Indonesian Journal of Cancer Chemoprevention
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in vitro Antidiabetic, Antioxidant and Cytotoxic Activities of Syzygium cumini Fractions from Leaves Ethanol Extract
Full text linkEthanol extract of Syzygium cumini (jamblang) leaves reveal its significant α-glucosidase inhibitory activity which perform the potential activity of this plant extract as antidiabetic agent. However, other bioactivities of this plant extract have been reported. The aim of current study was to evaluate the comparison of in vitro antidiabetic, antioxidant and cytotoxic activity of S. cumini fractions. The S. cumini leaves ethanol extract was fractionated by using column chromatography with n-hexane, ethyl acetate and methanol as eluents. Seven fractions were obtained from column chromatography (F1-7). The results showed that the best antidiabetic activity was found in F5 (93% α-glucosidase inhibitory activity), the best antioxidant activity was found in F4 (83% inhibition of DPPH free radical) and the best cytotoxic activity was found in F2 (69% growth inhibition of T47D breast cancer cell line). Therefore besides in vitro antidiabetic activity, fractions of S. cumini leaves ethanol extract also showed antioxidant and cytotoxic activities. Since the results showed that the most active fractions for antidiabetic, antioxidant and cytotoxicity were differed, it could be possible to isolate the different potential active compounds for each activity.Keywords : Syzygium cumini, α-glucosidase inhibitor, DPPH, cytotoxicit
A New Compound (8,9) -Furanyl-Pterocarpan-3-Ol Used for Standardization of Bengkuang (Pachyrhizus erosus) Extract as Sunscreen and Skin Whitening Agent
Full text linkBengkuang (Pachyrhizus erosus) has been traditionally used as sun screening and skin whitening. The active compounds in bengkuang extract already published included their activities in antioxidant and skin whitening. However, standardization of bengkuang extract has not been studied. This research aims to find out the analysis procedure by High Performance Liquid Chromatography to make standardization bengkuang extract.The first step of this research was collecting bengkuang from Prembun, Central Java, Indonesia in dry season. After cleaning and peeling, bengkuang root was sliced, dried and ground to make powder. Then followed by extraction using Soxhlet in petroleum ether and subsequently in methanol. Methanol extract was evaporated and then partitioned with ethyl acetate-water. Ethyl acetate fraction was evaporated and then separated in open column chromatography using silica gel as stationary phase and a gradient mixture of chloroform-ethyl acetate-methanol as mobile phase. Bio guided fraction method was used for separation and purification to get isolated compounds. The isolated compounds obtained from this fractionation were then elucidated and analyzed their activities.A new compound (8,9-furanyl-pterocarpan-ol) has been selected as a biomarker for extract standardization. The optimum of HPLC condition for standardization consisted of a column (Zorbax SB-C18; i.d. 0.46 cm; 5 μm particle size), mobile phase (gradient elution of MeOH-water) with flow rate of 1 ml/min and detector (UV-detector at 293 nm). The obtained LOD value was 0.51 ± 0.02 µg. The potentials of this compound to absorb UV ray, antioxidant and anti-tyrosinase were 4.018 mAU*S/mml; 2.113±0.001mM (SC50); 7.19±0.11 mM (IC50), respectively.Keywords : bengkuang (Pachyrhizus erosus) extract, (8,9)-furanyl-pterocarpan-3-ol, standardization, sunscreen, skin whitenin
Expression of Human Erythropoietin Containing 2 Additional N-Link in CHO-K1 Cells under Different Culture Conditions
Full text linkHuman erythropoietin (hEPO) is a glycoprotein that regulates the formation of erythrocytes and mainly used in anemia patients. Previously, we have reported the expression of modified human EPO with 2 additional N-linked in mammalian cell CHO-K1. The aim of this current research was to study the optimum condition for modified recombinant hEPO (rhEPO) production in CHO-K1. To do this, several parameters of culture conditions were applied including antibiotic concentrations, seeding densities, time of incubations, fetal bovine serum (FBS) concentrations and cell culture media. The result showed that the presence of antibiotic G418 improved the expression level with the highest was at 1% of concentration. Meanwhile, seeding density of 2–3x105 cells/6 cm dish and seven day of incubation time were the best condition for rhEPO protein expression. From five different combination media used, F12 medium with 10% FBS gave the highest expression of rhEPO protein. From this study was also found that at passage 16 the expression level was still increasing proving that the clone expressing the protein of our interest is promisingly stable.Keywords : EPO, erythropoietin, protein expression, CHO-K1, optimatio
Revelation of New Compound from Ethanolic Extract of Fragaria x ananassa var. Lembang
Full text linkFragaria x ananassa (strawberry) is a subtropical plant that can adapt well in tropical highlands. Fragaria x ananassa have been widely used to cope with health problems. The active compound component of secondary metabolites contained in Fragaria x ananassa has the potential as an antioxidant. This research is done to isolate secondary metabolites from extract of Fragaria x ananassa fruits. Extract Fragaria x ananassa was produced by maceration using ethanol as the solvent. Separation and isolation compound were carried out using Vacuum Liquid Chromatography (VLC) and Gravity Column Chromatography (GCC) guided by Thin Layer Chromatography (TLC) using hexane: ethyl acetate (3:7) as the eluent. The flavonoid compound was determined by the total content of phenolic and flavonoid in extract of Fragaria x ananassa fruits. The results of total phenolic content and total flavonoid content were 0.1130 mg/g and 0.0112 mg/g, respectively. The alkaloid compound was determined by Dragendorff testing. The elucidation of the structure by Fourier Tansform Infrared (FTIR), Nuclear Magnetic Resonance (NMR), and Liquid Chromatography Mass Spectrometry (LCMS) showed that the active compound contained in the secondary metabolite of extract ethanol from Fragaria x ananassa is 3-Cyclopentyl-5-(1-hydroxyethyl)-1,6-dihydro-7H-pyrazolo[4,3- d]pyrimidin-7-one.Keywords: Fragaria x ananassa extract, flavonoid, alkaloid, total phenolic and flavonoid content, FTIR, NMR, LCMS
Growth Inhibitory Property of Pentagamavunone-0 (PGV-0) on 4T1 Cells under Stress Condition : 2D and 3D Culture Model
Full text linkPentagamavunone-0 (PGV-0), one of the curcumin analogue, is reported to have a cytotoxic effect on various cancer cells. This study aimed to explore the growth inhibitory effects of PGV-0 against highly-metastatic breast cancer, 4T1 cells under stress condition covering 2D and 3D speroid cytotoxic, anti-migration, and suppression of MMP-9. PGV-0 showed cytotoxic effects on 2D and 3D 4T1 cells with IC50value of 49 μM and 26 μM, respectively. In addition, PGV-0 performed anti-migratory effect. The single treatment at 25 μM PGV-0 and 50 μM showed inhibitory effect on cell migration by 54% and 51% respectively. whilst, the combination of PGV-0 at the concentration of 25 μM and 50 μM with doxorubicin significantly inhibited cell migration by 41% and 38%, respectively. The gelatin zymography assay showed that PGV-0 decreased MMP-9 expression both in a single treatment and in combination with doxorubicin. In conclusion, PGV-0 is potential to be developed as anti-tumorigenesis agent on highly-metastatic breast cancers.Keywords: Pentagamavunone-0 (PGV-0), anti-migration, MMP-9, 4T1 cells, spheroi
The Optimization Method for Synthesis of 99mTc-Rutin as Potential Radiotracer in The Development of Cancer Drugs From Flavonoid
Full text linkBased on the Basic Health Research Data of Ministry of Health's of Indonesia in 2013, mortality rates from malignant and tumor malignancies in Indonesia are still high with prevalence of cancer is about 1.4%. Chemotherapy is still the primary choice in cancer modality that uses chemotherapeutic drugs to eradicate and inhibit the growth of cancer cells; however the cost this treatment is extremely high. Therefore, patient tends to seek alternative treatment such as consuming traditional herbal medicine for cancer treatment. Rutin is one of the attractive phytochemicals flavonoids because of its antioxidant activities. However, as traditional herbal medicine, its effectiveness is not yet been fully established due to the lack of scientific information. A radiotracer can be defined as a specific radiolabeled molecule that monitors the in vivo behaviour of a functional molecule, and can be used to provide biological information in a living system. Hence, to provide pharmacological information of rutin for cancer treatment, we synthesized radiolabeled flavonoid 99mTc-rutin as radiotracer. The aim of the present study is to develop 99mTc-rutin under varying conditions of rutin quantity, reducing agent concentration and incubation time. Labeling studies were performed by changing the selected parameters one by one and optimum labeling conditions were determined. After observing the conditions for maximum labeling efficiency, 99mTc-rutin was obtained with preparation of 700 μg of rutin with addition of 20 μg of SnCl2.2H2O as reductor and 1-3 mCi 99mTcO4- without any incubation. Radiochemical yield of 99mTc-rutin was determined with radio thin layer chromatography which was found 99.28 ± 0.14% and stable up to 4 hour. From the result of this study, the successfully labeled 99mTc-rutin can be used as a reference for following preclinical study. Furthermore radiolabeled 99mTc-rutin is expected as tools in research and development of rutin as cancer drugs from natural product to obtain detailed information its efficacy.Keywords: radiotracer, 99mTc-rutin, cancer, labeled compound
The Effect of Red Pitaya Peel (Hylocereus polyrhizus Extract) on Malondialdehida Levels and Histopathology Profile in Diazinon Induced Rat (Rattus norvegicus)
Full text linkDiazinon, an organophosphate insecticide is widely used in agricultural sectors. The metabolic products of this organophosphate compound can increase Reactive Oxygen Species (ROS) in the body. It causes complications to the various organs, one of which is gastric. Red pitaya peel extract (Hylocereus polyrhizus) has high antioxidant activity in lowering ROS, in cases of diazinon poisoning. This study aims to determine the effectiveness of redpitaya peel extract in reducing the levels of Malondialdehyde (MDA) and repairing histopathological damage of rats induced by diazinon. This study used 20 tails of male white Wistar rats (Rattus norvegicus) from 8-12 weeks of age with the average weight of 150 grams . The subject was divided into 5 groups, which were negative control (-), positive control (+), treatment 1 (P1), treatment 2 (P2), and treatment 3 (P3). A dose of 40 mg/kg BW of Diazinon was given orally every day through feeding tube (sonde) for 5 consecutive days. Red pitaya peel extract was given to test groups with a dose of 150 mg/150 g BW, 200 mg/150 g BW and 250 mg/150 g BW, for 14 days. MDA levels were measured using the Thiobarbituric acid (TBA) test. Gastric histopathology features were stained with Hematoxylin-Eosin (HE) after 14 days. The MDA levels were analyzed quantitatively by ANOVA using SPSS version 22 for Windows and continued with honestly significant difference (HSD) test (α = 5%) and gastric histopathology were analyzed descriptively. The results showed that the extract of red pitaya peel with dose of 150 mg/150 g BW significantly (p<0.01) reduces MDA level in gastric dan improves the histopathology of the gastric. Red pitaya peel extract at a dose of 150 mg/150 g BW was able to significantly decrease MDA levels and improve the histopathology feature of the gastric in white rats induced by diazinon. So this can be summarised that giving red pitaya extract in rats have a very significant effect on the level of malondialdehyde production and it could repair rats stomach tissue that induced by diazinon.Keywords: diazinon, histopathology, MDA, red pitaya pee
Treatment of Neuroendocrine Tumors (NETs) Using Somatostatin Analogs: Current View, Clinical Achievements and Future Perspectives
Full text linkNeuroendocrine tumors (NETs), previously known as carcinoid tumors, are a heterogeneous group of neoplasms which originate from cells of the endocrine or nervous system with an overall incidence of 1–5 cases per 100,000 individuals per year. Recent studies showed that their incidence has dramatically increased worldwide over the last few years. The majority of NETs overexpress the somatostatin receptors (SSTRs) in tumor cells which are further being used as the important targets for therapy purposes using somatostatin analogs (SSAs) such as octreotide and lanreotide. Like native somatostatin, SSAs bind to SSTRs and induce a range of cellular effects, including antitumor activity. Antitumor activity of SSAs and their high binding properties for the SSTRs have become valuable tools for developing advanced treatment of NETs. Consequently, SSAs have been used widely in routine clinical practice, especially for treatment of various types of NETs. Despite treatment using SSAs have made a positive contribution, recent development suggests that the used of SSAs in combination with chemotherapy or peptide receptor radionuclide therapy (PRRT) can improve clinical outcome in patients with NETs. This review provides an overview of recent trend in the treatment of NETs using SSAs, their clinical achievements in the last few years and their potential applications in the future.Keywords: neuroendocrine tumors, treatment, somatostatin analogs, chemotherapy, PRRTNeuroendocrine tumors (NETs), previously known as carcinoid tumors, are a heterogeneous group of neoplasms which originate from cells of the endocrine or nervous system with an overall incidence of 1–5 cases per 100,000 individuals per year. Recent studies showed that their incidence has dramatically increased worldwide over the last few years. The majority of NETs overexpress the somatostatin receptors (SSTRs) in tumor cells which are further being used as the important targets for therapy purposes using somatostatin analogs (SSAs) such as octreotide and lanreotide. Like native somatostatin, SSAs bind to SSTRs and induce a range of cellular effects, including antitumor activity. Antitumor activity of SSAs and their high binding properties for the SSTRs have become valuable tools for developing advanced treatment of NETs. Consequently, SSAs have been used widely in routine clinical practice, especially for treatment of various types of NETs. Despite treatment using SSAs have made a positive contribution, recent development suggests that the used of SSAs in combination with chemotherapy or peptide receptor radionuclide therapy (PRRT) can improve clinical outcome in patients with NETs. This review provides an overview of recent trend in the treatment of NETs using SSAs, their clinical achievements in the last few years and their potential applications in the future.Keywords: neuroendocrine tumors, treatment, somatostatin analogs, chemotherapy, PRR
A Brief Outlook on Pharmacogenetics (PGx): Focus in MicroRNAs (miRNAs) and Cancer Stem Cells (CSCs)
Full text linkIt has been known that there are differences in response to medications both in terms of clinical activity and side effects. Among all influencing factors, genetic variation has been considered to play a crucial part. By genetic investigation, the differences in drug metabolism, transport and target could be disclosed. Termed as “pharmacogenetics (PGx)”, that focuses on the variants within one or more candidate genes. Genetic tests have been started for screening polymorphisms prior to drug prescription, moreover many biomarkers were developed in oncology. Recent PGx investigations have been conducted to identify mRNAs, microRNAs (miRNAs) and other downstream signals that are affected by variation in genes that might cause drug response variability. Another intriguing study related to PGx in cancer stem cells (CSCs) has recently aroused. CSC shows more resistant behavior to drug. CSCs are subpopulation of cells, which share some same markers with stem cells. CSC can induce specific signal transduction pathways. Variation in genes affect CSCs activity are generally neglected in the past PGx studies. This could be one of the explanation why past PGx studies in cancer cell do not achieve optimal clinical outcome. Keywords : pharmacogenetics, pharmacogenomics, microRNAs, cancer stem cell
Caesalpinia sappan L. Ethanolic Extract Decrease Intracellular ROS Level and Senescence of 4T1 Breast Cancer Cells
Full text linkHighly and uncontrolled cell proliferation on cancer cells may boost ROS level intracellular accumulation up significantly. Sappan heartwood (Caesalpinia sappan L.) have been known to have cytotoxicity effect toward several cancer cells. This research was conducted to develop Caesalpinia sappan L. heartwood ethanolic extract (CSE) as chemopreventive agent which can be used as cancer therapy, looked from antioxidant and anti-senescence activity toward 4T1 breast cancer cell. CSE was obtained through maceration using ethanol 70% as solvent. Cytotoxicity activity of CSE was done by using MTT assay with IC50 as parameter. This IC50 was used as basic to the next assay, ROS assay by using DCFDA staining flowcytometry to look ROS level intracellular of CSE toward 4T1 cell and senescence assay by using senescence associated β-galactosidase (SA β-gal) assay with % cell senescence as their parameter. CSE toxic to 4T1 cell that proved from IC50 value of 25 µg/mL. Single treatment of CSE on concentration 12,5; 25; and 37.5 µg/mL able to suppress ROS level intracellular. If compared with untreated cell, single treatment of CSE on concentration 6 and 12 µg/mL showed % cell senescence not significantly different. Based on this result, CSE is cytotoxic, has antioxidant and antisenescence activity, so it has great potential to developed as chemoprevention agent on cancer therapy.Keywords : Caesalpinia sappan L., 4T1 breast cancer line, Reactive Oxygen Species (ROS), anti-senescenc