Displaying publications 21 - 40 of 143 in total

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  1. Fulltext The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells
    Etti IC, Abdullah R, Kadir A, Hashim NM, Yeap SK, Imam MU, et al.
    PLoS One, 2017;12(8):e0182357.
    PMID: 28771532 DOI: 10.1371/journal.pone.0182357
    Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.
  2. Respiratory carriage of hypervirulent Klebsiella pneumoniae by indigenous populations of Malaysia
    Das S, Pandey AK, Morris DE, Anderson R, Lim V, Wie CC, et al.
    BMC Genomics, 2024 Apr 17;25(1):381.
    PMID: 38632538 DOI: 10.1186/s12864-024-10276-4
    Klebsiella pneumoniae is a Gram-negative Enterobacteriaceae that is classified by the World Health Organisation (WHO) as a Priority One ESKAPE pathogen. South and Southeast Asian countries are regions where both healthcare associated infections (HAI) and community acquired infections (CAI) due to extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant K. pneumoniae (CRKp) are of concern. As K. pneumoniae can also exist as a harmless commensal, the spread of resistance genotypes requires epidemiological vigilance. However there has been no significant study of carriage isolates from healthy individuals, particularly in Southeast Asia, and specially Malaysia. Here we describe the genomic analysis of respiratory isolates of K. pneumoniae obtained from Orang Ulu and Orang Asli communities in Malaysian Borneo and Peninsular Malaysia respectively. The majority of isolates were K. pneumoniae species complex (KpSC) 1 K. pneumoniae (n = 53, 89.8%). Four Klebsiella variicola subsp. variicola (KpSC3) and two Klebsiella quasipneumoniae subsp. similipneumoniae (KpSC4) were also found. It was discovered that 30.2% (n = 16) of the KpSC1 isolates were ST23, 11.3% (n = 6) were of ST65, 7.5% (n = 4) were ST13, and 13.2% (n = 7) were ST86. Only eight of the KpSC1 isolates encoded ESBL, but importantly not carbapenemase. Thirteen of the KpSC1 isolates carried yersiniabactin, colibactin and aerobactin, all of which harboured the rmpADC locus and are therefore characterised as hypervirulent. Co-carriage of multiple strains was minimal. In conclusion, most isolates were KpSC1, ST23, one of the most common sequence types and previously found in cases of K. pneumoniae infection. A proportion were hypervirulent (hvKp) however antibiotic resistance was low.
  3. Fulltext Induction of cell cycle arrest and apoptosis in caspase-3 deficient MCF-7 cells by Dillenia suffruticosa root extract via multiple signalling pathways
    Foo JB, Yazan LS, Tor YS, Armania N, Ismail N, Imam MU, et al.
    BMC Complement Altern Med, 2014;14:197.
    PMID: 24947113 DOI: 10.1186/1472-6882-14-197
    Dillenia suffruticosa root dichloromethane extract (DCM-DS) has been reported to exhibit strong cytotoxicity towards breast cancer cells. The present study was designed to investigate the cell cycle profile, mode of cell death and signalling pathways of DCM-DS-treated human caspase-3 deficient MCF-7 breast cancer cells.
  4. β Mangostin suppress LPS-induced inflammatory response in RAW 264.7 macrophages in vitro and carrageenan-induced peritonitis in vivo
    Syam S, Bustamam A, Abdullah R, Sukari MA, Hashim NM, Mohan S, et al.
    J Ethnopharmacol, 2014 Apr 28;153(2):435-45.
    PMID: 24607509 DOI: 10.1016/j.jep.2014.02.051
    The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana.
  5. Fulltext Induction of apoptosis through oxidative stress-related pathways in MCF-7, human breast cancer cells, by ethyl acetate extract of Dillenia suffruticosa
    Tor YS, Yazan LS, Foo JB, Armania N, Cheah YK, Abdullah R, et al.
    BMC Complement Altern Med, 2014;14:55.
    PMID: 24524627 DOI: 10.1186/1472-6882-14-55
    Breast cancer is one of the most dreading types of cancer among women. Herbal medicine has becoming a potential source of treatment for breast cancer. Herbal plant Dillenia suffruticosa (Griff) Martelli under the family Dilleniaceae has been traditionally used to treat cancerous growth. In this study, the anticancer effect of ethyl acetate extract of D. suffruticosa (EADs) was examined on human breast adenocarcinoma cell line MCF-7 and the molecular pathway involved was elucidated.
  6. Typhonium flagelliforme induces apoptosis in CEMss cells via activation of caspase-9, PARP cleavage and cytochrome c release: its activation coupled with G0/G1 phase cell cycle arrest
    Mohan S, Abdul AB, Abdelwahab SI, Al-Zubairi AS, Sukari MA, Abdullah R, et al.
    J Ethnopharmacol, 2010 Oct 5;131(3):592-600.
    PMID: 20673794 DOI: 10.1016/j.jep.2010.07.043
    The plant Typhonium flagelliforme (TF), commonly known as 'rodent tuber' in Malaysia, is often used as traditional remedy for cancer, including leukemia.
  7. Typhonium flagelliforme inhibits the proliferation of murine leukemia WEHI-3 cells in vitro and induces apoptosis in vivo
    Mohan S, Abdul AB, Abdelwahab SI, Al-Zubairi AS, Aspollah Sukari M, Abdullah R, et al.
    Leuk. Res., 2010 Nov;34(11):1483-92.
    PMID: 20569984 DOI: 10.1016/j.leukres.2010.04.023
    Typhonium flagelliforme (TF) is a tropical plant, traditionally used by the ethnic population of Malaysia for the cure of various cancers. This plant had shown to induce antiproliferative effect as well as apoptosis in cancer cells. However, there is no available information to address that TF affects murine leukemia cells in vitro and in vivo. Here, we investigated in vitro and in vivo effects of TF on murine leukemia WEHI-3 cells. It was found that the growth of leukemia cells in vitro was inhibited by the various extracts of TF. Among these fractions, the dichloromethane (DCM) tuber extracts of TF showed the lowest IC(50) (24.0 ± 5.2 μg/ml) and had demonstrated apoptogenic effect when observed under fluorescent microscope. We investigated the in vivo effects of DCM tuber extracts of TF on murine leukemia cells, and the results showed that the counts of immature granulocytes and monocytes were significantly decreased in peripheral blood of BALB/c leukemia mice after the oral administration of DCM tuber extracts of TF for 28 days with three doses (200, 400 and 800 mg/kg). These results were confirmed by observing the spleen histopathology and morphology of enlarged spleen and liver in leukemia mice when compared with the control. Furthermore, the cell death mechanism in the spleen tissue of treated mice was found via apoptosis.
  8. Effect of recombinant human erythropoietin and doxorubicin in combination on the proliferation of MCF-7 and MDA-MB231 breast cancer cells
    Radwan EM, Abdullah R, Al-Qubaisi MS, El Zowalaty ME, Naadja SE, Alitheen NB, et al.
    Mol Med Rep, 2016 May;13(5):3945-52.
    PMID: 26987078 DOI: 10.3892/mmr.2016.4989
    Patients with cancer often exhibit signs of anemia as the result of the disease. Thus, cancer chemotherapies often include erythropoietin (EPO) in the regime to improve the survival rate of these patients. The aim of the present study was to determine the effect of EPO on doxorubicin-treated breast cancer cells. The cytotoxicity of doxorubicin alone or in combination with EPO against the MCF-7 and MDA-MB‑231 human breast cancer cells were determined using an MTT cell viability assay, neutral red (NR) uptake assay and lactate dehydrogenase (LDH) assay. The estimated half maximal inhibitory concentration values for doxorubicin and the combination of doxorubicin with EPO were between 0.140 and 0.260 µg/ml for all cells treated for 72 h. Treatment with doxorubicin in combination with EPO led to no notable difference in cytotoxicity, compared with treatment with doxorubicin alone. The antiproliferative effect of doxorubicin at a concentration of 1 µg/ml on the MDA‑MB‑231 cells was demonstrated by the decrease in viable cells from 3.6x10(5) at 24 h to 2.1x10(5) at 72 h of treatment. In order to confirm apoptosis in the doxorubicin-treated cells, the activities of caspases-3/7 and ‑9 were determined using a TBE assay. The results indicated that the activities of caspases-3/7 and ‑9 were significantly elevated in the doxorubicin-treated MDA-MB-231 cells by 571 and 645%, respectively, and in the MCF 7 cells by 471 and 345%, respectively, compared with the control cells. EPO did not modify the effect of doxorubicin on these cell lines. The results of the present study suggested that EPO was safe for use in combination with doxorubicin in the treatment of patients with breast cancer and concurrent anemia.
  9. Fulltext Synergetic Influence of Bismuth Oxide Nanoparticles, Cisplatin and Baicalein-Rich Fraction on Reactive Oxygen Species Generation and Radiosensitization Effects for Clinical Radiotherapy Beams
    Talik Sisin NN, Abdul Razak K, Zainal Abidin S, Che Mat NF, Abdullah R, Ab Rashid R, et al.
    Int J Nanomedicine, 2020;15:7805-7823.
    PMID: 33116502 DOI: 10.2147/IJN.S269214
    Purpose: This study aimed to quantify synergetic effects induced by bismuth oxide nanoparticles (BiONPs), cisplatin (Cis) and baicalein-rich fraction (BRF) natural-based agent on the reactive oxygen species (ROS) generation and radiosensitization effects under irradiation of clinical radiotherapy beams of photon, electron and HDR-brachytherapy. The combined therapeutic responses of each compound and clinical radiotherapy beam were evaluated on breast cancer and normal fibroblast cell line.

    Methods: In this study, individual BiONPs, Cis, and BRF, as well as combinations of BiONPs-Cis (BC), BiONPs-BRF (BB) and BiONPs-Cis-BRF (BCB) were treated to the cells before irradiation using HDR brachytherapy with 0.38 MeV iridium-192 source, 6 MV photon beam and 6 MeV electron beam. The individual or synergetic effects from the application of the treatment components during the radiotherapy were elucidated by quantifying the ROS generation and radiosensitization effects on MCF-7 and MDA-MB-231 breast cancer cell lines as well as NIH/3T3 normal cell line.

    Results: The ROS generated in the presence of Cis stimulated the most substantial amount of ROS compared to the BiONPs and BRF. Meanwhile, the combination of the components had induced the higher ROS levels for photon beam than the brachytherapy and electron beam. The highest ROS enhancement relative to the control is attributable to the presence of BC combination in MDA-MB-231 cells, in comparison to the BB and BCB combinations. The radiosensitization effects which were quantified using the sensitization enhancement ratio (SER) indicate the highest value by BC in MCF-7 cells, followed by BCB and BB treatment. The radiosensitization effects are found to be more prominent for brachytherapy in comparison to photon and electron beam.

    Conclusion: The BiONPs, Cis and BRF are the potential radiosensitizers that could improve the efficiency of radiotherapy to eradicate the cancer cells. The combination of these potent radiosensitizers might produce multiple effects when applied in radiotherapy. The BC combination is found to have the highest SER, followed by the BCB combination. This study is also the first to investigate the effect of BRF in combination with BiONPs (BB) and BC (BCB) treatments.

  10. The application of naked DNA plasmid (DrZP3) and recombinant adenovirus (Ad-rZP3) in rat animal model to determine comparative efficacy of ZP3-Immunocontraceptive vaccines
    Mohd-Lila MA, Yee LK, Cen LS, Bala JA, Balakrishnan KN, Allaudin ZN, et al.
    Microb Pathog, 2019 Sep;134:103572.
    PMID: 31163251 DOI: 10.1016/j.micpath.2019.103572
    The common physical and chemical methods for controlling rat pest are less than satisfactory and inhumane. Immunocontraception approach has been considered more humane and it can be accomplished by inducing the relevant host immune response that block further development of reproductive gametes. ZP3 proteins are known to play very important role during sperm-ovum fertilization. It is a self-antigen and only localized in female ovaries. Therefore, an immunization with ZP3 protein elsewhere will induce a generalize host immune response against ZP3 protein. This study employed rat ZP3 (rZP3) gene prepared from its cDNA of Rattus rattus diardii. It was delivered and expressed in vivo by naked plamid DNA (DrZP3) or recombinant ZP3-Adenovirus (Ad-rZP3). Expression studies in vitro with DrZP3 or Ad-ZP3 showed rZP3 proteins were successfully expressed in Vero cells. Hyperimmune serum against rZP3 that were prepared by immunizing several rats with purified rZP3-pichia yeast fusion protein showed it blocked sperms from binding DrZP3-transfected Vero cells. Female Sprague Dawley rats immunized with DrZP3 demonstrated a long-term effect for significant reduction of fertility up to 92.6%. Ovaries from rats immunized with DrZP3 were severely atrophied with disappearance of primordial follicles from ovarian cortex with an increased in the amount of oocyte-free cell clusters. Female rats immunized with Ad-rZP3 demonstrated 27% reduction of fertility. The infertility induced by Ad-rZP3 is comparatively low and ineffective. This could be due to a strong host immune response that suppresses the recombinant virus itself resulted in minimum rZP3 protein presentation to the host immune system. As a result, low antibody titers produced against rZP3 is insufficient to block oocytes from maturity and fertilization. Therefore, immunization with DrZP3 for immunocontraception is more effective than Ad-rZP3 recombinant adenovirus. It is proposed to explore further on the use of adenovirus or other alternative viruses to deliver ZP3 protein and for the development of enhanced expression of rZP3 in target host.
  11. Fulltext Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro
    Rahim NFC, Hussin Y, Aziz MNM, Mohamad NE, Yeap SK, Masarudin MJ, et al.
    Molecules, 2021 Feb 26;26(5).
    PMID: 33652694 DOI: 10.3390/molecules26051261
    Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012-2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.
  12. Fulltext Characteristics of Glycerolized Chitosan: NH4NO3-Based Polymer Electrolyte for Energy Storage Devices with Extremely High Specific Capacitance and Energy Density Over 1000 Cycles
    Aziz SB, Brza MA, Brevik I, Hamsan MH, Abdulwahid RT, Majid SR, et al.
    Polymers (Basel), 2020 Nov 17;12(11).
    PMID: 33212879 DOI: 10.3390/polym12112718
    In this work, plasticized polymer electrolyte films consisting of chitosan, ammonium nitrate (NH4NO3) and glycerol for utilization in energy storage devices was presented. Various microscopic, spectroscopic and electrochemical techniques were used to characterize the concerned electrolyte and the electrical double-layer capacitor (EDLC) assembly. The nature of complexation between the polymer electrolyte components was examined via X-ray diffraction analysis. In the morphological study, field emission scanning electron microscopy (FESEM) was used to investigate the impact of glycerol as a plasticizer on the morphology of films. The polymer electrolyte (conducting membrane) was found to have a conductivity of 3.21 × 10-3 S/cm. It is indicated that the number density (n), mobility (μ) and diffusion coefficient (D) of ions are increased with the glycerol amount. The mechanism of charge storing was clarified, which implies a non-Faradaic process. The voltage window of the polymer electrolyte is 2.32 V. It was proved that the ion is responsible for charge-carrying via measuring the transference number (TNM). It was also determined that the internal resistance of the EDLC assembly lay between 39 and 50 Ω. The parameters associated with the EDLC assembly are of great importance and the specific capacitance (Cspe) was determined to be almost constant over 1 to 1000 cycles with an average of 124 F/g. Other decisive parameters were found: energy density (18 Wh/kg) and power density (2700 W/kg).
  13. Fulltext Antitumor and Anti-Metastatic Effects of Citral-Loaded Nanostructured Lipid Carrier in 4T1-Induced Breast Cancer Mouse Model
    Nordin N, Yeap SK, Rahman HS, Zamberi NR, Mohamad NE, Abu N, et al.
    Molecules, 2020 Jun 09;25(11).
    PMID: 32526880 DOI: 10.3390/molecules25112670
    Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T1 breast cancer cells challenged mice. However, the in vivo apoptosis induction and anti-metastatic effects of NLC-Citral have yet to be reported. In this study, the in vitro cytotoxic, anti-migration, and anti-invasion effects of NLC-Citral were tested on 4T1 breast cancer cells. In addition, the in vivo antitumor effects of oral delivery of NLC-Citral was also evaluated on BALB/c mice induced with 4T1 cells. In vitro cytotoxicity results showed that NLC-Citral and citral gave similar IC50 values on 4T1 cells. However, wound healing, migration, and invasion assays reflected better in vitro anti-metastasis potential for NLC-Citral than citral alone. Results from the in vivo study indicated that both NLC-Citral and citral have anti-tumor and anti-metastasis effects, whereby the NLC-Citral showed better efficacy than citral in all experiments. Also, the delay of tumor progression was through the suppression of the c-myc gene expression and induction of apoptosis in the tumor. In addition, the inhibition of metastasis of 4T1 cells to lung and bone marrow by the NLC-Citral and citral treatments was correlated with the downregulation of metastasis-related genes expression including MMP-9, ICAM, iNOS, and NF-kB and the angiogenesis-related proteins including G-CSF alpha, Eotaxin, bFGF, VEGF, IL-1alpha, and M-CSF in the tumor. Moreover, NLC-Citral showed greater downregulation of MMP-9, iNOS, ICAM, Eotaxin, bFGF, VEGF, and M-CSF than citral treatment in the 4T1-challenged mice, which may contribute to the better anti-metastatic effect of the encapsulated citral. This study suggests that NLC is a potential and effective delivery system for citral to target triple-negative breast cancer.
  14. Fulltext Nutritional assessment of pre-school children in rural villages of the family dynamics, lifestyles and nutrition study (1997-2001) I. Socio-economic status of households
    Chee HL, Khor G, Arshad F, Wanmuda W, Shabdin A, Abusamah A, et al.
    Malays J Nutr, 2002 Mar;8(1):13-31.
    PMID: 22692437
    This paper presents the socio-economic profile of households in the Family Dynamics Study (FDS) (1997-2001) and makes comparisons with the earlier Functional Groups Study (FGS) (1992-1996). For the current study, FGS villages with a high prevalence of child malnutrition were purposively selected. In each village selected, all households were included, and interviews with a structured questionnaire were conducted in April-May 1998. Incomes were generally low and incidence of poverty was high; 49.6% of the households were under the poverty line income, of which 37.2% were poor and 12.4% were hard core poor. Overall, only 23.2% of heads of households were in agricultural occupations, others being primarily waged workers and petty traders. Livestock rearing was widespread (57.8%), and most households (90.4%) owned at least one motorised vehicle, the most common being the motorcycle. The majority of households had refrigerators (73.6%), washing machines (58.8%), and televisions (91.1%); but telephones (42.2%), mobile phones (6.1%) and computers (2.3%) were less common. Although 99.7% of households had electricity supply and 95.1% had either a flush or pour flush latrine, only 57.4% had piped water supply. In comparison to the FGS, poverty in the current study is lower (49.6% of FDS households are poor compared to 55.2% of FGS households), the proportion of household heads in agricultural occupations is also lower (26.9% compared to 55.3%), while all other socioeconomic indicators were better, except for piped water supply, which remains inadequate for households in the current study.
  15. Fulltext Clausenidin induces caspase-dependent apoptosis in colon cancer
    Waziri PM, Abdullah R, Yeap SK, Omar AR, Kassim NK, Malami I, et al.
    BMC Complement Altern Med, 2016 Jul 29;16:256.
    PMID: 27473055 DOI: 10.1186/s12906-016-1247-1
    BACKGROUND: Clausena excavata Burm.f. is a shrub traditionally used to treat cancer patients in Asia. The main bioactive chemical components of the plant are alkaloids and coumarins. In this study, we isolated clausenidin from the roots of C. excavata to determine its apoptotic effect on the colon cancer (HT-29) cell line.
    METHOD: We examined the effect of clausenidin on cell viability, ROS generation, DNA fragmentation, mitochondrial membrane potential in HT-29 cells. Ultrastructural analysis was conducted for morphological evidence of apoptosis in the treated HT-29 cells. In addition, we also evaluated the effect of clausenidin treatment on the expression of caspase 3 and 9 genes and proteins in HT-29 cells.
    RESULT: Clausenidin induced a G0/G1 cell cycle arrest in HT-29 cells with significant (p 
  16. Clausenidin from Clausena excavata induces apoptosis in hepG2 cells via the mitochondrial pathway
    Waziri PM, Abdullah R, Yeap SK, Omar AR, Abdul AB, Kassim NK, et al.
    J Ethnopharmacol, 2016 Dec 24;194:549-558.
    PMID: 27729282 DOI: 10.1016/j.jep.2016.10.030
    ETHNOPHARMACOLOGICAL RELEVANCE: Clausena excavata Burm.f. is used locally in folk medicine for the treatment of cancer in South East Asia.

    AIM OF THE STUDY: To determine the mechanism of action of pure clausenidin crystals in the induction of hepatocellular carcinoma (hepG2) cells apoptosis.

    MATERIALS AND METHODS: Pure clausenidin was isolated from Clausena excavata Burm.f. and characterized using (1)H and (13)C NMR spectra. Clausenidin-induced cytotoxicity was determined by MTT assay. The morphology of hepG2 after treatment with clausenidin was determined by fluorescence and Scanning Electron Microscopy. The effect of clausenidin on the apoptotic genes and proteins were determined by real-time qPCR and protein array profiling, respectively. The involvement of the mitochondria in clausenidin-induced apoptosis was investigated using MMP, caspase 3 and 9 assays.

    RESULTS: Clausenidin induced significant (p<0.05) and dose-dependent apoptosis of hepG2 cells. Cell cycle assay showed that clausenidin induced a G2/M phase arrest, caused mitochondrial membrane depolarization and significantly (p<0.05) increased expression of caspases 3 and 9, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, clausenidin caused decreased expression of the anti-apoptotic protein, Bcl 2 and increased expression of the pro-apoptotic protein, Bax. This finding was confirmed by the downregulation of Bcl-2 gene and upregulation of the Bax gene in the treated hepG2 cells.

    CONCLUSION: Clausenidin extracted from Clausena excavata Burm.f. is an anti-hepG2 cell compound as shown by its ability to induce apoptosis through the mitochondrial pathway of apoptosis. Clausenidin can potentially be developed into an anticancer compound.

  17. Fulltext Crude Extracts, Flavokawain B and Alpinetin Compounds from the Rhizome of Alpinia mutica Induce Cell Death via UCK2 Enzyme Inhibition and in Turn Reduce 18S rRNA Biosynthesis in HT-29 Cells
    Malami I, Abdul AB, Abdullah R, Kassim NK, Rosli R, Yeap SK, et al.
    PLoS One, 2017;12(1):e0170233.
    PMID: 28103302 DOI: 10.1371/journal.pone.0170233
    Uridine-cytidine kinase 2 is an enzyme that is overexpressed in abnormal cell growth and its implication is considered a hallmark of cancer. Due to the selective expression of UCK2 in cancer cells, a selective inhibition of this key enzyme necessitates the discovery of its potential inhibitors for cancer chemotherapy. The present study was carried out to demonstrate the potentials of natural phytochemicals from the rhizome of Alpinia mutica to inhibit UCK2 useful for colorectal cancer. Here, we employed the used of in vitro to investigate the effectiveness of natural UCK2 inhibitors to cause HT-29 cell death. Extracts, flavokawain B, and alpinetin compound from the rhizome of Alpinia mutica was used in the study. The study demonstrated that the expression of UCK2 mRNA were substantially reduced in treated HT-29 cells. In addition, downregulation in expression of 18S ribosomal RNA was also observed in all treated HT-29 cells. This was confirmed by fluorescence imaging to measure the level of expression of 18S ribosomal RNA in live cell images. The study suggests the possibility of MDM2 protein was downregulated and its suppression subsequently activates the expression of p53 during inhibition of UCK2 enzyme. The expression of p53 is directly linked to a blockage of cell cycle progression at G0/G1 phase and upregulates Bax, cytochrome c, and caspase 3 while Bcl2 was deregulated. In this respect, apoptosis induction and DNA fragmentation were observed in treated HT-29 cells. Initial results from in vitro studies have shown the ability of the bioactive compounds of flavokawain B and alpinetin to target UCK2 enzyme specifically, inducing cell cycle arrest and subsequently leading to cancer cell death, possibly through interfering the MDM2-p53 signalling pathway. These phenomena have proven that the bioactive compounds could be useful for future therapeutic use in colon cancer.
  18. Fulltext In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells
    Nordin N, Yeap SK, Rahman HS, Zamberi NR, Abu N, Mohamad NE, et al.
    Sci Rep, 2019 02 07;9(1):1614.
    PMID: 30733560 DOI: 10.1038/s41598-018-38214-x
    Very recently, we postulated that the incorporation of citral into nanostructured lipid carrier (NLC-Citral) improves solubility and delivery of the citral without toxic effects in vivo. Thus, the objective of this study is to evaluate anti-cancer effects of NLC-Citral in MDA MB-231 cells in vitro through the Annexin V, cell cycle, JC-1 and fluorometric assays. Additionally, this study is aimed to effects of NLC-Citral in reducing the tumor weight and size in 4T1 induced murine breast cancer model. Results showed that NLC-Citral induced apoptosis and G2/M arrest in MDA MB-231 cells. Furthermore, a prominent anti-metastatic ability of NLC-Citral was demonstrated in vitro using scratch, migration and invasion assays. A significant reduction of migrated and invaded cells was observed in the NLC-Citral treated MDA MB-231 cells. To further evaluate the apoptotic and anti-metastatic mechanism of NLC-Citral at the molecular level, microarray-based gene expression and proteomic profiling were conducted. Based on the result obtained, NLC-Citral was found to regulate several important signaling pathways related to cancer development such as apoptosis, cell cycle, and metastasis signaling pathways. Additionally, gene expression analysis was validated through the targeted RNA sequencing and real-time polymerase chain reaction. In conclusion, the NLC-Citral inhibited the proliferation of breast cancer cells in vitro, majorly through the induction of apoptosis, anti-metastasis, anti-angiogenesis potentials, and reducing the tumor weight and size without altering the therapeutic effects of citral.
  19. Physiological and electroencephalographic changes in goats subjected to transportation, lairage, and slaughter
    Othman AH, Goh YM, Mohamed Mustapha N, Raghazli R, Kaka U, Imlan JC, et al.
    Anim Sci J, 2021 Dec;92(1):e13610.
    PMID: 34390058 DOI: 10.1111/asj.13610
    This preliminary trial investigated the effect of transportation and lairage periods on physiological parameters of goats subjected to slaughter. Nine male Boer cross goats aged 8-12 months were transported for 6 h and kept at lairage for 3, 6, or 16 h (n = 3). Blood samples were collected at pre- (pre-T) and post-transportation (post-T), and post-slaughter (post-S) for determination of hematological parameters, serum enzyme, protein, and cortisol concentrations. Electroencephalogram readings were taken at pre-T, post-T, pre-slaughter (pre-S), and post-S to determine the median frequency (F50 ) and total power (Ptot) values. At post-T, there were manifestations of stress leukogram; increase in hematocrit, total protein, and muscle enzyme concentrations; and decrease in Ptot (p 
  20. Fulltext Characterization and toxicity of citral incorporated with nanostructured lipid carrier
    Nordin N, Yeap SK, Zamberi NR, Abu N, Mohamad NE, Rahman HS, et al.
    PeerJ, 2018;6:e3916.
    PMID: 29312812 DOI: 10.7717/peerj.3916
    The nanoparticle as a cancer drug delivery vehicle is rapidly under investigation due to its promising applicability as a novel drug delivery system for anticancer agents. This study describes the development, characterization and toxicity studies of a nanostructured lipid carrier (NLC) system for citral. Citral was loaded into the NLC using high pressure homogenization methods. The characterizations of NLC-citral were then determined through various methods. Based on Transmission Electron Microscope (TEM) analysis, NLC-Citral showed a spherical shape with an average diameter size of 54.12 ± 0.30 nm and a polydipersity index of 0.224 ± 0.005. The zeta potential of NLC-Citral was -12.73 ± 0.34 mV with an entrapment efficiency of 98.9 ± 0.124%, and drug loading of 9.84 ± 0.041%. Safety profile of the formulation was examined via in vitro and in vivo routes to study its effects toward normal cells. NLC-Citral exhibited no toxic effects towards the proliferation of mice splenocytes. Moreover, no mortality and toxic signs were observed in the treated groups after 28 days of treatment. There were also no significant alterations in serum biochemical analysis for all treatments. Increase in immunomodulatory effects of treated NLC-Citral and Citral groups was verified from the increase in CD4/CD3 and CD8/CD3 T cell population in both NLC-citral and citral treated splenocytes. This study suggests that NLC is a promising drug delivery system for citral as it has the potential in sustaining drug release without inducing any toxicity.
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