Displaying publications 161 - 180 of 1087 in total

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  1. Cell death induced by hydroxyapatite on L929 fibroblast cells
    Inayat-Hussain SH, Rajab NF, Roslie H, Hussin AA, Ali AM, Annuar BO
    Med J Malaysia, 2004 May;59 Suppl B:176-7.
    PMID: 15468875
    Biomaterials intended for end-use application as bone-graft substitutes have to undergo safety evaluation. In this study, we investigated the in vitro cytotoxic effects especially to determine the mode of death of two hydroxyapatite compounds (HA2, HA3) which were synthesized locally. The methods used for cytotoxicity was the standard MTT assay whereas AO/PI staining was performed to determine the mode of cell death in HA treated L929 fibroblasts. Our results demonstrated that both HA2 and HA3 were not significantly cytotoxic as more than 75% cells after 72 hours treatment were viable. Furthermore, we found that the major mode of cell death in HA treated cells was apoptosis. In conclusion, our results demonstrated that these hydroxyapatite compounds are not cytotoxic where the mode of death was primarily via apoptosis.
    Matched MeSH terms: Apoptosis/drug effects
  2. Fulltext Apoptosis in endometria of dysfuntional uterine bleeding women
    Rekha K, Malini A, Xavier R, Baba K
    Med J Malaysia, 2005 Mar;60(1):41-5.
    PMID: 16250278
    The study of apoptosis in endometrium of women with irregular uterine bleeding and its predictive value in endometrial malignancy. Analyze apoptotic and mitotic indices and their relevance in irregular uterine bleeding. To determine the expression of Bcl-2 oncoprotein in endometrial glands from patients with irregular uterine bleeding. Department of pathology in a Government Hospital serving a varied socio-economic population in Chennai. Random samples of endometrial currettings from dysfunctional uterine bleeding (DUB) patient who underwent endometrial curettage as therapeutic and diagnostic procedure during the year 2000. Of 50 cases of endometrial samples from patients diagnosed as cases of DUB, the apoptotic and mitotic indexing was carried out and histological categorization revealed 13 cases as Anovulatory. 14 as simple hyperplasia, 5 as early secretory endometrium, 4 as mid secretory and 4 as late secretory endometrium and 7 as endometrium showing features of hormonal imbalance. Three cases were not included, due to sub-optimal processing. A good correlation of the Bcl-2 expression and the apoptotic cell morphology/indices, in the different categories of the endometria of DUB cases is observed. This preliminary study gives an insight to the existence of a correlative pattern of apoptosis in DUB cases. A prospective study on a larger number of cases may substantiate the hypothesis that the Apoptotic and Mitotic indices are useful screening methods with predictive values on development of endometrial carcinoma. It is observed that an increased apoptotic index correlating with high Bcl-2 expression, reflecting the actual cell burden. This prolonged cell survival resisting cell deletion is associated with irregular uterine bleeding endometria.
    Matched MeSH terms: Apoptosis/physiology*
  3. Enterovirus 71 infection induces apoptosis in Vero cells
    Chan YF, Abubakar S
    Malays J Pathol, 2003 Jun;25(1):29-35.
    PMID: 16196375
    The effects of Enterovirus 71 (HEV71) infection on African green monkey kidney cells (Vero) were investigated. It was found that the infected cells showed progressive cellular morphological changes characteristic in apoptotic cells within 10 hours post-infection. The number of apoptotic cells correlated significantly with the number of HEV71 antigen positive cells when cells were labeled using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and stained for HEV71 antigen. Approximately 11, 26, 45 and 50% of the infected cells were apoptotic at 12, 24, 48 and 72 hours post-infection, respectively. Internucleosomal DNA fragmentation, characteristic in the late stage of apoptosis was noted beginning on day 2 post-infection. The DNA fragmentation, however, was absent in cells treated with the heat- and ultraviolet light-inactivated virus inocula. These results demonstrate the capacity of HEV71 to induce apoptosis in the infected cells. The induction, however, requires high level of HEV71 infectivity and the presence of live virus particles, suggesting the need for the presence of specific viral proteins for apoptosis to occur.
    Matched MeSH terms: Apoptosis/physiology*
  4. Genetic susceptibility to cervical cancer: role of common polymorphisms in apoptosis-related genes
    Tan SC, Ankathil R
    Tumour Biol., 2015 Sep;36(9):6633-44.
    PMID: 26242271 DOI: 10.1007/s13277-015-3868-2
    Cervical cancer is a common malignancy which poses a significant health burden among women, especially those living in the developing countries. Although human papillomavirus (HPV) infection has been unequivocally implicated in the etiopathogenesis of the cancer, it alone is not adequate to contribute to the malignant transformation of cervical cells. Most HPV infections regress spontaneously, and only a small proportion of women have persistent infections which eventually lead to malignancy. This suggests that interplays between HPV infection and other cofactors certainly exist during the process of cervical carcinogenesis, which synergistically contribute to the differential susceptibility of an individual to the malignancy. Undoubtedly, host genetic factors represent a major element involved in such a synergistic interaction, and accumulating evidence suggests that polymorphisms in apoptosis-related genes play an important role in the genetic susceptibility to cervical cancer. This review consolidates the recent literatures on the role of common polymorphisms in apoptosis-related genes in genetic susceptibility to cervical cancer.
    Matched MeSH terms: Apoptosis/genetics*
  5. Fulltext Inhibitory and apoptosis-inducing effects of Newcastle disease virus strain AF2240 on mammary carcinoma cell line
    Ahmad U, Ahmed I, Keong YY, Abd Manan N, Othman F
    Biomed Res Int, 2015;2015:127828.
    PMID: 25821783 DOI: 10.1155/2015/127828
    Breast cancer is the malignant tumour that developed from cells of the breast and is the first leading cause of cancer death among women worldwide. Surgery, radiotherapy, and chemotherapy are the available treatments for breast cancer, but these were reported to have side effects. Newcastle disease virus (NDV) known as Avian paramyxovirus type-1 (APMV1) belongs to the genus Avulavirus in a family Paramyxoviridae. NDV is shown to be a promising anticancer agent, killing tumour cells while sparing normal cells unharmed. In this study, the oncolytic and cytotoxic activities of NDV AF2240 strain were evaluated on MDA-MB-231, human mammary carcinoma cell line, using MTT assay, and its inhibitory effects were further studied using proliferation and migration assays. Morphological and apoptotic-inducing effects of NDV on MD-MB-231 cells were observed using phase contrast and fluorescence microscopes. Detection of DNA fragmentation was done following terminal deoxyribonucleotide transferase-mediated Br-dUTP nick end labeling staining (TUNEL) assay, which confirmed that the mode of death was through apoptosis and was quantified by flow cytometry. Furthermore, analysis of cellular DNA content demonstrated that the virus caused an increase in the sub-G1 phase (apoptotic peak) of the cell cycle. It appears that NDV AF2240 strain is a potent anticancer agent that induced apoptosis in time-dependent manner.
    Matched MeSH terms: Apoptosis*
  6. Fulltext Induction of apoptosis in neurogenic pulmonary edema
    Abu Bakar S, Shafee N, Chee HY
    Med J Malaysia, 1999 Sep;54(3):402-3.
    PMID: 11045072
    Matched MeSH terms: Apoptosis/physiology*
  7. Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells
    Inayat-Hussain SH, Annuar BO, Din LB, Ali AM, Ross D
    Toxicol In Vitro, 2003 Aug;17(4):433-9.
    PMID: 12849726
    Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.
    Matched MeSH terms: Apoptosis/physiology*
  8. Altholactone, a novel styryl-lactone induces apoptosis via oxidative stress in human HL-60 leukemia cells
    Inayat-Hussain SH, Osman AB, Din LB, Taniguchi N
    Toxicol Lett, 2002 May 28;131(3):153-9.
    PMID: 11992734
    Plant styryl-lactone derivatives isolated from Goniothalamus sp. are potential compounds for cancer chemotherapy. In this study, we have examined the mechanisms of apoptosis induced by altholactone, a stryl-lactone isolated from the Malaysian plant G. malayanus on human HL-60 promyelocytic leukemia cells. Flow cytometric analysis of the externalization of phosphatidylserine (PS) using the annexin V/PI method on altholactone treated HL-60 cells showed a concentration-dependent increase of apoptosis from concentrations ranging from 10.8 (2.5 microg/ml) to 172.4 microM (40 microg/ml). Pre-treatment with the antioxidant N-acetylcysteine (1 mM) completely abrogated apoptosis induced by altholactone, suggesting for the involvement of oxidative stress. Further flow cytometric assessment of the level of intracellular peroxides using the fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA) confirmed that altholactone induced an increase in cellular oxidative stress in HL-60 cells which was suppressed by N-acetylcysteine. In summary, our results demonstrate for the first time that altholactone induced apoptosis in HL-60 cells occurs via oxidative stress.
    Matched MeSH terms: Apoptosis/drug effects*
  9. Fulltext Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells
    Chuah LO, Foo HL, Loh TC, Mohammed Alitheen NB, Yeap SK, Abdul Mutalib NE, et al.
    BMC Complement Altern Med, 2019 Jun 03;19(1):114.
    PMID: 31159791 DOI: 10.1186/s12906-019-2528-2
    BACKGROUND: Lactobacillus plantarum, a major species of Lactic Acid Bacteria (LAB), are capable of producing postbiotic metabolites (PM) with prominent probiotic effects that have been documented extensively for rats, poultry and pigs. Despite the emerging evidence of anticancer properties of LAB, very limited information is available on cytotoxic and antiproliferative activity of PM produced by L. plantarum. Therefore, the cytotoxicity of PM produced by six strains of L. plantarum on various cancer and normal cells are yet to be evaluated.

    METHODS: Postbiotic metabolites (PM) produced by six strains of L. plantarum were determined for their antiproliferative and cytotoxic effects on normal human primary cells, breast, colorectal, cervical, liver and leukemia cancer cell lines via MTT assay, trypan blue exclusion method and BrdU assay. The toxicity of PM was determined for human and various animal red blood cells via haemolytic assay. The cytotoxicity mode was subsequently determined for selected UL4 PM on MCF-7 cells due to its pronounced cytotoxic effect by fluorescent microscopic observation using AO/PI dye reagents and flow cytometric analyses.

    RESULTS: UL4 PM exhibited the lowest IC50 value on MCF-7, RG14 PM on HT29 and RG11 and RI11 PM on HL60 cell lines, respectively from MTT assay. Moreover, all tested PM did not cause haemolysis of human, dog, rabbit and chicken red blood cells and demonstrated no cytotoxicity on normal breast MCF-10A cells and primary cultured cells including human peripheral blood mononuclear cells, mice splenocytes and thymocytes. Antiproliferation of MCF-7 and HT-29 cells was potently induced by UL4 and RG 14 PM respectively after 72 h of incubation at the concentration of 30% (v/v). Fluorescent microscopic observation and flow cytometric analyses showed that the pronounced cytotoxic effect of UL4 PM on MCF-7 cells was mediated through apoptosis.

    CONCLUSION: In conclusion, PM produced by the six strains of L. plantarum exhibited selective cytotoxic via antiproliferative effect and induction of apoptosis against malignant cancer cells in a strain-specific and cancer cell type-specific manner whilst sparing the normal cells. This reveals the vast potentials of PM from L. plantarum as functional supplement and as an adjunctive treatment for cancer.

    Matched MeSH terms: Apoptosis/drug effects
  10. Identification and Quantification of Quercetin, A Major Constituent of Artocarpus altilis by Targeting Related Genes of Apoptosis and Cell Cycle: In Vitro Cytotoxic Activity Against Human Lung Carcinoma Cell Lines
    Jalal TK, Khan AYF, Natto HA, Abdull Rasad MSB, Arifin Kaderi M, Mohammad M, et al.
    Nutr Cancer, 2019;71(5):792-805.
    PMID: 30614285 DOI: 10.1080/01635581.2018.1516790
    Nine phenolic compounds were identified and quantified in Artocarpus altilia fruit. One of the main compounds was quercetin, which is the major class of flavonoids has been identified and quantified in pulp part of A. altilis fruit of methanol extract. The aim of this study was to evaluate in vitro cytotoxic assay. Inhibitory concentration 50% concentration was determined using trypan blue exclusion assay. Apoptosis induction and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell cycle-related regulatory genes were assessed by RT-qPCR study of the methanol extract of pulp part on human lung carcinoma (A549) cell line. A significant increase of cells at G2/M phases was detected (P 
    Matched MeSH terms: Apoptosis/drug effects*
  11. Pharmacological Effects of Melatonin as Neuroprotectant in Rodent Model: A Review on the Current Biological Evidence
    Tan HY, Ng KY, Koh RY, Chye SM
    Cell Mol Neurobiol, 2020 Jan;40(1):25-51.
    PMID: 31435851 DOI: 10.1007/s10571-019-00724-1
    The progressive loss of structure and functions of neurons, including neuronal death, is one of the main factors leading to poor quality of life. Promotion of functional recovery of neuron after injury is a great challenge in neuroregenerative studies. Melatonin, a hormone is secreted by pineal gland and has antioxidative, anti-inflammatory, and anti-apoptotic properties. Besides that, melatonin has high cell permeability and is able to cross the blood-brain barrier. Apart from that, there are no reported side effects associated with long-term usage of melatonin at both physiological and pharmacological doses. Thus, in this review article, we summarize the pharmacological effects of melatonin as neuroprotectant in central nervous system injury, ischemic-reperfusion injury, optic nerve injury, peripheral nerve injury, neurotmesis, axonotmesis, scar formation, cell degeneration, and apoptosis in rodent models.
    Matched MeSH terms: Apoptosis/drug effects
  12. DNA fragmentation, an indicator of apoptosis, in cultured black tiger shrimp Penaeus monodon infected with white spot syndrome virus (WSSV)
    Sahtout AH, Hassan MD, Shariff M
    Dis Aquat Organ, 2001 Mar 9;44(2):155-9.
    PMID: 11324818
    Fifty black tiger shrimp Penaeus monodon from commercial cultivation ponds in Malaysia were examined by Tdt-mediated dUTP nick-end labeling (TUNEL) fluorescence assay and agarose gel electrophoresis of DNA extracts for evidence of DNA fragmentation as an indicator of apoptosis. From these specimens, 30 were grossly normal and 20 showed gross signs of white spot syndrome virus (WSSV) infection. Of the 30 grossly normal shrimp, 5 specimens were found to be positive for WSSV infection by normal histology and by nested polymerase chain reaction (PCR) analysis. All of the specimens showing gross signs of WSSV infection were positive for WSSV by normal histology, while 5 were positive by nested PCR only (indicating light infections) and 15 were positive by 1-step PCR (indicating heavy infections). Typical histological signs of WSSV infection included nuclear hypertrophy, chromatin condensation and margination. None of the 25 grossly normal shrimp negative for WSSV by 1-step PCR showed any signs of DNA fragmentation by TUNEL assay or agarose gel electrophoresis of DNA extracts. The 10 specimens that gave PCR-positive results for WSSV by nested PCR only (i.e., 5 grossly normal shrimp and 5 grossly positive for WSSV) gave mean counts of 16 +/- 8% TUNEL-positive cells, while the 25 specimens PCR positive by 1-step PCR gave mean counts of 40 +/- 7% TUNEL-positive cells. Thus, the number of TUNEL positive cells present in tissues increased with increasing severity of infection, as determined by gross signs of white spots on the cuticle, the number of intranuclear inclusions in histological sections, and results from single and nested PCR assays. DNA extracts of PCR-positive specimens tested by agarose gel electrophoresis showed indications of DNA fragmentation either as smears or as 200 bp ladders. Given that DNA fragmentation is generally considered to be a hallmark of apoptosis, the results suggested that apoptosis might be implicated in shrimp death caused by WSSV.
    Matched MeSH terms: Apoptosis/genetics*
  13. Fulltext The Curcumin Analogue, MS13 (1,5-Bis(4-hydroxy-3- methoxyphenyl)-1,4-pentadiene-3-one), Inhibits Cell Proliferation and Induces Apoptosis in Primary and Metastatic Human Colon Cancer Cells
    Ismail NI, Othman I, Abas F, H Lajis N, Naidu R
    Molecules, 2020 Aug 20;25(17).
    PMID: 32825505 DOI: 10.3390/molecules25173798
    The cytotoxic and apoptotic effects of turmeric (Curcuma longa) on colon cancer have been well documented but specific structural modifications of curcumin have been shown to possess greater growth-suppressive potential on colon cancer than curcumin. Therefore, the aim of this study is to identify the anti-cancer properties of curcumin analogue-MS13, a diarylpentanoid on the cytotoxicity, anti-proliferative and apoptotic activity of primary (SW480) and metastatic (SW620) human colon cancer cells. A cell viability assay showed that MS13 has greater cytotoxicity effect on SW480 (EC50: 7.5 ± 2.8 µM) and SW620 (EC50: 5.7 ± 2.4 µM) compared to curcumin (SW480, EC50: 30.6 ± 1.4 µM) and SW620, EC50: 26.8 ± 2.1 µM). Treatment with MS13 at two different doses 1X EC50 and 2X EC50 suppressed the colon cancer cells growth with lower cytotoxicity against normal cells. A greater anti-proliferative effect was also observed in MS13 treated colon cancer cells compared to curcumin at 48 and 72 h. Subsequent analysis on the induction of apoptosis showed that MS13 treated cells exhibited morphological features associated with apoptosis. The findings are also consistent with cellular apoptotic activities shown by increased caspase-3 activity and decreased Bcl-2 protein level in both colon cancer cell lines. In conclusion, MS13 able to suppress colon cancer cell growth by inhibiting cell proliferation and induce apoptosis in primary and metastatic human colon cancer cells.
    Matched MeSH terms: Apoptosis/drug effects*
  14. Fulltext Annexin A1: A Bane or a Boon in Cancer? A Systematic Review
    Ganesan T, Sinniah A, Ibrahim ZA, Chik Z, Alshawsh MA
    Molecules, 2020 Aug 14;25(16).
    PMID: 32823805 DOI: 10.3390/molecules25163700
    Annexin A1 has been extensively investigated as an anti-inflammatory protein, but its role in different types of cancer has not been consolidated in a single systematic review to date. Thus, the aim of this paper is to systematically review and critically analyse 18 studies (in-vivo and in-vitro) to consolidate, in a concerted manner, all the information on differential expression of Annexin A1 in different types of cancer and the role this protein plays in tumorigenesis. Pubmed, Scopus, Web of Science, and ScienceDirect were used for the literature search and the keywords used are "annexin A1," "lipocortin 1," "cancer," "malignancy," "neoplasm," "neoplasia," and "tumor." A total of 1128 articles were retrieved by implementing a standard search strategy subjected to meticulous screening processes and 442 articles were selected for full article screening. A total of 18 articles that adhered to the inclusion criteria were included in the systematic review and these articles possessed low to moderate bias. These studies showed a strong correlation between Annexin A1 expression and cancer progression via modulation of various cancer-associated pathways. Differential expression of Annexin A1 is shown to play a role in cellular proliferation, metastasis, lymphatic invasion, and development of resistance to anti-cancer treatment. Meta-analysis in the future may provide a statistically driven association between Annexin A1 expression and malignancy progression.
    Matched MeSH terms: Apoptosis*
  15. Fulltext Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma
    Buskaran K, Bullo S, Hussein MZ, Masarudin MJ, Mohd Moklas MA, Fakurazi S
    Materials (Basel), 2021 Feb 09;14(4).
    PMID: 33572054 DOI: 10.3390/ma14040817
    Liver cancer is listed as the fifth-ranked cancer, responsible for 9.1% of all cancer deaths globally due to its assertive nature and poor survival rate. To overcome this obstacle, efforts have been made to ensure effective cancer therapy via nanotechnology utilization. Recent studies have shown that functionalized graphene oxide (GO)-loaded protocatechuic acid has shown some anticancer activities in both passive and active targeting. The nanocomposites' physicochemical characterizations were conducted. A lactate dehydrogenase experiment was conducted to estimate the severity of cell damage. Subsequently, a clonogenic assay was carried out to examine the colony-forming ability during long-term exposure of the nanocomposites. The Annexin V/ propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Following the intervention of nanocomposites, cell cycle arrest was ascertained at G2/M phase. There was depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. Finally, the proteomic profiling array and quantitative reverse transcription polymerase chain reaction revealed the expression of pro-apoptotic and anti-apoptotic proteins induced by graphene oxide conjugated PEG loaded with protocatechuic acid drug folic acid coated nanocomposite (GOP-PCA-FA) in HepG2 cells. In conclusion, GOP-PCA-FA nanocomposites treated HepG2 cells exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid and GOP-PCA nanocomposites, due to the utilization of a folic acid-targeting nanodrug delivery system.
    Matched MeSH terms: Apoptosis; Apoptosis Regulatory Proteins
  16. Role of vacuolating cytotoxin A in Helicobacter pylori infection and its impact on gastric pathogenesis
    Ansari S, Yamaoka Y
    Expert Rev Anti Infect Ther, 2020 10;18(10):987-996.
    PMID: 32536287 DOI: 10.1080/14787210.2020.1782739
    Introduction Helicobacter pylori causes, via the influence of several virulence factors, persistent infection of the stomach, which leads to severe complications. Vacuolating cytotoxin A (VacA) is observed in almost all clinical strains of H. pylori; however, only some strains produce the toxigenic and pathogenic VacA, which is influenced by the gene sequence variations. VacA exerts its action by causing cell vacuolation and apoptosis. We performed a PubMed search to review the latest literatures published in English language. Areas covered Articles regarding H. pylori VacA and its genotypes, architecture, internalization, and role in gastric infection and pathogenicity are reviewed. We included the search for recently published literature until January 2020. Expert opinion H. pylori VacA plays a crucial role in severe gastric pathogenicity. In addition, VacA mediated in vivo bacterial survival leads to persistent infection and an enhanced bacterial evasion from the action of antibiotics and the innate host defense system, which leads to drug evasion. VacA as a co-stimulator for the CagA phosphorylation may exert a synergistic effect playing an important role in the CagA-mediated pathogenicity.
    Matched MeSH terms: Apoptosis/physiology
  17. Fulltext Molecular Docking Study of Naturally Derived Flavonoids with Antiapoptotic BCL-2 and BCL-XL Proteins toward Ovarian Cancer Treatment
    Abd Ghani MF, Othman R, Nordin N
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S676-S680.
    PMID: 33828360 DOI: 10.4103/jpbs.JPBS_272_19
    The naturally derived flavonoids are well known to have anticarcinogenic effects. Flavonoids could be an alternative strategy for ovarian cancer treatment, due to existing platinum-based drugs are reported to develop resistance with low survival rates. Inhibition of antiapoptotic proteins, namely B-cell lymphoma (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), is the key target to stimulate apoptosis process in cancer cells. This study aimed to determine the binding interaction of five naturally derived flavonoids (biochanin A, myricetin, apigenin, galangin, and fisetin) with potential antiapoptotic target proteins (Bcl-2 and Bcl-xl). The molecular docking study was conducted using AutoDock Vina program. The binding affinity and the presence of hydrogen bonds between the flavonoids and target proteins were predicted. Our findings showed that all the flavonoids showed better binding affinity with Bcl-xl than that of Bcl-2 proteins. The highest binding affinity was recorded in fisetin-Bcl-xl protein complex (-8.8 kcal/mol). Meanwhile, the other flavonoids docked with Bcl-xl protein showed binding affinities, ranging from -8.0 to -8.6 kcal/mol. A total of four hydrogen bonds, four hydrophobic contacts, and one electrostatic interaction were detected in the docked fisetin-Bcl-xl complex, explaining its high binding affinity with Bcl-xl. The present results indicate that all flavonoids could potentially serve as Bcl-xl protein inhibitors, which would consequently lead to apoptotic process in ovarian cancers.
    Matched MeSH terms: Apoptosis; Apoptosis Regulatory Proteins
  18. In Vitro Cytotoxic Activity of Clinacanthus nutans Leaf Extracts Against HeLa Cells
    Haron NH, Md Toha Z, Abas R, Hamdan MR, Azman N, Khairuddean M, et al.
    Asian Pac J Cancer Prev, 2019 Feb 26;20(2):601-609.
    PMID: 30806066
    Objective: This study was conducted to investigate the antiproliferative activity of extracts of Clinacanthus nutans
    leaves against human cervical cancer (HeLa) cells. Methods: C. nutans leaves were subjected to extraction using 80%
    methanol or water. The methanol extract was further extracted to obtain hexane, dichloromethane (DCM), and aqueous
    fractions. The antiproliferative activity of the extracts against HeLa cells was determined. The most cytotoxic extract
    was furthered analyzed by apoptosis and cell cycle assays, and the phytochemical constituents were screened by gas
    chromatography-mass spectrometry (GC-MS). Results: All of the extracts were antiproliferative against HeLa cells, and
    the DCM fraction had the lowest IC50 value of 70 μg/mL at 48 h. Microscopic studies showed that HeLa cells exposed
    to the DCM fraction exhibited marked morphological features of apoptosis. The flow cytometry study also confirmed
    that the DCM fraction induced apoptosis in HeLa cells, with cell cycle arrest at the S phase. GC-MS analysis revealed
    the presence of at least 28 compounds in the DCM fraction, most of which were fatty acids. Conclusion: The DCM
    fraction obtained using the extraction method described herein had a lower IC50 value than those reported in previous
    studies that characterized the anticancer activity of C. nutans against HeLa cells.
    Matched MeSH terms: Apoptosis/drug effects*
  19. PNMA family: Protein interaction network and cell signalling pathways implicated in cancer and apoptosis
    Pang SW, Lahiri C, Poh CL, Tan KO
    Cell Signal, 2018 05;45:54-62.
    PMID: 29378289 DOI: 10.1016/j.cellsig.2018.01.022
    Paraneoplastic Ma Family (PNMA) comprises a growing number of family members which share relatively conserved protein sequences encoded by the human genome and is localized to several human chromosomes, including the X-chromosome. Based on sequence analysis, PNMA family members share sequence homology to the Gag protein of LTR retrotransposon, and several family members with aberrant protein expressions have been reported to be closely associated with the human Paraneoplastic Disorder (PND). In addition, gene mutations of specific members of PNMA family are known to be associated with human mental retardation or 3-M syndrome consisting of restrictive post-natal growth or dwarfism, and development of skeletal abnormalities. Other than sequence homology, the physiological function of many members in this family remains unclear. However, several members of this family have been characterized, including cell signalling events mediated by these proteins that are associated with apoptosis, and cancer in different cell types. Furthermore, while certain PNMA family members show restricted gene expression in the human brain and testis, other PNMA family members exhibit broader gene expression or preferential and selective protein interaction profiles, suggesting functional divergence within the family. Functional analysis of some members of this family have identified protein domains that are required for subcellular localization, protein-protein interactions, and cell signalling events which are the focus of this review paper.
    Matched MeSH terms: Apoptosis*
  20. Association between apoptotic neural tissue and cell proliferation in the adult teleost brain
    Lim FT, Ogawa S, Parhar IS
    Brain Res, 2016 11 01;1650:60-72.
    PMID: 27568467 DOI: 10.1016/j.brainres.2016.08.033
    Injury to neuronal tissues in the central nervous system (CNS) of mammals results in neural degeneration and sometime leads to loss of function, whereas fish retain a remarkable potential for neuro-regeneration throughout life. Thus, understanding the mechanism of neuro-regeneration in fish CNS would be useful to improve the poor neuro-regenerative capability in mammals. In the present study, we characterized a neuro-regenerative process in the brain of a cichlid, tilapia, Oreochromis niloticus. Morphological observations showed that the damaged brain region (habenula) successfully regrew and reinnervated axonal projections by 60 days post-damage. A fluorescent carbocyanine tracer, DiI tracing revealed a recovery of the major neuronal projection from the regenerated habenula to the interpenduncular nucleus by 60 days post-damage. TUNEL assay showed a significant increase of apoptotic cells (~234%, P<0.01) at one day post-damage, while the number of bromodeoxyuridine (BrdU)-positive proliferative cells were significantly increased (~92%, P<0.05) at 7 days post-damage compared with sham-control fish. To demonstrate a potential role of apoptotic activity in the neuro-regeneration, effects of degenerative neural tissue on cell proliferation were examined in vivo. Implantation of detached neural but not non-neural tissues into the cranial cavity significantly (P<0.01) increased the number of BrdU-positive cells nearby the implantation regions at 3 days after the implantation. Furthermore, local injection of the protein extract and cerebrospinal fluid collected from injured fish brain significantly induced cell proliferation in the brain. These results suggest that factor(s) derived from apoptotic neural cells may play a critical role in the neuro-regeneration in teleost brain.
    Matched MeSH terms: Apoptosis/physiology
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