was weakly suppressed in the presence of the extract. The result of the assay also showed a very close correlation between the Solanum nigrum extract concentration and the surviving cell numbers which means the extract caused cell death in a dose-dependent fashion in WiDr cancer cells with the IC50 of 359,23 µg/ml. Collectively, the research suggest further studies to explore other chemopreventive possibilites of Solanum nigrum ethanolic extract.Keywords : colon cancer, MTT assay, cytotoxic, WiDr, Solanum nigrum
Curcumin Analog Pentagamaboronon-0-Sorbitol Inhibits Cell Migration Activity of Triple Negative Breast Cancer Cell Line Ratna Dwi Ramadani; Rohmad Yudi Utomo; Adam Hermawan; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 9, No 3 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev9iss3pp126-133

Abstract

Mortality in cancer is primarily due to failure of metastasis prevention. One strategy to target the cancerous cell is Boron Neutron Captured Therapy which showed high affinity toward cancer cells and reported to have anti-proliferative as well as antimetastatic activities. Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada, has developed boron-containing substance namely pentagamaboronon-0 (PGB-0) which is known to exhibit anticancer activity towards breast cancer cell. The purposes of this research are focused to explore the anti-migratory activities of PGB-0-So against triple negative breast cancer cell. The MTT cytotoxicity assay of PGB-0-So against 4T1 breast cancer cell line were found to exert potential effect in dose-dependent manner with IC50 values of 39 μM. The study of cell migration inhibition using in vitro wound healing assays and gelatin zymography on highly metastasis breast cancer cell line 4T1, following the treatment of sub IC50 doses of PGB-0-So complex slightly inhibited cell migration through the inhibition of matrix metalloproteinase-9 expression. These findings suggest that PGB-0-So is potential as an anticancer agent.Keywords : curcumin analogue, PGB-0-So, 4T1 Cells, migration, MMP-9 
Ursolic Acid Enhances Doxorubicin Cytotoxicity on MCF-7 Cells Mediated by G2/M Arrest Ibrahim Arifin; Adam Hermawan; Muthi&#039; Ikawati; Sari Haryanti; Anindyajati Anindyajati; Edy Meiyanto
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
Co-Authors . Anindyajati . Larasati Adisusilo, Midori Rahmadhany Putri Aditya Fitriasari Aditya Fitriasari Agusta Fauzi, Ilham Agustina Setiawati Al-Qorin, Fadillah Amaliyatul, Mita Ameilinda Monikawati Andita Pra Darma Angraini, Sonia Meta Anindyajati Anindyajati Anindyajati Anindyajati Arya Nugraha, Reyhan Asep Nuryadin Astrid Ayu Maruti Astrid Ayu Maruti Azmi Rahmadani Bambang Sulistiyo Ari Sudarmanto Bani Adlina Shabrina Cyndwika Ayu Dewi Pratiwi Dewi Pratiwi Dhania Novitasari Dini Maharani Dyaningtyas D. P. Putri Dyaningtyas D.P. Putri Dyaningtyas Dewi Putri Pamungkas Ediati Sasmito Ediati Sasmito Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Erlina Rivanti Esti, Yuni Fajar Fauziyah Darwis, Rattu Syahada Fazri, Rezi Muhammad Fikri Amalia Guntara, Rangga Gelar Handani, Dewa Ayu Sri Heny Hendrayati Herwandhani Putri Ibrahim Arifin Ika Nurzijah Ikawati, Muthi' Ilham Agusta Fauzi Ilham Augusta F Ilham Augusta F. Indah Hairunisa Indri Kusharyanti Inna Armandari Jenie, Riris Istighfari Juni Ekowati Kartika Dyah Palupi Kartika Dyah Palupi Khairunnisa, Najla Laeli Muntafiah Lailatul Qodria Lailatul Qodria Larasati Larasati Luthfia Indriyani Luthfia Indriyani Maesaroh, Syti Sarah Maran, Gergorius Gena Marcellino Rudyanto Maulid, Zaki Nuraziz Meiyanto, Edy Mokh Adib Sultan, Mokh Adib Muhammad Novrizal Abdi Sahid Musyaffa, Fakhrizal Labib Muthi Ikawati Nanda Resa Pratama Nanda Resa Pratama Naufa Hanif Niken Nur W Niken Nur W, Niken Novi Hastuti Novi Hastuti, Novi Nugraha, Muhammad Rizki Nugraheni, Nadzifa Nur Fitra Sari Nurhaliza, Jelita Nurma Sabila Nurrachma, Marsya Yonna Perdana Adhi Nugroho Pratama, Dimo Purwaamijaya, Btari Mariska Putri, Nindya Budiana Rahmawati, Desty Restia Rahmi Khamsita Rahmi Khamsita Ramadani, Ratna Dwi Ratih Hurriyati Ratna Asmah Susidarti Ratna Asmah Susidarti Ratna Dwi Ramadani Retno Murwanti Ridlo, Muhammad Dzikri Ar Riris Istighfari Jenie Riris Istighfari Jenie Riris Istighfari Jenie Rita Riata Rita Riata Ritmaleni, Ritmaleni Rohmad Yudi Utomo Rosana Anna Ashari, Rosana Anna Rumiyati Rumiyati Sahid, Muhammad Novrizal Abdi Santoso, Christopher Filando Sari Haryanti Sari Haryanti Sarmoko Sarmoko Sendy Junedi Shigeru Sasaki Shigeru Sasaki Sofa Farida Sofa Farida Sukardiman Susi Ari Kristina Susi Ari Kristina Susi Ari Kristina Susi Ari Kristina Tamara, Agra Fadhilla Tutuk Budiati Yanti, Septi Dwi Yullia Febrianti, Sheilla Yurista Gilang Yurista Gilang Zahra, Nasywa