Displaying publications 1 - 20 of 74 in total

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  1. siRNA Blocking of Mammalian Target of Rapamycin (mTOR) Attenuates Pathology in Annonacin-Induced Tauopathy in Mice
    Salama M, El-Desouky S, Alsayed A, El-Hussiny M, Magdy K, Fekry E, et al.
    Neurotox Res, 2019 May;35(4):987-992.
    PMID: 30362086 DOI: 10.1007/s12640-018-9974-3
    Tauopathy is a pathological hallmark of many neurodegenerative diseases. It is characterized by abnormal aggregates of pathological phosphotau and somatodendritic redistribution. One suggested strategy for treating tauopathy is to stimulate autophagy, hence, getting rid of these pathological protein aggregates. One key controller of autophagy is mTOR. Since stimulation of mTOR leads to inhibition of autophagy, inhibitors of mTOR will cause stimulation of autophagy process. In this report, tauopathy was induced in mice using annonacin. Blocking of mTOR was achieved through stereotaxic injection of siRNA against mTOR. The behavioral and immunohistochemical evaluation revealed the development of tauopathy model as proven by deterioration of behavioral performance in open field test and significant tau aggregates in annonacin-treated mice. Blocking of mTOR revealed significant clearance of tau aggregates in the injected side; however, tau expression was not affected by mTOR blockage.
    Matched MeSH terms: Autophagy
  2. [Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways]
    Fang QJ, Liu JJ, Wan YG, Liu BH, Tu Y, Wu W, et al.
    Zhongguo Zhong Yao Za Zhi, 2020 Dec;45(24):6003-6011.
    PMID: 33496141 DOI: 10.19540/j.cnki.cjcmm.20200709.401
    Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 μg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated β-galactosidase(SA-β-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.
    Matched MeSH terms: Autophagy*
  3. Fulltext Unveiling the dual role of autophagy in vascular remodelling and its related diseases
    Ren H, Dai R, Nik Nabil WN, Xi Z, Wang F, Xu H
    Biomed Pharmacother, 2023 Dec;168:115643.
    PMID: 37839111 DOI: 10.1016/j.biopha.2023.115643
    Vascular remodelling is an adaptive response to physiological and pathological stimuli that leads to structural and functional changes in the vascular intima, media, and adventitia. Pathological vascular remodelling is a hallmark feature of numerous vascular diseases, including atherosclerosis, hypertension, abdominal aortic aneurysm, pulmonary hypertension and preeclampsia. Autophagy is critical in maintaining cellular homeostasis, and its dysregulation has been implicated in the pathogenesis of various diseases, including vascular diseases. However, despite emerging evidence, the role of autophagy and its dual effects on vascular remodelling has garnered limited attention. Autophagy can exert protective and detrimental effects on the vascular intima, media and adventitia, thereby substantially influencing the course of vascular remodelling and its related vascular diseases. Currently, there has not been a review that thoroughly describes the regulation of autophagy in vascular remodelling and its impact on related diseases. Therefore, this review aimed to bridge this gap by focusing on the regulatory roles of autophagy in diseases related to vascular remodelling. This review also summarizes recent advancements in therapeutic agents targeting autophagy to regulate vascular remodelling. Additionally, this review offers an overview of recent breakthroughs in therapeutic agents targeting autophagy to regulate vascular remodelling. A deeper understanding of how autophagy orchestrates vascular remodelling can drive the development of targeted therapies for vascular diseases.
    Matched MeSH terms: Autophagy
  4. Umbilical Cord Mesenchymal Stem Cells Conditioned Medium Promotes Aβ25-35 phagocytosis by Modulating Autophagy and Aβ-Degrading Enzymes in BV2 Cells
    Xu Z, Nan W, Zhang X, Sun Y, Yang J, Lu K, et al.
    J Mol Neurosci, 2018 Jun;65(2):222-233.
    PMID: 29845511 DOI: 10.1007/s12031-018-1075-5
    Mesenchymal stem cell (MSC) therapy is a promising prospect for the treatment of Alzheimer's disease (AD); however, the underlying mechanisms by which MSCs mediate positive effects are still unclear. We speculated that MSCs mediate microglial autophagy and enhance the clearance of Aβ. To test this hypothesis, we cultured BV2 microglial cells with umbilical cord mesenchymal stem cells conditioned medium (ucMSCs-CM) in the presence or absence of Aβ25-35 oligomers. We investigated BV2 cell proliferation, cell death, and Aβ25-35 phagocytosis as well as protein expression levels of LC3, Beclin-1, p62, insulin-degrading enzyme (IDE), and neprilysin (Nep) with western blotting. The results showed that ucMSCs-CM inhibited the proliferation and decreased cell death of BV2 cells induced by Aβ25-35. ucMSCs-CM also promoted the phagocytosis of Aβ25-35 by BV2 cells and changed the expression of autophagy-related proteins LC3, Beclin-1, and p62. Treatment also upregulated the expression of Aβ-degrading enzymes IDE and Nep. Furthermore, the culture medium in BV2 cells with Aβ25-35 and ucMSCs-CM prevented neuronal cell SH-SY5Y from cell death compared to control medium without ucMSCs-CM. Altogether, these data suggested that ucMSCs-CM protect microglial and neuronal cells from Aβ25-35-induced cell death and promote Aβ phagocytosis by modulating autophagy and enhancing the expression of Aβ-degrading enzymes in microglia.
    Matched MeSH terms: Autophagy*
  5. Ultrastructural changes of cell morphology and viral morphogenesis of two ecotypes of dengue virus infection in human monocytic U-937 cell
    Fish-Low CY, Abu Bakar S, Othman F, Chee HY
    Trop Biomed, 2018 Dec 01;35(4):1154-1159.
    PMID: 33601863
    Dengue virus (DENV) is maintained and circulated in both sylvatic/enzootic and endemic/human cycles and spill over infection of sylvatic DENV into human populations has been reported. Extensive deforestation and increase human activities in forest may increase the risk of human exposure to sylvatic dengue infection and this may become a threat to human. Present study investigated the changes in cell morphology and viral morphogenesis upon infection with sylvatic and endemic ecotypes in human monocytic U-937 cells using transmission electron microscopy. Autophagy, a process that is either pro-viral or anti-viral, was observed in U-937 cells of both infections, however only the replication of endemic DENV was evidenced. An insight into the infection responses of sylvatic progenitors of DENV in susceptible host cells may provide better understanding on dengue emergence in human populations.
    Matched MeSH terms: Autophagy
  6. Fulltext Tocotrienols and oxidative stress in ocytes and developing embryos
    Yuhaniza Shafinie Kamsani, Mohd Hamim Rajikin
    Journal of Clinical and Health Sciences, 2017;2:8-18.
    This review summarizes the impact of tocotrienols (TCTs) as antioxidants in minimizing
    oxidative stress (OS), particularly in embryos exposed to OS causing agents. OS level is
    increased, for example, by nicotine, a major alkaloid content in cigarette, which is also a source
    of exogenous reactive oxygen species (ROS). Increased nicotine-induced OS increases cell
    stress response, which is a common trigger leading to embryonic cell death. Having more
    profound anti-oxidative stress effects than its counterpart tocopherol, TCTs improve blastocyst
    implantation, foetal growth, pregnancy outcome and survival of the neonates affected by
    nicotine. In reversing cell developmental arrest caused by nicotine-induced OS, TCTs enhances
    PDK-1 expression in the P13K/Akt pathway and permit embryonic development beyond the 4-
    cell stage with the production of more morulae. At the cytoskeletal level, TCTs increase the
    number of nicotine-induced apoptotic cells, through caspase 8 activation in the mitochondria.
    TCTs facilitate rough endoplasmic reticulum (rER) stress-mediated apoptosis and autophagy,
    resulting from nicotine-induced OS. Reduced vesicular population in TCT supplemented
    oocytes on the other hand may suggest reduced secretion of apoptotic cell bodies thus probably
    minimizing vesicular apoptosis during oocyte maturation. Further extensive research is
    required to develop TCTs as a tool in specific therapeutic approaches to overcome the
    detrimental effects of OS.
    Matched MeSH terms: Autophagy
  7. Fulltext Tocotrienols and oxidative stress in ocytes and developing embryos
    Yuhaniza Shafinie Kamsani, Mohd Hamim Rajikin
    Journal of Clinical and Health Sciences, 2017;2(2):8-18.
    MyJurnal
    This review summarizes the impact of tocotrienols (TCTs) as antioxidants in minimizing oxidative stress (OS), particularly in embryos exposed to OS causing agents. OS level is increased, for example, by nicotine, a major alkaloid content in cigarette, which is also a source of exogenous reactive oxygen species (ROS). Increased nicotine-induced OS increases cell stress response, which is a common trigger leading to embryonic cell death. Having more profound anti-oxidative stress effects than its counterpart tocopherol, TCTs improve blastocyst implantation, foetal growth, pregnancy outcome and survival of the neonates affected by nicotine. In reversing cell developmental arrest caused by nicotine-induced OS, TCTs enhances PDK-1 expression in the P13K/Akt pathway and permit embryonic development beyond the 4-cell stage with the production of more morulae. At the cytoskeletal level, TCTs increase the number of nicotine-induced apoptotic cells, through caspase 8 activation in the mitochondria. TCTs facilitate rough endoplasmic reticulum (rER) stress-mediated apoptosis and autophagy, resulting from nicotine-induced OS. Reduced vesicular population in TCT supplemented oocytes on the other hand may suggest reduced secretion of apoptotic cell bodies thus probably minimizing vesicular apoptosis during oocyte maturation. Further extensive research is required to develop TCTs as a tool in specific therapeutic approaches to overcome the detrimental effects of OS.
    Matched MeSH terms: Autophagy
  8. Fulltext Tocotrienols Modulate a Life or Death Decision in Cancers
    Tham SY, Loh HS, Mai CW, Fu JY
    Int J Mol Sci, 2019 Jan 16;20(2).
    PMID: 30654580 DOI: 10.3390/ijms20020372
    Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs.
    Matched MeSH terms: Autophagy/drug effects
  9. Fulltext The role of autophagy-related proteins in the pathogenesis of neuromyelitis optica spectrum disorders
    Guo HL, Shen XR, Liang XT, Li LZ
    Bioengineered, 2022 Jun;13(6):14329-14338.
    PMID: 36694421 DOI: 10.1080/21655979.2022.2084273
    This study aimed to investigate the expression of autophagy-related proteins in a mouse model of neuromyelitis optica (NMO). Mice were assigned to one of four groups: an animal experimental model group (NMO-EAE group, given with exogenous IL-17A), Interleukin-17 monoclonal antibody intervention group (NMO-EAE_0IL17inb), No exogenous interleukin-17 enhanced immune intervention group (NMO-EAE_0IL17), and a control group. Behavioral scores were assessed in each group, and the protein expressions of sequestosome 1 (P62), Beclin-1, the mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K-I), and LC3II/LC3I were detected using Western blotting. In the NMO-EAE_0IL17 group, the expression of Beclin-1 decreased, the LC3II/LC3I ratio was lower, and the expressions of P62, mTOR, and PI3K-I increased; after administration of IL-17A inhibitor into the brain tissue, however, the expression of Beclin-1 increased significantly, along with the LC3II/LC3I ratio, while the expressions of P62, mTOR and PI3K-I protein decreased significantly. In terms of behavioral scores, the scores of optic neuritis and myelitis were more serious, onset occurred earlier and the progress was faster, after the administration of IL-17A. In the mechanism of NMO animal model, IL-17A may regulate autophagy and affect the disease process through the activation of the PI3K-mTOR signaling pathway.
    Matched MeSH terms: Autophagy-Related Proteins
  10. The effects of polyphenols-rich tropical fruit juice on cognitive function and metabolomics profile - a randomized controlled trial in middle-aged women
    Rosli H, Shahar S, Rajab NF, Che Din N, Haron H
    Nutr Neurosci, 2021 Mar 05.
    PMID: 33666540 DOI: 10.1080/1028415X.2021.1880312
    Objectives: Polyphenols, particularly anthocyanins, have received attention in improving health issues during old age, including decline in cognitive function and other health parameters. We aimed to determine the effects of polyphenols-rich tropical fruit TP 3-in-1™ juice towards improving cognitive function, oxidative stress and metabolomics profiles among middle-aged women.Methods: This clinical trial involved 31 subjects with signs of poor cognitive function, as assessed using the Rey Auditory Verbal Learning Test (RAVLT). They were randomized to receive either TP 3-in-1™ juice (n = 16) or placebo (n = 15). Study subjects consumed 500 ml of beverages for three times per day, three days per week, for a period of ten weeks. Juice supplementation provided 9135 mg GAE of total phenolic content and 194.1 mg cyanidin-3-glucoside of total anthocyanin monomer.Results: There was a significant interaction effects on RAVLT immediate recall (p 
    Matched MeSH terms: Autophagy
  11. Fulltext The apoptotic effect of 1'S-1'-Acetoxychavicol Acetate (ACA) enhanced by inhibition of non-canonical autophagy in human non-small cell lung cancer cells
    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.
    Matched MeSH terms: Autophagy/drug effects*
  12. Fulltext The Osteoprotective Effects Of Kaempferol: The Evidence From In Vivo And In Vitro Studies
    Wong SK, Chin KY, Ima-Nirwana S
    Drug Des Devel Ther, 2019;13:3497-3514.
    PMID: 31631974 DOI: 10.2147/DDDT.S227738
    Kaempferol is a dietary bioflavonoid ubiquitously found in various types of plant. It possesses a wide range of medicinal properties suggesting its potential clinical utility that requires further investigation. The present review intends to highlight the efficacy of kaempferol and its molecular mechanisms of action in regulating bone metabolism. Many reports have acknowledged the bone-protecting property of kaempferol and kaempferol-containing plants using in vitro and in vivo experimental models. Kaempferol supplementation showed bone-sparing effects in newborn rats, glucocorticoid-induced and ovariectomy-induced osteoporotic models as well as bone fracture models. It achieves the bone-protective effects by inhibiting adipogenesis, inflammation, oxidative stress, osteoclastic autophagy and osteoblastic apoptosis while activating osteoblastic autophagy. The anti-osteoporotic effects of kaempferol are mediated through regulation of estrogen receptor, bone morphogenetic protein-2 (BMP-2), nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways. In summary, kaempferol exhibits beneficial effects on skeleton, thus is potentially effective for the prophylaxis and treatment of osteoporosis.
    Matched MeSH terms: Autophagy
  13. Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches
    Hashemi M, Nadafzadeh N, Imani MH, Rajabi R, Ziaolhagh S, Bayanzadeh SD, et al.
    Cell Commun Signal, 2023 Feb 09;21(1):32.
    PMID: 36759819 DOI: 10.1186/s12964-023-01053-z
    Autophagy is an evolutionarily conserved process that plays a role in regulating homeostasis under physiological conditions. However, dysregulation of autophagy is observed in the development of human diseases, especially cancer. Autophagy has reciprocal functions in cancer and may be responsible for either survival or death. Hepatocellular carcinoma (HCC) is one of the most lethal and common malignancies of the liver, and smoking, infection, and alcohol consumption can lead to its development. Genetic mutations and alterations in molecular processes can exacerbate the progression of HCC. The function of autophagy in HCC is controversial and may be both tumor suppressive and tumor promoting. Activation of autophagy may affect apoptosis in HCC and is a regulator of proliferation and glucose metabolism. Induction of autophagy may promote tumor metastasis via induction of EMT. In addition, autophagy is a regulator of stem cell formation in HCC, and pro-survival autophagy leads to cancer cell resistance to chemotherapy and radiotherapy. Targeting autophagy impairs growth and metastasis in HCC and improves tumor cell response to therapy. Of note, a large number of signaling pathways such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs regulate autophagy in HCC. Moreover, regulation of autophagy (induction or inhibition) by antitumor agents could be suggested for effective treatment of HCC. In this paper, we comprehensively review the role and mechanisms of autophagy in HCC and discuss the potential benefit of targeting this process in the treatment of the cancer. Video Abstract.
    Matched MeSH terms: Autophagy
  14. Fulltext Synthesis of gold nanoparticles with Solanum xanthocarpum extract and their in vitro anticancer potential on nasopharyngeal carcinoma cells
    Zhang P, Wang P, Yan L, Liu L
    Int J Nanomedicine, 2018;13:7047-7059.
    PMID: 30464458 DOI: 10.2147/IJN.S180138
    BACKGROUND: Nasopharyngeal cancer (NPC) is one of the subtypes of head and neck cancers. It occurs rarely, and its prevalence depends mainly on geographical location. Modern-day research is focused on coupling nanotechnology and traditional medicine for combating cancers. Gold nanoparticles (AuNPs) were synthesized from Solanum xanthocarpum (Sx) leaf extract using reduction method.

    METHODS: Characterization of the synthesized AuNPs was done by different techniques such as ultraviolet-visible spectrum absorption, X-ray diffraction, dynamic light scattering, Fourier transform infrared spectroscopy, transmission electron microscopy, and energy-dispersive X-ray analysis.

    RESULTS: All the results showed the successful green synthesis of AuNPs from Sx, which induced apoptosis of C666-1 cell line (NPC cell line). There was a decline in both cell viability and colony formation in C666-1 cells upon treatment with Sx-AuNPs. The cell death was proved to be caused by autophagy and mitochondrial-dependent apoptotic pathway.

    CONCLUSION: Thus, due to their anticancer potential, these nanoparticles coupled with Sx can be used for in vivo applications and clinical research in future.

    Matched MeSH terms: Autophagy/drug effects
  15. Fulltext Small Molecules Targeting Programmed Cell Death in Breast Cancer Cells
    Maniam S, Maniam S
    Int J Mol Sci, 2021 Sep 08;22(18).
    PMID: 34575883 DOI: 10.3390/ijms22189722
    Targeted chemotherapy has become the forefront for cancer treatment in recent years. The selective and specific features allow more effective treatment with reduced side effects. Most targeted therapies, which include small molecules, act on specific molecular targets that are altered in tumour cells, mainly in cancers such as breast, lung, colorectal, lymphoma and leukaemia. With the recent exponential progress in drug development, programmed cell death, which includes apoptosis and autophagy, has become a promising therapeutic target. The research in identifying effective small molecules that target compensatory mechanisms in tumour cells alleviates the emergence of drug resistance. Due to the heterogenous nature of breast cancer, various attempts were made to overcome chemoresistance. Amongst breast cancers, triple negative breast cancer (TNBC) is of particular interest due to its heterogeneous nature in response to chemotherapy. TNBC represents approximately 15% of all breast tumours, however, and still has a poor prognosis. Unlike other breast tumours, signature targets lack for TNBCs, causing high morbidity and mortality. This review highlights several small molecules with promising preclinical data that target autophagy and apoptosis to induce cell death in TNBC cells.
    Matched MeSH terms: Autophagy/drug effects; Autophagy/genetics
  16. Fulltext Simvastatin modulates cellular components in influenza A virus-infected cells
    Mehrbod P, Hair-Bejo M, Tengku Ibrahim TA, Omar AR, El Zowalaty M, Ajdari Z, et al.
    Int J Mol Med, 2014 Jul;34(1):61-73.
    PMID: 24788303 DOI: 10.3892/ijmm.2014.1761
    Influenza A virus is one of the most important health risks that lead to significant respiratory infections. Continuous antigenic changes and lack of promising vaccines are the reasons for the unsuccessful treatment of influenza. Statins are pleiotropic drugs that have recently served as anti-influenza agents due to their anti-inflammatory activity. In this study, the effect of simvastatin on influenza A-infected cells was investigated. Based on the MTT cytotoxicity test, hemagglutination (HA) assay and qPCR it was found that simvastatin maintained cell viability and decreased the viral load significantly as compared to virus-inoculated cells. The expression of important pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interferon-γ), which was quantified using ELISA showed that simvastatin decreased the expression of pro-inflammatory cytokines to an average of 2-fold. Furthermore, the modulation of actin filament polymerization was determined using rhodamine staining. Endocytosis and autophagy processes were examined by detecting Rab and RhoA GTPase protein prenylation and LC3 lipidation using western blotting. The results showed that inhibiting GTPase and LC3 membrane localization using simvastatin inhibits influenza replication. Findings of this study provide evidence that modulation of RhoA, Rabs and LC3 may be the underlying mechanisms for the inhibitory effects of simvastatin as an anti-influenza compound.
    Matched MeSH terms: Autophagy/drug effects
  17. Fulltext Saikosaponin A enhances Docetaxel efficacy by selectively inducing death of dormant prostate cancer cells through excessive autophagy
    Feng J, Xi Z, Jiang X, Li Y, Nik Nabil WN, Liu M, et al.
    Cancer Lett, 2023 Feb 01;554:216011.
    PMID: 36442771 DOI: 10.1016/j.canlet.2022.216011
    Quiescent cancer cells (QCCs), also known as dormant cancer cells, resist and survive chemo- and radiotherapy, resulting in treatment failure and later cancer recurrence when QCCs resume cell cycle progression. However, drugs selectively targeting QCCs are lacking. Saikosaponin A (SSA) derived from Bupleurum DC., is highly potent in eradicating multidrug-resistant prostate QCCs compared with proliferative prostate cancer cells. By further exacerbating the already increased autophagy through inactivation of Akt-mTOR signaling, SSA triggered cell death in QCCs. Contrarily, inhibition of autophagy or activation of Akt signaling pathway prevented SSA-induced cell death. The multicycle of Docetaxel treatments increased the proportion of QCCs, whereas administering SSA at intervals of Docetaxel treatments aggravated cell death in vitro and led to tumor growth arrest and cell death in vivo. In conclusion, SSA is posed as a novel QCCs-eradicating agent by aggravating autophagy in QCCs. In combination with the current therapy, SSA has potential to improve treatment effectiveness and to prevent cancer recurrence.
    Matched MeSH terms: Autophagy
  18. Fulltext Role of neurotoxicants in the pathogenesis of Alzheimer's disease: a mechanistic insight
    Nisa FY, Rahman MA, Hossen MA, Khan MF, Khan MAN, Majid M, et al.
    Ann Med, 2021 Dec;53(1):1476-1501.
    PMID: 34433343 DOI: 10.1080/07853890.2021.1966088
    Alzheimer's disease (AD) is the most conspicuous chronic neurodegenerative syndrome, which has become a significant challenge for the global healthcare system. Multiple studies have corroborated a clear association of neurotoxicants with AD pathogenicity, such as Amyloid beta (Aβ) proteins and neurofibrillary tangles (NFTs), signalling pathway modifications, cellular stress, cognitive dysfunctions, neuronal apoptosis, neuroinflammation, epigenetic modification, and so on. This review, therefore, aimed to address several essential mechanisms and signalling cascades, including Wnt (wingless and int.) signalling pathway, autophagy, mammalian target of rapamycin (mTOR), protein kinase C (PKC) signalling cascades, cellular redox status, energy metabolism, glutamatergic neurotransmissions, immune cell stimulations (e.g. microglia, astrocytes) as well as an amyloid precursor protein (APP), presenilin-1 (PSEN1), presenilin-2 (PSEN2) and other AD-related gene expressions that have been pretentious and modulated by the various neurotoxicants. This review concluded that neurotoxicants play a momentous role in developing AD through modulating various signalling cascades. Nevertheless, comprehension of this risk agent-induced neurotoxicity is far too little. More in-depth epidemiological and systematic investigations are needed to understand the potential mechanisms better to address these neurotoxicants and improve approaches to their risk exposure that aid in AD pathogenesis.Key messagesInevitable cascade mechanisms of how Alzheimer's Disease-related (AD-related) gene expressions are modulated by neurotoxicants have been discussed.Involvement of the neurotoxicants-induced pathways caused an extended risk of AD is explicited.Integration of cell culture, animals and population-based analysis on the clinical severity of AD is addressed.
    Matched MeSH terms: Autophagy
  19. Fulltext Regulation of autophagy by polyphenolic compounds as a potential therapeutic strategy for cancer
    Hasima N, Ozpolat B
    Cell Death Dis, 2014;5:e1509.
    PMID: 25375374 DOI: 10.1038/cddis.2014.467
    Autophagy, a lysosomal degradation pathway for cellular constituents and organelles, is an adaptive and essential process required for cellular homeostasis. Although autophagy functions as a survival mechanism in response to cellular stressors such as nutrient or growth factor deprivation, it can also lead to a non-apoptotic form of programmed cell death (PCD) called autophagy-induced cell death or autophagy-associated cell death (type II PCD). Current evidence suggests that cell death through autophagy can be induced as an alternative to apoptosis (type I PCD), with therapeutic purpose in cancer cells that are resistant to apoptosis. Thus, modulating autophagy is of great interest in cancer research and therapy. Natural polyphenolic compounds that are present in our diet, such as rottlerin, genistein, quercetin, curcumin, and resveratrol, can trigger type II PCD via various mechanisms through the canonical (Beclin-1 dependent) and non-canonical (Beclin-1 independent) routes of autophagy. The capacity of these compounds to provide a means of cancer cell death that enhances the effects of standard therapies should be taken into consideration for designing novel therapeutic strategies. This review focuses on the autophagy- and cell death-inducing effects of these polyphenolic compounds in cancer.
    Matched MeSH terms: Autophagy/drug effects; Autophagy/genetics
  20. Fulltext Regulation of autophagy by microRNAs in human breast cancer
    Chong ZX, Yeap SK, Ho WY
    J Biomed Sci, 2021 Mar 25;28(1):21.
    PMID: 33761957 DOI: 10.1186/s12929-021-00715-9
    Breast cancer is the most common solid cancer that affects female population globally. MicroRNAs (miRNAs) are short non-coding RNAs that can regulate post-transcriptional modification of multiple downstream genes. Autophagy is a conserved cellular catabolic activity that aims to provide nutrients and degrade un-usable macromolecules in mammalian cells. A number of in vitro, in vivo and clinical studies have reported that some miRNAs could modulate autophagy activity in human breast cancer cells, and these would influence human breast cancer progression and treatment response. Therefore, this review was aimed to discuss the roles of autophagy-regulating miRNAs in influencing breast cancer development and treatment response. The review would first introduce autophagy types and process, followed by the discussion of the roles of different miRNAs in modulating autophagy in human breast cancer, and to explore how would this miRNA-autophagy regulatory process affect the disease progression or treatment response. Lastly, the potential applications and challenges of utilizing autophagy-regulating miRNAs as breast cancer biomarkers and novel therapeutic agents would be discussed.
    Matched MeSH terms: Autophagy*
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