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Geometric Isomers and Cytotoxic Effect On T47D Cells of Curcumin Analogues PGV-0 and PGV-1 Edy Meiyanto; Muhammad Da'i; Supardjan A. M.; Umar Anggara Jenie
Indonesian Journal of Pharmacy Vol 18 No 1, 2007
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (343.101 KB) | DOI: 10.14499/indonesianjpharm0iss0pp40-47

Abstract

Curcumin analogues 2,5-bis-(4’-hidroxy-3’-methoxy)-benzilidinecylopentanone (PGV-0) and 2,5-bis-(4’hidroxy-3’,5’-dimethyl)-benzilidinecylopentanone (PGV-1) have a potency to be developed as cytotoxic agent. The aims of this research are to elucidate the geometric isomer and to study the cytotoxic effect on T47D cells of both compounds. To establish the geometric isomer these compounds, they were elucidated by LC-MS, 1H-NMR, 13C-NMR, HMBC, HMQC, NOESY. Their cytotoxic effect were evaluated by MTT assay method on T47D cells. The results concluded that the geometric isomer of PGV-1 is zusammen-zusammen (Z-Z) and PGV-0 is entgegen-entgegen (EE). The IC50 of both compounds are 1.74 and 9.39 μM respectively.Key words: PGV-0, PGV-1, Cytotoxicity
PGV-1 is a potent antimitotic agent Barinta Widaryanti; Edy Meiyanto; Muhammad Da'i; Masashi Kawaichi
Indonesian Journal of Pharmacy Vol 19 No 3, 2008
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (266.103 KB) | DOI: 10.14499/indonesianjpharm0iss0pp145-150

Abstract

Carcinogenesis can be involved in the malfunctioning of programmed cell death Most of the anticancer drug in current use induce apoptosis in susceptible cells. The fact that disparate agent interacting with different targets seem to induce cell death through some common mechanism suggest that anticancer activity is determined by the ability of inhibiting cell growth.Pentagamavunon-1 (PGV-1) is one of the curcumin analogue which showed to have potency in inhibiting proliferation of human breast carcinoma cell T47D. The effect on T47D growth is associated with cell cycle arrest in G2/M phase at the concentration of 2.5 mM, followed by hyperploidy. Our data on polymerization assay, indicate PGV-1 interact with tubulin in different manner from taxol. PGV-1 inhibit tubulin polymerization on cell culture while taxol stabilized tubulin polymerization. Immunostainning data on cell treated with PGV-1 showed slightly tubulin condensation, while cell treated with taxol showed tubulin condensation distinctly at 12 minutes after releasing from depolymerization agent.In conclusion, PGV-1 represent a new microtubule inhibitor and has the potential to be developed for anticancer drugKey words: Pentagamavunon-1, T47D, tubulin, antimitotik
PGV-1 decreases angiogenic factor (VEGF and COX-2) expression on T47D cell induced by estrogen Meiyanto, Edy; Melannisa, Rosita; Da'i, Muhammad
Indonesian Journal of Pharmacy Vol 17 No 1, 2006
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (326.278 KB) | DOI: 10.14499/indonesianjpharm0iss0pp1-6

Abstract

Breast cancer is the most common cancer occurring in women after cervix cancer in Indonesia. Tumor metastasis is the major cause of mortality in breast cancer. For a tumor cell to metastasize effectively, it must induce angiogenesis. 17 β-estradiol has been shown to stimulate the proliferation and angiogenesis of breast cancer cells which express estrogen receptor (ER), T47D (human breast cancer cell line). In the present study Pentagamavunon-1 or PGV-1 [2,5-bis-(4’-hydroxy-3’,5’-dimethylbenzylidene)-cyclopentanone], an analogue of curcumin [1,7-bis-(4’-hydroxy-3’-methoxyphenyl)-1,6-heptadiena-3,5-dion], were tested on their cytotoxicity and suppression effect on angiogenic factors (i.e. VEGF and COX-2) on the breast cancer cell lines (T47D) induced by 17 β-estradiol 10-8 M. The results showed that PGV-1 performed cytotoxicity effect againts T47D cells with IC50 values 3,16 μM. This was more potent than curcumin (IC50 = 19,05 μM). PGV-1 5 μM and curcumin 20 μM decrease VEGF and COX-2 expression. These results suggest both compounds possessed antiangio-genic potensial.Key words : PGV-1, curcumin, 17 β-estradiol, angiogenesis
Cytotoxic Effect of Jati Belanda Leaves towards Cancer Cell Lines Muhammad Da'i
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/indonesianjcanchemoprev6iss2pp35-41

Abstract

The initial research of Jati Belanda leaves extract (JBE) showed the inhibition of breast cancer cell growth (T47D). The phytochemistry screening showed that JBE contain flavonoid, alkaloid, polifenol, and volatile oil. The development of anticancer drugs need the molecular mechanism investigation in order to produce cancer-targeted drugs. The objective of this research is to determine the molecular mechanism of JBE cytotoxicity effect towards cancer cell lines. This research began with cytotoxicity asssay in vitro of JBE towards some cancer cell lines by MTT method. JBE was given in some variety of concentration. The result of this study showed that JBE do not contain tirosid, and contain flavonoid in the concentration of 0,976%. The result of cytotoxicity assay towards MCF-7, HeLa, T47D and Vero showed IC50 value 36,50; 58,02; 53,36; 1806,22 dan 2451,65 µg/mL respectively. It is concluded that JBE have a strong potency to inhibit the growth of WiDr cancer cell line.Keywords : jati belanda, T47D cells, cytotoxicity
Potency of Radical Scavenging Activity and Determination of Total Phenolic Content of Five Ethanolic Extract of Rhizome Zingiberaceae Family Muhammad Da'i; Didiek Setiawan; Rosita Melannisa
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/indonesianjcanchemoprev4iss1pp457-462

Abstract

Several studies show that some plants and fruits could protect human body from free radical danger exposure. Zingiberaceae family has some chemical substances that have antiradical activity, such as phenolic compound and flavonoid. The aim of this study is to determine the correlation of total phenolic compound towards its antiradical activity. Antiradical activity assay was determined by DPPH method (1,1 difenil-2-pikrilhidrazil). The total phenolic compound is determined by spectrofotometry using Folin-Ciocalteu reagent and counted as GAE (Gallic Acid Equivalent). Based on this study, the total phenolic concentration of ethanolic extract of jahe (Zingiber officinale (L.) Rosc), kencur (Kaemferia galanga L.), lengkuas (Languas galanga), lempuyang gajah (Zingiber littorale) and lempuyang pahit (Zingiber americana) is 73.99 mg/g; 23.848 mg/g; 37.841 mg/g; 49.725 mg/g and 40.802 mg/g respectively. The radical scavenging activity (IC50) of jahe (27.38 µg/mL), lengkuas (93,27 µg/mL), lempuyang pahit (105,08 µg/mL), meanwhile lempuyang gajah and kencur show low activity of radical scavenging.Keywords: Zingiberaceae, total phenolic compound, antiradical, DPPH
PENTAGAMAVUNON-1 MENGHAMBAT SIKLUS SEL T47D TERINDUKSI CASPASE INHIBITOR Z-VAD-Fmk PADA FASE G2-M Daâ??i, Muhammad; A.M., Supardjan; Jenie, Umar Anggara; M, Kawaichi; Meiyanto, Edy
Jurnal Farmasi Indonesia Vol 5, No 4 (2011)
Publisher : Jurnal Farmasi Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.35617/jfi.v5i4.54

Abstract

Previous experiment indicated Curcuminâ??s analogue Pentagamavunon-1 (2,5-bis(41-hidroxy-31,51-dimethyl)-benzilidine-cyclopentanone) has inhibitory activity on T47D cell proliferation through induction of apoptosis and cell cycle arrest at G2-M phase. This research was conducted to observe the relationship between the induction of apoptosis and inhibition of cell cycle in T47D cells induced by Pentagamavunon-1 (PGV-1). The T47D cells were treated with 2.5 PGV-1 mM; Z-VAD-Fmk 2.5 mM; (Z-VAD-Fmk 2.5 mM+PGV-1 2.5 mM). Kinetics of cell proliferation was observed with flowcytometer analysis, molecular expression was observed with Western blot methods. The results showed induction of PGV-1 and Z-VAD-Fmk stimulate the accumulation of cells in G2-M phase (39.28%), did not differ significantly with cells that  induced by PGV-1 only (34.19%). Molecular analysis showed that treatment with (PGV-1+Z-VAD-Fmk) could prevent apoptosis through inhibition of activation of Caspase-3, increased the expression of p21 and activated Cdc-2. Overall the study showed inhibition of cell cycle at G2M phase by PGV-1 compound is not affected by the activation of caspase-3. ABSTRAK Analog kurkumin Pentagamavunon-1  (2,5-bis(41-hidroksi-31,51-dimetil)-benzilidinsiklo-pentanon) telah diteliti dapat menghambat proliferasi sel melalui mekanisme induksi apoptosis dan cell cycle arrest pada fase G2-M. Penelitian ini dilakukan untuk mengamati keterkaitan antara proses induksi apoptosis dan penghambatan siklus sel pada sel T47D yang diinduksi senyawa Pentagamavunon-1 (PGV-1). Sel T47D diberi perlakuan PGV-1 2,5 mM; Z-VAD-Fmk 2,5 mM dan (Z-VAD-Fmk 2,5 mM+PGV-1 2,5 mM). Kinetika proliferasi sel diamati dengan analisis flowcytometric, ekspresi molekuler diamati dengan metode Western blot. Hasil pengamatan menunjukkan induksi (PGV-1+Z-VAD-Fmk) memacu akumulasi sel pada fase G2-M (39,28%) tidak berbeda signifikan dengan sel yang hanya diinduksi PGV-1 (34,19%). Pengamatan molekuler menunjukkan perlakuan (PGV-1+Z-VAD-Fmk) mencegah terjadinya apoptosis melalui penghambatan aktivasi Caspase-3. Secara keseluruhan penelitian menunjukkan penghambatan siklus sel pada fase G2-M oleh senyawa PGV-1 tidak tergantung oleh aktivasi Caspase-3.
EFEK SITOTOKSIK EKSTRAK TANAMAN KELADI TIKUS (Typhonium divaricatum (L.) TERHADAP SEL HeLa Daâ??i, Muhammad; Fiveri, Anis; Meiyanto, Edy
Jurnal Farmasi Indonesia Vol 3, No 4 (2007)
Publisher : Jurnal Farmasi Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.35617/jfi.v3i4.86

Abstract

Cervic cancer is the most cancer that suffered by women in the world include in Indonesia. The main purposes of this experiment is to explore the Indonesian plan to find new anticancer agent. This experiment exhibit the cytotoxic effect of (Typhonium divaricatum (L.) Decne) on HeLa cells line. This experiment also directed to know the corelation phenolic content with the cytotoxic effect of extracts Typhonium divaricatum. The result indicated ethyl acetate extract had the best potency as cytotoxic agent compared with ethanol and cloroform extract based on MTT method. The IC50 value of ethil acetate extract was 147,77 μg/ml, chloroform extract was 903,44 μg/ml (based on the extrapolation). Ethanol extract was not resulted the IC50 value. Phenol content in each extracts was resulted by Folin-Ciocalteu method. Total phenol content of ethyl acetate, ethanol and chloroform extracts were 13.154; 12.028; 2.872 mg/g extract respectively. Those results indicate there is no corelation between total phenol content and cytotoxic effect direcly of each extracts. ABSTRAK Kanker leher rahim adalah kanker yang banyak diderita wanita diseluruh dunia, termasuk di Indonesia. Selama ini terapi kanker dengan kemoterapi belum memperoleh hasil yang memuaskan. Penelitian ini dilakukan untuk mendapatkan bahan obat dari alam sebagai antikanker dari tanaman Indonesia. Penelitian ini dilakukan untuk menentukan efek sitotoksik keladi tikus (Typhonium divaricatum (L.) Decne) pada sel kanker leher rahim (sel HeLa) dan diarahkan pula untuk mengetahui korelasi kandungan senyawa fenolik terhadap potensi sitotoksisitas ekstrak tanaman keladi tikus. Hasil uji sitotoksik terhadap sel HeLa, ekstrak etil asetat memiliki efek sitotoksik terbesar terhadap sel HeLa dibanding ekstrak kloroform dan etanol. Nilai IC50 ekstrak etil asetat adalah 147,77 μg/ml, kloroform sebesar 903,44 μg/ml (hasil ekstrapolasi), sedangkan harga IC50 ekstrak etanol tidak dapat ditentukan. Penetapan kadar fenol total dalam masing-masing ekstrak ekstrak tanaman keladi tikus diperoleh dengan penyari etil asetat (13,154 mg/g ekstrak) > etanol (12,028 mg/g ekstrak) > kloroform (2,872 mg/g ekstrak). Hasil-hasil tersebut menunjukkan kandungan senyawa fenolik bukan merupakan penanda utama potensi sitotoksik suatu ekstrak.
Selectivity Index of Alpinia galanga Extract and 1’-Acetoxychavicol Acetate on Cancer Cell Lines Muhammad Da'i; Khairunnisa Azani Meilinasary; Andi Suhendi; Sari Haryanti
Indonesian Journal of Cancer Chemoprevention Vol 10, No 2 (2019)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev10iss2pp95-100

Abstract

Previous research stated that galangal (Alpinia galanga) extract has a potential as cytotoxic agent with active compound of 1’-Acetoxychavicol Acetate (ACA). The objective of this study was to determine the selectivity of ethanol extract, ethyl acetate fraction, and methanol fraction of of galangal, and ACA on cancer cell lines. Cytotoxic activity was carried out using the MTT method on T47D breast cancer, WiDr colon cancer, HeLa cervical cancer, and Vero normal cell lines. The results showed that galangal ethanol extract and its fractions had selectivity index equal to or less than 2 on cancer cells. Meanwhile, ACA had selectivity index more than 3 on T47D cell and HeLa cell. ACA showed a strong cytotoxic activity against cancer cells T47D, HeLa, and WiDr with IC50 values of 3.14, 7.26, and 12.49 μg/ml, respectively. Based on data, it could be concluded that ACA was the most selective to inhibit T47D cell with a selectivity index of 6.6.Keywords: 1’-Acetoxychavicol acetate, galangal (Alpinia galanga), selective index, cytotoxic
T47D cells arrested at G2M and Hyperploidy Formation Induced by a Curcumin’s Analogue PGV-1 Muhammad Da’i; Umar Anggara Jenie; Supardjan AM; Masashi Kawaichi; Edy Meiyanto
Indonesian Journal of Biotechnology Vol 12, No 2 (2007)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (305.077 KB) | DOI: 10.22146/ijbiotech.7776

Abstract

its chemical structure than curcumin. As a curcumin analogue, PGV-1 was considered to have anticanceractivities. This research was conducted to study the effect of PGV-1 on the cycle progression of T47D cells. Cytotoxiceffects of PGV-1 on T47D cells were determined using MTT assay, and the the effect on cell cycle progressionwas carried out using flowcytometry. Western blot analysis was used to analyze protein expression correspondingto cell cycle progression. The result showed that at the concentration of 2.5 μM PGV-1 inhibited cell cycleprogression through G2/M arrest and induced of cells hyperploidy formation. The hyperploidy formation inducedby PGV-1 was related to the increase of cdc-2 expression. PGV-1 2.5 μM elevated the level of p21 CIP/KIPthrough p53- independent manner. Apoptosis was also induced by PGV-1 at early phase of treatment indicated byPARP cleavage due to activation of caspase-3/7 after 12 h treatment. The results above suggest that PGV-1 inhibitsthe growth of T47D cells targeted on microtubules.Keywords: PGV-1, G2/M arrest, apoptosis, p21
Acetoxy Chavicol Acetate (ACA) Concentration and Cytotoxic Activity of Alpinia galanga Extract on HeLa, MCF7 and T47D Cancer Cell Lines Andi Suhendi; Erindyah Retno Wikantyasning; Gunawan Setyadi; Arifah Sri Wahyuni; Muhammad Da'i
Indonesian Journal of Cancer Chemoprevention Vol 8, No 2 (2017)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev8iss2pp81-84

Abstract

Due to severe side effect and non-specific chemotherapeutic agent, screening and discovery for cancer therapy are still working, especially from natural resources. Traditionally, people used herbal medicine either to prevent or cure diseases. One of herbal that commonly used in Indonesia is Alpinia galangal. Previous study stated that active compound is acetoxy chavicol acetate (ACA) and active as anticancer. This research aimed to determine ACA concentration and cytotoxic activity of Alpinia galanga extract (AGE) from three local markets on HeLa, MCF7 and T47D cell lines. The galangal used from three local markets namely Pasar Legi Surakarta, Beringharjo Yogyakarta, and Wonogiri. The extraction was performed by maceration using 96% ethanol as solvent. ACA quantitation using UV spectrophotometer at λ = 208.5 nm. Samples were prepared by liquid-liquid extraction using an ethyl acetate. Cytotoxic activities were performed by MTT assay. The result showed that the concentration of ACA of AGE from the three local markets were 3.798; 0.035; and 0.009 % w/w, respectively. Cytotoxic activity, describes as IC50 value, on HeLa cell line of AGE from three local markets, in order were 13.26; 36.32 and > 100 µg/ mL. Meanwhile, AGE from Pasar Legi on MCF7 and T47D cell lines have IC50 value of 15.80; 12.50 µg/ mL, respectively. In contrast, two other samples have IC50 values of greater than 100 µg/ mL. The highest activity was from the highest concentration of ACA on the samples.Key words: Alpinia galanga, HeLa, T47D, MCF7 and Acetoxy chavicol acetate