Displaying publications 1 - 20 of 36 in total

  1. Edre MA, Azmi MN, Hayati KS, Salmiah MS, Sharifah Norkhadijah SI
    IIUM Medical Journal Malaysia, 2019;18(102):68-0.
    Many studies have shown the effectiveness of educational modules on increasing colorectal cancer screening uptake at individual level but not adjusted for potential clustering effect such as workplace. Longitudinal studies on workplace colorectal cancer screening require a series of analysis under different conditions due to heterogeneity of workplace population. To achieve this, a sensitivity analysis based on Generalized Estimating Equations was conducted to determine the robustness of the predictive performance of health education module in increasing screening uptake. Materials and Method: A parallel, single blind, cluster randomized trial was conducted among 15 organizations in Kuantan, Pahang. Intervention group received a complex Health Education Module comprising of group education, practical session on fecal occult blood test usage and WhatsApp group follow-up, while control group received standard colorectal cancer screening brochure. Sensitivity analyses using intention to treat analysis with interaction term, compatibility term, behavioral intention term and key assumption term were performed. Data were imputed and analysed using generalized estimating equation with IBM SPSS version 23. Pooled adjusted odds ratio was calculated using random effect model with inverse variance weighting using RevMan version 3.5. Results: A total of 166 participants from 15 organizations were recruited in the study. Intervention and control group were comparable at baseline (P>0.05). Health Education Module given in intervention group significantly increased the uptake of FOBT by nearly 5 times compared to control group in sensitivity analyses (pooled adjusted OR=4.60, 95% CI=2.65-7.99, I2=47%, P
  2. Azmi MN, Lokman BS, Ishlah L
    Med J Malaysia, 2006 Mar;61(1):72-5.
    PMID: 16708737 MyJurnal
    A retrospective analysis of 15 cases intracanalicular acoustic neuroma that undergone tumour excision by translabyrinthine approach spanning from August 1996 until December 2002 is presented. The main presenting complaints are unilateral hearing loss (100%) and tinnitus (86.7%). The mean age of presentation was 48.5 years old. Magnetic resonance imaging is the most important investigation tool to diagnose acoustic neuroma. At six months post operatively, the facial nerve was normal or near normal (grade I and II) in 46.6%, grade III to IV in 46.6% and grade V to VI in 6.7% of the cases respectively. There were also four cases of post operative cerebrospinal fluid leak, which was successfully managed with conservative measures. The translabyrinthine approach is the most familiar surgical technique employed by otologist. It is the most direct route to the cerebellopontine angle and internal auditory canal. It requires minimum cerebellar retraction. However, it sacrifices any residual hearing in the operated ear.
  3. Noorlaila B, Zunaina E, Raja-Azmi MN
    PMID: 27800200
    We would like to report two cases of preretinal haemorrhage from two different aetiology courses of bleeding being treated with intravitreal ranibizumab and its outcome. Our first case was a 39-year-old man with a diagnosis of severe aplastic anaemia that presented with bilateral premacular haemorrhages in both eyes. His right eye vision was 6/45 and it was counting finger in the left eye. He was treated with intravitreal ranibizumab once to the right eye and twice to the left eye. Right eye showed complete resolution of premacular haemorrhage and minimal residual premacular haemorrhage in the left eye at 3 months after initial presentation. Our second case was a 32-year-old healthy teacher that presented with preretinal haemorrhage at superotemporal region extending to macular area in left eye secondary to valsalva retinopathy. Her left vision was counting finger. She was treated with single intravitreal ranibizumab to the left eye. There was significant reduction of premacular haemorrhage and her left eye vision improved to 6/6 at 10 weeks after injection. Both cases had favourable outcome with intravitreal ranibizumab and can be considered as nonsurgical treatment option in treating premacular haemorrhage.
  4. Juanarita J, Azmi MN, Azhany Y, Liza-Sharmini AT
    Asian Pac J Trop Biomed, 2012 Sep;2(9):755-6.
    PMID: 23570008 DOI: 10.1016/S2221-1691(12)60223-8
    A 24 year-old Malay lady presented with high grade fever, myalgia, generalized rashes, severe headache and was positive for dengue serology test. Her lowest platelet count was 45 × 10(9) cells/L. She complained of sudden onset of painlessness, profound loss of vision bilaterally 7 days after the onset of fever. On examination, her right eye best corrected vision was 6/30 and left eye was 6/120. Her anterior segment examination was unremarkable. Funduscopy revealed there were multiple retinal haemorrhages found at posterior pole of both fundi and elevation at fovea area with subretinal fluid. Systemic examination revealed normal findings except for residual petechial rashes. She was managed conservatively. Her vision improved tremendously after 2 months. The retinal hemorrhages and foveal elevation showed sign of resolving. Ocular manifestations following dengue fever is rare. However, bilateral visual loss can occur if both fovea are involved.
  5. Asma A, Azmi MN, Mazita A, Marina MB, Salina H, Norlaila M
    PMID: 22468245 DOI: 10.1007/s12070-011-0132-y
    Neuropathy is frequently a late complication of diabetes mellitus. Auditory neuropathy and microangiopathy of inner ear are the possible causes of hearing loss in diabetics. To study the correlation between glycaemic control and hearing threshold in patients with type 2 diabetes mellitus and to determine the differences of hearing threshold between groups treated with different modality. This single blind randomized controlled study was performed at the Department of Medicine and Department of Otorhinolaryngology, Hospital Universiti Kebangsaan Malaysia (UKM) between 1st May 2003 and 31st September 2004. This study was approved by Research Ethics Committee (code number FF-137). Subjects were randomized into two groups. Group 1 were patients treated with conventional oral hypoglycemic agents. The patients in group 2 were those treated with insulin injection. The subjects were seen 4 weekly for 3 months. Audiometric test were performed in all subjects at each visit. Blood were taken for fasting blood glucose, Hb1Ac, and fructosamine at every visit to determine the glycaemic controls of the subject. They were 11 patients (22 ears) treated with oral hypoglycemic agents and 17 patients treated (34 ears) with subcutaneous insulin. There is no significant difference between mean pure tone threshold before and after treatment at all frequencies in both groups. There is also no significance different in fasting glucose level and fructosamine. However, there is significant difference HbA1c levels between the two groups after treatment (P 
  6. Zailani MH, Azmi MN, Deen KI
    Med J Malaysia, 2010 Mar;65(1):66-7.
    PMID: 21265253 MyJurnal
    Faecal incontinence is a debilitating chronic clinical condition which may affect the patient and care givers. Modality of treatment is based on severity of the symptoms as well as the anatomical defect itself, availability of resources and expertise. We describe a modified technique of dynamic graciloplasty as neoanal sphincter for the treatment severe faecal incontinence who has failed previous over lapping sphincteroplasty. In our modified version, instead of using implanted intramuscular electrodes and subcutaneous neurostimulator to provide continuous stimulation, the patient will undergo an external stimulation on the nerve of transplanted gracilis periodically and concurrent biofeedback therapy. We believe the technique is relatively easy to learn and very cost effective without any electrodes or neurostimulator related complications.
  7. Phuah NH, Azmi MN, Awang K, Nagoor NH
    Mol. Cells, 2017 Apr;40(4):291-298.
    PMID: 28401751 DOI: 10.14348/molcells.2017.2285
    MicroRNAs (miRNAs) are short non-coding RNAs that regulate genes posttranscriptionally. Past studies have reported that miR-210 is up-regulated in many cancers including cervical cancer, and plays a pleiotropic role in carcinogenesis. However, its role in regulating response towards anti-cancer agents has not been fully elucidated. We have previously reported that the natural compound 1'S-1'-acetoxychavicol acetate (ACA) is able to induce cytotoxicity in various cancer cells including cervical cancer cells. Hence, this study aims to investigate the mechanistic role of miR-210 in regulating response towards ACA in cervical cancer cells. In the present study, we found that ACA down-regulated miR-210 expression in cervical cancer cells, and suppression of miR-210 expression enhanced sensitivity towards ACA by inhibiting cell proliferation and promoting apoptosis. Western blot analysis showed increased expression of mothers against decapentaplegic homolog 4 (SMAD4), which was predicted as a target of miR-210 by target prediction programs, following treatment with ACA. Luciferase reporter assay confirmed that miR-210 binds to sequences in 3'UTR of SMAD4. Furthermore, decreased in SMAD4 protein expression was observed when miR-210 was overexpressed. Conversely, SMAD4 protein expression increased when miR-210 expression was suppressed. Lastly, we demonstrated that overexpression of SMAD4 augmented the anti-proliferative and apoptosis-inducing effects of ACA. Taken together, our results demonstrated that down-regulation of miR-210 conferred sensitivity towards ACA in cervical cancer cells by targeting SMAD4. These findings suggest that combination of miRNAs and natural compounds could provide new strategies in treating cervical cancer.
  8. Phuah NH, Azmi MN, Awang K, Nagoor NH
    Onco Targets Ther, 2017;10:1695-1705.
    PMID: 28356756 DOI: 10.2147/OTT.S117492
    BACKGROUND: Cervical cancer is the fourth most frequent malignancy affecting women worldwide, but drug resistance and toxicities remain a major challenge in chemotherapy. The use of natural compounds is promising because they are less toxic and able to target multiple signaling pathways. The 1'S-1'-acetoxychavicol acetate (ACA), a natural compound isolated from wild ginger Alpinia conchigera, induced cytotoxicity on various cancer cells including cervical cancer. MicroRNAs (miRNAs) are short noncoding RNAs that regulate numerous biological processes, such as apoptosis and chemosensitivity. Past studies reported that miR-629 is upregulated in many cancers, and its expression was altered in ACA-treated cervical cancer cells. However, the role of miR-629 in regulating sensitivity toward ACA or other anticancer agents has not been reported. Hence, this study aims to investigate the role of miR-629 in regulating response toward ACA on cervical cancer cells.

    METHODS: The miR-629 expression following transfection with miR-629 hairpin inhibitor and hairpin inhibitor negative control was measured using quantitative real-time polymerase chain reaction (RT-qPCR). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate sensitivity toward ACA. Apoptosis was detected using Annexin V/propidium iodide and Caspase 3/7 assays. The gene target for miR-629 was identified using miRNA target prediction programs, luciferase reporter assay and Western blots. Gene overexpression studies were performed to evaluate its role in regulating response toward ACA.

    RESULTS: Transfection with miR-629 hairpin inhibitor downregulated its expression in both cervical cancer cell lines. Suppression of miR-629 increased sensitivity toward ACA by reducing cell proliferation and inducing apoptosis. Luciferase reporter assay confirmed RSU1 as a direct target of miR-629. Overexpression of miR-629 decreased RSU1 protein expression, while inhibition of miR-629 increased RSU1 protein expression. Overexpression of RSU1 augmented antiproliferative and apoptosis-inducing effects of ACA.

    CONCLUSION: Our findings showed that combination of ACA with miR-629 and RSU1 may provide a potential strategy in treating cervical cancer.

  9. Abu Bakar MH, Azmi MN, Shariff KA, Tan JS
    Appl Biochem Biotechnol, 2019 May;188(1):241-259.
    PMID: 30417321 DOI: 10.1007/s12010-018-2920-2
    Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.
  10. In LL, Arshad NM, Ibrahim H, Azmi MN, Awang K, Nagoor NH
    PMID: 23043547 DOI: 10.1186/1472-6882-12-179
    Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1'S-1'-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes.
  11. Phuah NH, In LL, Azmi MN, Ibrahim H, Awang K, Nagoor NH
    Reprod Sci, 2013 May;20(5):567-78.
    PMID: 23012319 DOI: 10.1177/1933719112459220
    The aims of this study were to investigate the combined effects of a natural compound 1'S-1'-acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV-positive human cervical carcinoma cell lines (Ca Ski-low cisplatin sensitivity and HeLa-high cisplatin sensitivity), and to identify microRNAs (miRNAs) modulated in response toward ACA and/or CDDP. It was revealed that both ACA and CDDP induced dose- and time-dependent cytotoxicity when used as a stand-alone agent, while synergistic effects were observed when used in combination with a combination index (CI) value of 0.74 ± 0.01 and 0.85 ± 0.01 in Ca Ski and HeLa cells, respectively. A total of 25 miRNAs were found to be significantly differentially expressed in response to ACA and/or CDDP. These include hsa-miR-138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in signaling pathways regulating apoptosis and cell cycle progression. In conclusion, ACA acts as a chemosensitizer which synergistically potentiates the cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression upon administration of ACA and/or CDDP suggests that miRNAs play an important role in anticancer drug responses, which can be manipulated for therapeutic purposes.
  12. Awang K, Azmi MN, Aun LI, Aziz AN, Ibrahim H, Nagoor NH
    Molecules, 2010 Nov;15(11):8048-59.
    PMID: 21063268 DOI: 10.3390/molecules15118048
    1'-(S)-1'-Acetoxychavicol acetate (ACA) isolated from the Malaysian ethno-medicinal plant Alpinia conchigera Griff. was investigated for its potential as an anticancer drug. In this communication, we describe the cytotoxic and apoptotic properties of ACA on five human tumour cell lines. Data from MTT cell viability assays indicated that ACA induced both time- and dose-dependent cytotoxicity on all tumour cell lines tested and had no adverse cytotoxic effects on normal cells. Total mortality of the entire tumour cell population was achieved within 30 hrs when treated with ACA at 40.0 µM concentration. Flow cytometric analysis for annexin-V and PI dual staining demonstrated that cell death occurred via apoptosis, followed by secondary necrosis. The apoptotic effects of ACA were confirmed via the DNA fragmentation assay, in which consistent laddering of genomic DNA was observed for all tumour cell lines after a 24 hrs post-treatment period at the IC(50) concentration of ACA. A cell cycle analysis using PI staining also demonstrated that ACA induced cell cycle arrest at the G(0)/G(1) phase, corresponding to oral tumour cell lines. In conclusion, ACA exhibits enormous potential for future development as a chemotherapeutic drug against various malignancies.
  13. In LL, Azmi MN, Ibrahim H, Awang K, Nagoor NH
    Anticancer Drugs, 2011 Jun;22(5):424-34.
    PMID: 21346553 DOI: 10.1097/CAD.0b013e328343cbe6
    In this study, the apoptotic mechanism and combinatorial chemotherapeutic effects of the cytotoxic phenylpropanoid compound 1'S-1'-acetoxyeugenol acetate (AEA), extracted from rhizomes of the Malaysian ethnomedicinal plant Alpinia conchigera Griff. (Zingiberaceae), on MCF-7 human breast cancer cells were investigated for the first time. Data from cytotoxic and apoptotic assays such as live and dead and poly-(ADP-ribose) polymerase cleavage assays indicated that AEA was able to induce apoptosis in MCF-7 cells, but not in normal human mammary epithelial cells. A microarray global gene expression analysis of MCF-7 cells, treated with AEA, suggested that the induction of tumor cell death through apoptosis was modulated through dysregulation of the nuclear factor-kappaB (NF-κB) pathway, as shown by the reduced expression of various κB-regulated gene targets. Consequent to this, western blot analysis of proteins corresponding to the NF-κB pathway indicated that AEA inhibited phosphorylation levels of the inhibitor of κB-kinase complex, resulting in the elimination of apoptotic resistance originating from NF-κB activation. This AEA-based apoptotic modulation was elucidated for the first time in this study, and gave rise to the proposal of an NF-κB model termed the 'Switching/Alternating Model.' In addition to this, AEA was also found to synergistically enhance the proapoptotic effects of paclitaxel, when used in combination with MCF-7 cells, presumably by a chemosensitizing role. Therefore, it was concluded that AEA isolated from the Malaysian tropical ginger (A. conchigera) served as a very promising candidate for further in-vivo development in animal models and in subsequent clinical trials involving patients with breast-related malignancies.
  14. Hasima N, Aun LI, Azmi MN, Aziz AN, Thirthagiri E, Ibrahim H, et al.
    Phytomedicine, 2010 Oct;17(12):935-9.
    PMID: 20729047 DOI: 10.1016/j.phymed.2010.03.011
    Medicinal plants containing active natural compounds have been used as an alternative treatment for cancer patients in many parts of the world especially in Asia (Itharat et al. 2004). In this report, we describe the cytotoxic and apoptotic properties of 1'S-1'-acetoxyeugenol acetate (AEA), an analogue of 1'S-1'-acetoxychavicol acetate (ACA), isolated from the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) on human breast cancer cells. Data from MTT cell viability assays indicated that AEA induced both time- and dose-dependent cytotoxicity with an IC(50) value of 14.0 μM within 36 h of treatment on MCF-7 cells, but not in HMEC normal control cells. Both annexin V-FITC/PI flow cytometric analysis and DNA fragmentation assays confirmed that AEA induced cell death via apoptosis. AEA was also found to induce cell cycle arrest in MCF-7 cells at the G(0)/G(1) phase with no adverse cell cycle arrest effects on HMEC normal control cells. It was concluded that AEA isolated from the Malaysian tropical ginger represents a potential chemotherapeutic agent against human breast cancer cells with higher cytotoxicity potency than its analogue, ACA.
  15. Azmi MN, Péresse T, Remeur C, Chan G, Roussi F, Litaudon M, et al.
    Fitoterapia, 2016 Mar;109:190-5.
    PMID: 26779944 DOI: 10.1016/j.fitote.2016.01.004
    A phytochemical study of the EtOAc-soluble part of the methanolic extract of the bark of Endiandra kingiana led to the isolation of three new pentacyclic kingianins as racemic mixtures, kingianins O-Q (1-3), together with the known kingianins A, F, K, L, M and N (4-9), respectively. The structures of the new kingianins 1-3 were determined by 1D and 2D NMR analysis in combination with HRESIMS experiments. Kingianins A-Q were assayed for Mcl-1 binding affinity. Kingianins G and H were found to be potent inhibitors of Mcl-1/Bid interaction. A structure-activity relationship study showed that potency is very sensitive to the substitution pattern on the pentacyclic core. In addition, in contrast with the binding affinity for Bcl-xL, the levorotatory enantiomers of kingianins G, H and J exhibited similar binding affinities for Mcl-1 than their dextrorotatory counterparts, indicating that the two anti-apoptotic proteins have slightly different binding profiles.
  16. Wong KT, Osman H, Parumasivam T, Supratman U, Che Omar MT, Azmi MN
    Molecules, 2021 Apr 05;26(7).
    PMID: 33916423 DOI: 10.3390/molecules26072081
    A total of fourteen pyrazoline derivatives were synthesized through cyclo-condensation reactions by chalcone derivatives with different types of semicarbazide. These compounds were characterized by IR, 1D-NMR (1H, 13C and Distortionless Enhancement by Polarization Transfer - DEPT-135) and 2D-NMR (COSY, HSQC and HMBC) as well as mass spectroscopy analysis (HRMS). The synthesized compounds were tested for their antituberculosis activity against Mycobacterium tuberculosis H37Ra in vitro. Based on this activity, compound 4a showed the most potent inhibitory activity, with a minimum inhibitory concentration (MIC) value of 17 μM. In addition, six other synthesized compounds, 5a and 5c-5g, exhibited moderate activity, with MIC ranges between 60 μM to 140 μM. Compound 4a showed good bactericidal activity with a minimum bactericidal concentration (MBC) value of 34 μM against Mycobacterium tuberculosis H37Ra. Molecular docking studies for compound 4a on alpha-sterol demethylase was done to understand and explore ligand-receptor interactions, and to hypothesize potential refinements for the compound.
  17. Abdul-Salim I, Embong Z, Khairy-Shamel ST, Raja-Azmi MN
    Clin Ophthalmol, 2013;7:703-6.
    PMID: 23589678 DOI: 10.2147/OPTH.S42208
    Herein, we report our experience in treating extensive traumatic submacular hemorrhage with a single dose of intravitreal ranibizumab. A 23-year-old healthy Malay man presented with a progressive reduction of central vision in the left eye of 2 days' duration following a history of blunt trauma. Visual acuity was reduced to counting fingers. Examination revealed infero-temporal subconjunctival hemorrhage, traumatic anterior uveitis, and an extensive sub-macular hemorrhage with suspicion of a choroidal rupture in the affected eye. He was initially treated conservatively with topical prednisolone acetate 1%. The subconjunctival hemorrhage and anterior uveitis resolved but his vision remained poor with minimal resolution of the submacular hemorrhage at 1 week follow-up (day 12 post-trauma). In view of the poor resolution of submacular hemorrhage, he was treated with a single dose of 0.5 mg intravitreal ranibizumab at day 20 post-trauma. At 4 weeks post-intravitreal ranibizumab, there was an improvement in visual acuity (from counting fingers to 6/45) and complete resolution of the submacular hemorrhage with presence of a choroidal rupture scar temporal to the fovea, which was not seen clearly at presentation due to obscuration by blood. His visual acuity further improved to 6/18 at 3 months post-trauma. Although this single case had a favorable outcome, a large population cohort study is needed to establish the effectiveness of intravitreal ranibizumab in treating extensive traumatic submacular hemorrhage.
  18. Guan-Fook N, Hayati AA, Raja-Azmi MN, Liza-Sharmini AT, Wan-Hazabbah WH, Zunaina E
    Clin Ophthalmol, 2012;6:487-90.
    PMID: 22536041 DOI: 10.2147/OPTH.S29806
    We report a case of diffuse unilateral subacute neuroretinitis in a young boy with no clinical visualization of nematode. The diagnosis was made based on clinical findings and detection of Toxocara immunoglobulin G by Western blot test. An 11-year-old Malay boy presented with progressive blurring of vision in the left eye for a duration of 1 year. It was associated with intermittent floaters. Visual acuity in the left eye was 6/45 and improved to 6/24 with pinhole. There was positive relative afferent pupillary defect, impaired color vision, and presence of red desaturation in the left eye. There were occasional cells in the anterior chamber with no conjunctiva injection. Posterior segment examination revealed mild-to-moderate vitritis and generalized pigmentary changes of the retina with attenuated vessels. The optic disk was slightly hyperemic with mild edema. There was presence of multiple, focal, gray-white subretinal lesions at the inferior part of the retina. Full blood picture results showed eosinophilia with detection of Toxocara immunoglobulin G by Western blot test. Investigations for other infective causes and connective tissue diseases were negative. The diagnosis of diffuse unilateral subacute neuroretinitis secondary to Toxocara was made based on clinical findings and laboratory results. He was treated with oral albendazole 400 mg daily for 5 days and oral prednisolone 1 mg/kg with tapering doses over 6 weeks. At 1 month follow-up, the inflammation had reduced, and multiple, focal, gray-white subretinal lesions were resolved; however there was no improvement of vision.
  19. Sok SP, Arshad NM, Azmi MN, Awang K, Ozpolat B, Hasima Nagoor N
    PLoS One, 2017;12(2):e0171329.
    PMID: 28158287 DOI: 10.1371/journal.pone.0171329
    Autophagy plays a role in deciding the fate of cells by inducing either survival or death. 1'S-1-acetoxychavicol acetate (ACA) is a phenylpropanoid isolated from rhizomes of Alpinia conchigera and has been reported previously on its apoptotic effects on various cancers. However, the effect of ACA on autophagy remains ambiguous. The aims of this study were to investigate the autophagy-inducing ability of ACA in human non-small cell lung cancer (NSCLC), and to determine its role as pro-survival or pro-death mechanism. Cell viability assay was conducted using MTT. The effect of autophagy was assessed by acridine orange staining, GFP-LC3 punctate formation assay, and protein level were analysed using western blot. Annexin V-FITC/PI staining was performed to detect percentage of cells undergoing apoptosis by using flow cytometry. ACA inhibits the cell viability and induced formation of cytoplasmic vacuoles in NSCLC cells. Acidic vesicular organelles and GFP-LC3 punctate formation were increased in response to ACA exposure in A549 and SK-LU-1 cell lines; implying occurrence of autophagy. In western blot, accumulation of LC3-II accompanied by degradation of p62 was observed, which further confirmed the full flux of autophagy induction by ACA. The reduction of Beclin-1 upon ACA treatment indicated the Beclin-1-independent autophagy pathway. An early autophagy inhibitor, 3-methyaldenine (3-MA), failed to suppress the autophagy triggered by ACA; validating the existence of Beclin-1-independent autophagy. Silencing of LC3-II using short interfering RNA (siRNA) abolished the autophagy effects, enhancing the cytotoxicity of ACA through apoptosis. This proposed ACA triggered a pro-survival autophagy in NSCLC cells. Consistently, co-treatment with lysosomal inhibitor, chloroquine (CQ), exerted a synergistic effect resulting in apoptosis. Our findings suggested ACA induced pro-survival autophagy through Beclin-1-independent pathway in NSCLC. Hence, targeting autophagy pathway using autophagy inhibitor such as CQ represented a novel promising approach to potentiate the cytotoxicity of ACA through apoptosis in NSCLC.
  20. Al-Refai M, Ibrahim MM, Azmi MN, Osman H, Bakar MHA, Geyer A
    Molecules, 2019 Nov 10;24(22).
    PMID: 31717690 DOI: 10.3390/molecules24224072
    A series of 2-methoxypyridine-3-carbonitrile (5a-i)-bearing aryl substituents were successfully synthesized in good yields by the condensation of chalcones (4a-i) with malononitrile in basic medium. The condensation process, in most cases, offers a route to a variety of methoxypyridine derivatives (6a-g) as side products in poor yields. All new compounds were fully characterized using different spectroscopic methods. Mass ESI-HMRS measurements were also performed. Furthermore, these compounds were screened for their in vitro cytotoxicity activities against three cancer cell lines; namely, those of the liver (line HepG2), prostate (line DU145) and breast (line MBA-MB-231). The cytotoxicity assessment revealed that compounds 5d, 5g, 5h and 5i exhibit promising antiproliferative effects (IC50 1-5 µM) against those three cancer cell lines.
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links