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Ekstrak Etanolik Daun Awar-Awar (Ficus septica Burm F.) secara Sinergis Meningkatkan Efektivitas Doxorubicin terhadap Sel Kanker Payudara T47D PRATAMA, RATIH HARDIKA; IKHTIARSYAH, YURISTA GILANG; ANINDYAJATI, ANINDYAJATI; FITRIASARI, ADTYA; IKAWATI, MUTHI; MEIYANTO, EDY
JURNAL ILMU KEFARMASIAN INDONESIA Vol 9 No 1 (2011): JIFI
Publisher : Fakultas Farmasi Universitas Indonesia

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Daun awar-awar (Ficus septica Burm E), yang belum dimanfaatkan secara optimal dalam pengobatan kanker, memiliki potensi untuk digunakan sebagai agen kombinasi dengan doxorubicin. Penelitian ini bertujuan untuk mengetahui efek sitotoksik ekstrak etanolik daun awar-awar (EDA) dan kombinasinya dengan agen kemoterapi doxorubicin (DOX) pada sel kanker payudara T47D. EDA diperoleh dari maserasi serbuk kering daun awar-awar dengan etanol 70%. Pengujian aktivitas sitotoksik ekstrak dilakukan dengan MT T assay, baik perlakuan tunggal maupun kombinasinya dengan DOX. Sifat sitotoksik ditentukan dengan nilai IC50, sementara efektivitas kombinasi dihitung dengan nilai indeks kombnasi (CI) untuk menetapkan apakah efeknya sinergis, aditif, atau antagonis. Uji sitotoksik perlakuan EDA tunggal selama 24 jam menunjukkan efek sitotoksik yang potensial dengan IC50 sebesar 13 µg/mL. Kombinasi EDA-DOX menunjukkan efek sinergis (CI < 1) pada konsentrasi EDA 4,88 µg/mL dan DOX 3.75 nM. Hasil ini menunjukkan bahwa EDA memiliki potensi yang menjanjikan untuk diaplikasikan sebagai agen ko-kemoterapi DOX pada terapi kanker payudara.

Combination of Leunca Herb Ethanolic Extract and Doxorubicin Suppresses HeLa Cells’ Growth Sarmoko, Sarmoko; Putri, Dyaningtyas Dewi Pamungkas; Puspitasari, Endah; Anindyajati, Anindyajati; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Society for Cancer Chemoprevention

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

Ficus septica Burm. F. Leaves Ethanolic Extract Induces Apoptosis in 7,12-Dimethylbenz[A]Nthracene-Induced Rat Liver Cancer Quatitavely Septhea, Dita Brenna; Anindyajati, Anindyajati; Darma, Andita Pra; Nurzijah, Ika; Nugroho, Agung Endro; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 2, No 2 (2011)
Publisher : Indonesian Society for Cancer Chemoprevention

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

Translational Research in Cancer Drug Development Meiyanto, Edy; Hermawan, Adam; Anindyajati, Anindyajati
Indonesian Journal of Cancer Chemoprevention Vol 2, No 2 (2011)
Publisher : Indonesian Society for Cancer Chemoprevention

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

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

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

Combination of Solanum nigrum L. Herb Ethanolic Extract and Doxorubicin Performs Synergism on T47D Breast Cancer Cells Anindyajati, Anindyajati; Sarmoko, Sarmoko; Putri, Dyaningtyas Dewi Pamungkas; Hermawan, Adam; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Society for Cancer Chemoprevention

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

Ficus septica Burm. f. Leaves Ethanolic Extract Triggered Apoptosis on 7,12-Dimethylbenz[a]anthracene-Induced Rat Mammary Carcinogenesis Qualitatively Anindyajati, Anindyajati; Darma, Andita Pra; Nurjizah, Ika; Septhea, Dita Brenna; Nugroho, Agung Endro
Indonesian Journal of Cancer Chemoprevention Vol 3, No 1 (2012)
Publisher : Indonesian Society for Cancer Chemoprevention

Ficus septica Burm. f. ethanolic extract (FEE) shows cytotoxic effects on several cancer cell lines. Our research aimed to investigate the effect of FEE on apoptosis induction and p53 expression against carcinogenesis of 7,12-Dimethylbenz[a]anthracene (DMBA)-induced rat mammary.The research was conducted by comparing both apoptosis induction and p53 expression in DMBA-induced rats that were treated with FEE against control groups. Cells that undergo apoptosis were visualized by Double Staining method with acridine orange and ethidium bromide, while p53 expression was detected by IHC staining. Double staining results showed increased occurrence of apoptotic cells compared to the control groups. IHC staining of p53 did not show significant difference between treatment and control groups. However, FEE was able to repair morphology of cells undergoing carcinogenesis. Thus, we conclude that FEE has an anti-carcinogenic activity on DMBA-induced rat mammary through apoptosis induction without affecting p53 expression. Therefore, the ethanolic extract of Ficus Septica leaves is a potential chemo-preventive agent on breast cancer. Further study on its molecular mechanism needs to be explored.Keywords: Ficus septica, breast cancer, 7,12-Dimethylbenz[a]anthracene, carcinogenesis, apoptosis, p53

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