. Mustofa
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Mechanism of cytotoxic activity of chalcone derivatives against K562 leukemia cell lines Novilla, Arina; Mustofa, .; Astuti, Indwiani; Jumina, .; Suwito, Hery
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 49, No 4 (2017)
Publisher : Journal of the Medical Sciences (Berkala ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.19106/JMedSci004904201701

Abstract

Two chalcone derivatives i.e. (E)-1-(4-aminophenyl)-3-(2,3dimethoxyphenyl)-prop-2-en-1-one (Compound-1), and (E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one) (Compound-2),has been proven to have potential cytotoxic activity. The aim of this study was toevaluate the effect of these compounds on PI3K/Akt signalling pathway in K562 celllines. After incubation with the tested compounds, AKT, caspase-3, STAT3 and cyclinD1 concentrations were measured using ELISA. Furthermore, cell cycle was analysedusing flowcytometry. Imatinib and isotretinoin were used as positive control, whereascell culture without treatment was used as negative control. The AKT concentration aftertreatment with Compound-1 and -2 was significantly lower than that control, imatiniband isotretinoin (p<0.05). The apoptotic indices after treatment with Compound-1 and-2 were significantly higher than control, however they were lower than imatinib andisotretinoin (p<0.05). The caspase-3 concentration after treatment with Compound-1 at5 and 10 μg/mL and Compound-2 at 10 μg/mL was significantly higher than that controland imatinib, however it was lower than isotretinoin (p<0.05). The STAT3 concentrationafter treatment with Compound-1 and -2 was significantly lower than that control andisotretinoin at 50 μg/mL (p<0.05) and similar with imatinib (p>0.05). The cyclin D1concentration after treatment with Compound-1 and -2 was significantly lower than thatcontrol, imatinib and isotretinoin (p<0.05). In addition, Compound-1 and -2 arrested G0/G1 and G2/M phase in K562 cell lines, with comparable results to imatinib and isotretinoin.In conclusion, the mechanism of cytotoxic activity of Compound-1 and -2 are through thePI3K/Akt signalling pathway inhibition, apoptosis induction by upregulation of apoptoticmarkers, and inhibition of cell cycle progression by regulating cell cycle-related factors.
Ondansetron serum concentration and polymorphisms of CYP2D6, ABCB1 and 5-HT3B receptor genes in the treatment of chemoterapy induced nausea and vomiting Perwitasari, DA; Mustofa, .
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 1 (2016)
Publisher : Journal of the Medical Sciences (Berkala ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (407.146 KB) | DOI: 10.19106/JMedSci004801201603

Abstract

This study was aimed to understand differences of ondansetron serum concentrationin each antiemetic responses, polymorphisms of 5HT3B receptor, CYP2D6 and ABCB1genes in Indonesian cancer patients treated with high emetogenic cytostatics. We recruitedcancer patients in Dr Sardjito Hospital treated with cisplatin (≥ 50 mg/m 2) as monotherapyor combination therapy. Patients were treated with ondansetron 8 mg intravenously anddexamethasone 8 mg intravenously and metoclopramide (10 mg orally) after cytostaticadministration until 5 days after chemotherapy. We cathegorized the nausea and vomitinggrade according to the National Cancer Institute Common Toxicity Criteria v.3. We alsodetermined some SNPs of ABCB1, 5HT3B and CYP2D6 genes using realtime PCR. Werecruited 191 cancer patients in this study with the average of ondansetron serumconcentration reached 33.48 ng/ml (SD: 18.54). According to the patients’ response tothe antiemetic, during the acute phase, 21.8% patients experienced acute nausea and30.2% patients experienced acute vomiting. Only the haplotype of CTG-CTG of ABCB1which have significant association with ondansetron serum concentration. EM patients ofCYP2D6 and patients with haplotype of delAG of 5HT3B had lower ondansetron serumconcentration. However, IM patients of CYP2D6 showed higher ondansetron serumconcentration and lower grade of nausea and vomiting. Variations of ABCB1, CYP2D6and 5HT3B may be used as pharmacogenetic marker in predicting antiemetic response incancer patients receiving highly emetogenic cytostatic.
Expression of receptor advanced glycosilation end product (RAGE) and active caspase-3 of the streptozotocin-induced chronic diabetes mellitus Sprague Dawley rats’ sperm with soybean (Glycin max) powder suspension treatment Mustofa, .; Rizal, Dicky Moch; Soejono, Sri Kadarsih
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 45, No 01 (2013)
Publisher : Journal of the Medical Sciences (Berkala ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (13374.651 KB) | DOI: 10.19106/JMedScie004501201301

Abstract

Diabetes mellitus (DM) affects all the process of spermatogenesis. Chronic hyperglycemia in DM increases the expression of receptor for advanced glycosilation end products (RAGE) that is responsible for the activation of signal production of reactive oxygen species (ROS) and caspase 3. Active caspase 3 plays an important role in cell apoptosis. Soybean (Glycin max) is reported to have antihyperglycemic and antiadvanced glycosilation end products (antiAGE) and antioxidants activities. The aim of this study was to evaluate the effect of soybean powder suspension on the expression of RAGE and active caspase 3 of diabetic rats’ sperm. This was an experimental study with post test only control group design using 30 male Sprague Dawley rats, aged 11-12 weeks old and weighed 200-250g. The rats were divided into five groups with six rats in each group. Group 1 was non diabetic rats and  Group 2 was diabetic rats that were given aquadest. Group 3-5 were diabetic rats that were given a soybean powder suspension at dose of 400; 800 and 1600 mg/kg body weight (BW)/day, respectively. Diabetic rats were made by induction of a single intraperitoneal injection of streptozotocin (STZ) at a dose of 60 mg/kg BW. Soybean powder suspension was ingested for four weeks after 14 days STZ induction. Blood glucose levels were monitored before and three days after STZ induction and four weeks after suspension ingestion. The expression of RAGE and active caspase-3 were analyzed using immunohistochemistry method four weeks after suspension ingestion. The results showed that soybean powder suspension ingestion significantly decreased blood glucose level of diabetic rats toward normality (p<0.05). However, the expression of RAGE and active caspase-3 in diabetic rats’ sperm were not significantly lower than those after suspension ingestion. In conclusion, soybean powder suspension does not significantly affect the expression of RAGE and active caspase-3 in diabetic rats’ sperm.
Synergistic interaction between quercetin and doxorubicin on MCF-7 human breast cancer cell line Purba, Abdul Khairul Rizki; Mustofa, .; Astuti, Indwiani
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 45, No 03 (2013)
Publisher : Journal of the Medical Sciences (Berkala ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (322.697 KB) | DOI: 10.19106/JMedScie004503201303

Abstract

The effectiveness of doxorubicin has decreased due to resistance of cancer cells. One of thenatural ingredients that are proven to reduce the resistance to anticancer is quercetin. Quercetininteracts with doxorubicin via a competition of P-glycoprotein (P-gp) transporter activity. Theaim of this study is to evaluate the interaction of quercetin and doxorubicin as cytotoxicityeffect on MCF-7 cells. Cytotoxicity test was conducted by the MTT method. Mechanism ofinteraction between doxorubicin and quercetin was evaluated with isobologram analysis.Doxorubicin and quercetin inhibited the growth of MCF-7 cells significantly. Doxorubicin andquercetin respectively had IC50 of 21M and 103 M. The interaction of doxorubicin and quercetinwere characterized by the amount of doxorubicin IC50 equivalent and quercetin IC50 equivalentless than 1 and the point-intercept of each IC50 notation equivalent plotted on the graph belowthe additive line. Analysis of isobolograms indicated that the interaction doxorubisn and quercetinin each of the ratios had synergy. Quercetin can be considered to be in a combination wit
Cytotoxicity of α-terpineol in HeLa cell line and its effects to apoptosis and cell cycle Noor, Rasuane; Astuti, Indwiani; Mustofa, .
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 46, No 01 (2014)
Publisher : Journal of the Medical Sciences (Berkala ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (649.907 KB) | DOI: 10.19106/JMedScie004601201401

Abstract

α-Terpineol is a natural compound of terpenoid alcohols class. However, it can be synthesizedfrom α-pinene of turpentin content. α-Terpineol has been reported as potential anticancer agentdue to its activity on inhibition of cells growth and induction of tumor cell death. However, itsanticancer activity in HeLa cervical cancer cells line has never been studied, yet. The aim of thisstudy was to evaluate the cytotoxicity of α-terpineol and its effects to apoptosis and cell cycle.This was a quasi-experimental study with post-test only with non-equivalent control groupdesign. Cytotoxicity of á-terpineol was evaluated using MTT cell viability assay. The effect of α-terpineol on cell apoptotis was tested using acridine orange-ethidium bromide staining method,whereas its effect on cell cycle was evaluated by flowcytometry method. The results showedthat α-terpineol had cytotoxicity against HeLa cell with an IC50 value about 12.46 μg/mL.Furthermore, α-terpineol induced the HeLa with an IC50 value about 13.12 μg/mL. Cell accumulationat G1 phase during cell cycle after incubation with α-terpineol (52.78)was observed. In conclusion,α-terpineol is potential as an anticancer due to its ability to induce cell apoptosis and to inhibitthe cell cycle at G1 phase.
Antimicrobial activity of bioactive compounds isolated from Swietenia mahagoni (L) Jacq. against Staphylococcus aureus and Pseudomonas aeruginosa Darussalam,, Handry; Nuryastuti, Titik; Mursiti, .; Mustofa, .
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 46, No 04 (2014)
Publisher : Journal of the Medical Sciences (Berkala ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (107.331 KB) | DOI: 10.19106/JMedScie004604201402

Abstract

Widespread bacterial resistance has led to more difficult to treat infectious diseases with availableantibiotics. Therefore, new antibiotics are needed face of the growing antibiotic resistance. Swieteniamahagoni (L.) Jacq. is one of potential medicinal plants as a source new antibiotics. Five compoundshave been isolated from an ethanolic extract of S. mahagoni (L.) Jacq., however its antimicrobialactivity has not been investigated, yet. This study was conducted to evaluate the antimicrobialactivity of these compounds. Minimal Inhibitory Concentration (MIC) and Minimal BactericidalConcentration (MBC) were determined against Staphylococcus aureus and Pseudomonas aeruginosastrains. Among five compounds tested, compound 3 (3,4,5,6,7-pentaethyl-1-methoxy-1H-indazole)and compound 4 (5-ethyl-6-methoxymethyl-2-methyl-1,2-dihydropyridine) were found to be activeagainst the bactrial strains tested with the MICs and MBCs values ranged from 50 to 100 μg/mL. Inconclusion, among five compounds isolated from S. mahagoni (L.) Jacq., compound 3 and 4showed moderate antimicrobial activity against S. aureus and P. aeruginosa strains.
Analysis of Enzyme Activity of Alcohol Dehydrogenase and Alcohol Dehydrogenase 3 (ADH3) Gene Polymorphism of Alcoholics and Non-Alcoholics in Indonesia. Suhartini, .; Mustofa, .; Nurhantari, Yudha; Rianto, Bambang Udji Djoko
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 2 (2016)
Publisher : Journal of the Medical Sciences (Berkala ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (766.347 KB) | DOI: 10.19106/JMedSci004802201604

Abstract

ABSTRACTAlcohol is an addictive substance that is often misused worldwide, including in Indonesia. Ninety percent of the alcohol that enters the body will be metabolized in the liver using the alcohol dehydrogenase (ADH) enzyme. It is important to determine the activity of ADH enzyme and ADH3 gene polymorphism on alcoholics and non-alcoholics in Yogyakarta, Indonesia. The aim of the study is to determine ADH activity and identify ADH3 gene polymorphism of alcoholics and non-alcoholics in Yogyakarta, Indonesia. This study was an observational study with a cross-sectional design method. Blood samples were taken from 71 Javanese alcoholics and 71 non-alcoholics of Javanese descent in Yogyakarta, Indonesia. The participants were initially requested to sign an informed consent form. Examination of ADH enzyme activity used the spectrophotometry method and ADH3 gene polymorphism was assessed with PCR-RFLP using Ssp I restriction enzyme. The activity of ADH enzyme in all individuals appeared to be a slower type. The average of the ethanol value of alcoholics and non-alcoholics were 0.05554 mM and 0.0758 mM respectively. Gene type of alcoholics were ADH3*2(75.4%), ADH3*1/3*2(21.5%), and ADH3*1(3.1%), and non-alcoholics were ADH3*2(88.6%), ADH3*1/3*2(10.0%), and ADH3*1(1.4%). There were no significant differences between the activity of ADH with polymorphism of ADH3 gene in either alcoholics and non-alcoholics (p>0,05). Conclusion: The activity of ADH enzyme in all participants appeared to be a slower type. Most of the ADH3 gene polymorphism of alcoholics and non-alcoholics were both ADH3*2 (75.4% and 88.6%). There was no differences of ADH enzyme activity with ADH3 gene polymorphism between alcoholics and non-alcoholics of Javanese population in Yogyakarta, Indonesia.
The SLCO1B1*15 haplotype associated with lower clinical outcome in Indonesian tuberculosis patients Ang, Sunarto; Nugroho, Akhmad Kharis; Sadewa, Ahmad Hamim; Hakim, Lukman; Mustofa, .
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 50, No 1 (2018)
Publisher : Journal of the Medical Sciences (Berkala ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (351.494 KB) | DOI: 10.19106/JMedSci005001201806

Abstract

Rifampin is one of first-line drugs for the treatment of tuberculosis. In Indonesia nearly alltuberculosis patients show lower rifampin plasma concentrations possibly due to genetics.Rifampin is a substrate of the organic anion-transporting polypeptide 1B1 (OATP 1B1)encoded by the solute carrier organic anion transporter family member 1B1 (SLCO1B1).This study aimed to identify haplotype polymorphisms of tuberculosis drug transporterswith an impact on clinical outcome in tuberculosis patients. Thirty-six patients from AbdulWahab Sjahranie General Hospital, Samarinda, East Kalimantan were involved in thestudy. Buffy coat from patient blood samples were tested for SLCO1B1 and SLCO1B3polymorphisms by RFLP and ARMS PCR, whereas the clinical outcome was examinedbased on the sputum conversion. The frequency of patients with SLCO1B1*15 haplotypewas 63.9%. The SLCO1B1*15 haplotype was associated with susceptibility to failureof clinical outcome (p=0.005; RR=4.52; 95% CI: 1.22-16.64). The OATP1B1*15haplotype revealed that the failure of clinical outcome was markedly increased comparedto the three other haplotypes. These results suggest that the SLCO1B1*15 haplotypeis an important predisposing factor for lower clinical outcome. Our data indicate thatindividualized treatment should be considered for Indonesian tuberculosis patients basedon genetics characteristics of patients.
8-HIDROKSIISOKAPNOLAKTON-2',3'-DIOL, KUMARIN BIOAKTIF DARI Micromelum minutum Susidarti, Ratna Asmah; Rahmani, Mawardi; Sukari, Mohd. Aspollah; Ali, Abdul Manaf; Mustofa, .; Yasmina, Alfi; Handayani, Sri; Mintarsih, Betty; Ikawati, Muthi’; Septisetyani, Endah Puji
JFIOnline | Print ISSN 1412-1107 | e-ISSN 2355-696X Vol 4, No 3 (2009)
Publisher : Indonesian Research Gateway

Show Abstract | Download Original | Original Source | Check in Google Scholar

Abstract

Separation of leaves chloroform extract of Micromelum minutum (Rutaceae) yielded a new coumarin, 8-hydroxyisocapnolactone-2¢,3¢-diol. The structure of this compound was characterized by UV, IR, MS and NMR spectroscopic methods, including 1H, 13C, HSQC, COSY, HMBC dan NOESY experiments. This compound is significantly toksisk towards several cancer cell lines (CEM-SS, HL60, HeLa, HepG2, MCF7, T47D and NS1), active against chloroquin sensitive (D10) and resistance (FCR3) Plasmodium falciparum and showed strong antibacterial activity against Bacillus Subtilis mutan, Bacillus. Subtilis wild type, Pseudomonas Aeruginosa dan Staphylococcus aureus resisten meticilin).  ABSTRAK Pemisahan ekstrak kloroform daun Micromelum minutum (Rutaceae) menghasilkan suatu kumarin baru, 8-hidroksiisokapnolakton-2΄,3΄-diol yang strukturnya diidentifikasi secara spektroskopi UV, IR, MS dan NMR termasuk 1H, 13C, HSQC, COSY, HMBC dan NOESY. Senyawa tersebut secara signifikan toksik terhadap beberapa sel kanker (CEM-SS, HL60, HeLa, HepG2, MCF7, T47D dan NS1), aktif terhadap Plasmodium falciparum yang sensitif (D10) maupun resisten (FCR3) kloroquin dan mempunyai aktivitas antibakteri yang kuat terhadap Bacillus Subtilis mutan, Bacillus. Subtilis wild type, Pseudomonas Aeruginosa dan Staphylococcus aureus resisten meticilin).
Effects of resistant starch of mixed tubers snacks on glucose metabolism, leptin, visceral fat and body mass index in type 2 diabetes mellitus (T2DM) Hidayat, Jenny; Sunarti, .; Mustofa, .; Sadewa, Ahmad Hamim
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 51, No 1 (2019)
Publisher : Journal of the Medical Sciences (Berkala ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (259.686 KB) | DOI: 10.19106/JMedSci005101201906

Abstract

Resistant starch could lower blood glucose, decrease adipocyte in adipose tissue and affect satiety hormones such as leptin. Tubers and pumpkin have high content of resistant starch, but their effectiveness to type 2 diabetes mellitus (T2DM) has not been known clearly. This research was conducted to determine the effectiveness of snack consumption made from tubers and pumpkins to BMI, visceral fat, glucose and leptin levels in the blood of T2DM patients and the correlation between the variables. The research method was pre-post clinical trial. Sixteen T2DM patients were in treatment (RS) and control groups. Subjects in RS group were given snack twice daily for 4 weeks. After following wash out process for 4 weeks, the same subjects was continued as subjects’ control. Paired t-test and/or Wilcoxon-test was used to analyze the differences between values before and after treatment in the group and between groups. Pearson test was used to analyze the correlation of BMI, visceral fat, glucose and leptin level. The visceral fat was increased in RS group (p=0.04) after 4 weeks consuming snack but decrease in control group (p=0.04) without significant change of BMI. Leptin level was decreased (p=0.00) in RS group. Blood glucose significantly decreased (p=0.01) and leptin level increased slightly in control group. Comparing the RS and control group at the end of study, there were significantly different in the variation of visceral fat in the female groups (p=0.05) and leptin (p=0.05). Visceral fat correlated with BMI in the RS and control group. In conclusion, the mixed tubers and pumpkin snack decreased the leptin level but increased visceral fat.