Displaying publications 121 - 140 of 1101 in total

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  1. Fulltext The Role of MicroRNAs in Lung Cancer Metabolism
    Azizi MIHN, Othman I, Naidu R
    Cancers (Basel), 2021 Apr 05;13(7).
    PMID: 33916349 DOI: 10.3390/cancers13071716
    MicroRNAs (miRNAs) are short-strand non-coding RNAs that are responsible for post-transcriptional regulation of many biological processes. Their differential expression is important in supporting tumorigenesis by causing dysregulation in normal biological functions including cell proliferation, apoptosis, metastasis and invasion and cellular metabolism. Cellular metabolic processes are a tightly regulated mechanism. However, cancer cells have adapted features to circumvent these regulations, recognizing metabolic reprogramming as an important hallmark of cancer. The miRNA expression profile may differ between localized lung cancers, advanced lung cancers and solid tumors, which lead to a varying extent of metabolic deregulation. Emerging evidence has shown the relationship between the differential expression of miRNAs with lung cancer metabolic reprogramming in perpetuating tumorigenesis. This review provides an insight into the role of different miRNAs in lung cancer metabolic reprogramming by targeting key enzymes, transporter proteins or regulatory components alongside metabolic signaling pathways. These discussions would allow a deeper understanding of the importance of miRNAs in tumor progression therefore providing new avenues for diagnostic, therapeutic and disease management applications.
    Matched MeSH terms: Apoptosis
  2. Fulltext Apoptosis: Dual Role in Aetiology and Cure
    Wynn, Aye Aye, Myint, Ohnmar, Mya, Nang Khin
    Borneo Journal of Medical Sciences, 2019;13(3):5-10.
    MyJurnal
    Apoptosis is a programmed cell death which occurs following a variety of stimuli. Physiologically the process is important for morphogenesis of organs and homeostasis of different types of cells. Apoptotic cell death is responsible for a variety of pathologic states such as elimination of cell death in mutated cells, infected cells, tumour cells and transplant rejection well as the pathological atrophy. In this review, there is discussion about the control of apoptosis, detection methods of apoptosis, its association with infectious and non-communicable diseases. Intracellular microorganisms survive through inhibition of host cell apoptosis as well as they destroy the parenchymal cells causing impaired functions. It plays important role in tumourigenesis. There are possible therapeutic roles of drugs that modify apoptosis in human diseases.
    Matched MeSH terms: Apoptosis
  3. Fulltext Irigenin treatment alleviates doxorubicin (DOX)-induced cardiotoxicity by suppressing apoptosis, inflammation and oxidative stress via the increase of miR-425
    Guo L, Zheng X, Wang E, Jia X, Wang G, Wen J
    Biomed Pharmacother, 2020 May;125:109784.
    PMID: 32092815 DOI: 10.1016/j.biopha.2019.109784
    Doxorubicin (DOX) is an eff ;ective chemotherapeutic drug to suppress the progression of various types of tumors. However, its clinical application has been largely limited due to its potential cardiotoxicity. MicroRNAs (miRNAs) are emerged as critical regulators of cardiac injury. This study was aimed to explore the effects of irigenin (IR), as an isoflavonoid isolated from the rhizome of Belamcanda chinensis, on DOX-induced cardiotoxicity using the in vivo and in vitrostudies. The results indicated that DOX-induced fibrosis, cardiac dysfunction and injury were markedly attenuated by IR through reducing apoptosis, oxidative stress and inflammation in heart tissue samples. Importantly, DOX resulted in a remarkable decrease of miR-425 in heart tissues and cells, which was significantly rescued by IR. Receptor-interacting protein kinase 1 (RIPK1) was discovered to be a direct target of miR-425. DOX induced over-expression of RIPK1 both in vivo and in vitro, which were greatly decreased by IR. Transfection with miR-425 mimic could inhibit RIPK1 expression, whereas reducing miR-425 increased RIPK1 expression levels. In parallel to miR-425 over-expression, RIPK1 knockdown could attenuate apoptosis, reactive oxygen species (ROS) production and inflammation in HL-1 cells. However, over-expression of RIPK1 markedly abolished miR-425 mimic-induced apoptosis, ROS accumulation and inflammatory response in DOX-exposed cells. Herein, miR-425 could ameliorate cardiomyocyte injury through directly targeting RIPK1. Furthermore, activation of miR-425 by IR markedly improved DOX-induced cardiotoxicity, and therefore IR could be considered as a promising therapeutic agent for the treatment of cardiac injury.
    Matched MeSH terms: Apoptosis/drug effects; Apoptosis Regulatory Proteins/metabolism
  4. Stable W/O/W multiple nanoemulsion encapsulating natural tocotrienols and caffeic acid with cisplatin synergistically treated cancer cell lines (A549 and HEP G2) and reduced toxicity on normal cell line (HEK 293)
    Raviadaran R, Ng MH, Chandran D, Ooi KK, Manickam S
    Mater Sci Eng C Mater Biol Appl, 2021 Feb;121:111808.
    PMID: 33579452 DOI: 10.1016/j.msec.2020.111808
    This work aimed to evaluate the effects of encapsulated tocotrienols (TRF) and caffeic acid (CA) in water-in-oil-in-water (W/O/W) multiple nanoemulsion with cisplatin towards cancer cells. This work is important considering the limited efficacy of cisplatin due to tumour resistance, as well as its severe side effects. A549 and HEP G2 cancer cell lines were utilised for evaluating the efficacy of the encapsulated W/O/W while HEK 293 normal cell line was used for evaluating the toxicity. TRF, CA and CIS synergistically improved apoptosis in the late apoptotic phase in A549 and HEP G2 by 23.1% and 24.9%, respectively. The generation of ROS was enhanced using TRF:CA:CIS by 16.9% and 30.2% for A549 and HEP G2, respectively. Cell cycle analysis showed an enhanced cell arrest in the G0/G1 phase for both A549 and HEP G2. TRF, CA and CIS led to cell death in A549 and HEP G2. For HEK 293, ~33% cell viability was found when only CIS was used while >95% cell viability was observed when TRF, CA and CIS were used. This study demonstrates that the encapsulated TRF and CA in W/O/W with CIS synergistically improved therapeutic efficacy towards cancer cells, as well as lowered the toxicity effects towards normal cells.
    Matched MeSH terms: Apoptosis
  5. Fulltext Determination of time of death based on basic histological stain and immunostain changes
    Ezlan Elias, Khairul Osman, Sharifa Abdul Aziz, Abdul Halim Mansar, Siti Fatimah Ibrahim, Jamaludin Mohamed
    Jurnal Sains Kesihatan Malaysia, 2004;2(2):63-70.
    MyJurnal
    Establishing time of death has been extensively studied for the last 30 years. Parameters that have been studied included body temperature, biochemistry of rigor mortis, putrefactive changes and entomology. Despite an extensive study in these parameters it was found that all of the parameters were very much dependent on external factors like changes in surrounding temperature and activities done prior to death. To solve this problem, we decided to monitor the mechanism that occurs during death. Until now, various researches have found that during the early stage of death, heart and perfusion to the cells will stop. This will cause the cells to start the death process. The death of the cell will occurs either through apoptosis or necrosis. During apoptosis the cells will switch on and off a few proteins in a sequence. Based on this understanding, a study was conducted to determine if area ratio of apoptosis: necrosis and apoptotic p53 and Bcl-2 markers can be used as a reliable postmortem interval marker (PMI). Sampling of the study had involved 100 dead human skins with a known PMI. All samples were obtained from forensic unit of Hospital Kuala Lumpur (UFHKL). Ratio of apoptosis: necrosis areas were determined using hematoxilin and eosin staining while apoptosis p53 and Bcl-2 markers were done using an apoptosis kit. All staining were then indexed and plotted against PMI data obtained from UFHKL. Results indicated that there were no significant correlations between ratio of apoptosis: necrosis area against PMI (p = 0.144). Whereas for both apoptotic markers p53 and Bcl-2 PMI had shown a significant correlation (p < 0.000 for both results). In conclusion, we suggest that p53 and Bcl-2 parameters should be studied further since it is very likely that it could be a good indicator for PMI.
    Matched MeSH terms: Apoptosis
  6. Fulltext An introduction to DARC technology
    Ahmad SS
    Saudi J Ophthalmol, 2017 Jan-Mar;31(1):38-41.
    PMID: 28337061 DOI: 10.1016/j.sjopt.2016.08.001
    Glaucoma is a multi-factorial neurodegenerative disorder. The common denominator in all types of glaucomas is retinal ganglion cell death through apoptosis. However, this cellular demise in glaucoma is detected late by structural or functional analyses. There can be a 10-year delay prior to the appearance of visual field defects and pre-perimetric glaucoma is an issue still being addressed. However, a new cutting-edge technology called detection of apoptosing retinal cells (DARC) is being developed. This technique is capable of non-invasive, real-time visualization of apoptotic changes at the cellular level. It can detect glaucomatous cell damage at a very early stage, at the moment apoptosis starts, and thus management can be initiated even prior to development of visual field changes. In future, this technique will also be able to provide conclusive evidence of the effectiveness of treatment protocol and the need for any modifications which may be required. This article aims to provide a concise review of DARC technology.
    Matched MeSH terms: Apoptosis
  7. Phaleria macrocarpa (Boerl.) fruit induce G0/G1 and G2/M cell cycle arrest and apoptosis through mitochondria-mediated pathway in MDA-MB-231 human breast cancer cell
    Kavitha N, Ein Oon C, Chen Y, Kanwar JR, Sasidharan S
    J Ethnopharmacol, 2017 Apr 06;201:42-55.
    PMID: 28263848 DOI: 10.1016/j.jep.2017.02.041
    ETHNOPHARMACOLOGICAL RELEVANCE: Phaleria macrocarpa (Scheff) Boerl, is a well-known folk medicinal plant in Indonesia. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and hearth disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases.

    AIM OF THE STUDY: The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death.

    MATERIALS AND METHODS: MDA-MB-231 cells were incubated with PMEAF for 24h. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the Annexin V assay and also by fluorescence microscopy. Apoptosis protein profiling was detected by RayBio® Human Apoptosis Array.

    RESULTS: The AO/PI staining and flow cytometric analysis of MDA-MB-231 cells treated with PMEAF were showed apoptotic cell death. The cell cycle analysis by flow cytometry analysis revealed that the accumulation of PMEAF treated MDA-MB-231 cells in G0/G1 and G2/M-phase of the cell cycle. Moreover, the PMEAF exert cytotoxicity by increased the ROS production in MDA-MB-231 cells consistently stimulated the loss of mitochondrial membrane potential (∆Ψm) and induced apoptosis cell death by activation of numerous signalling proteins. The results from apoptosis protein profiling array evidenced that PMEAF stimulated the expression of 9 pro-apoptotic proteins (Bax, Bid, caspase 3, caspase 8, cytochrome c, p21, p27, p53 and SMAC) and suppressed the 4 anti-apoptotic proteins (Bcl-2, Bcl-w, XIAP and survivin) in MDA-MB-231 cells.

    CONCLUSION: The results indicated that PMEAF treatment induced apoptosis in MDA-MB-231 cells through intrinsic mitochondrial related pathway with the participation of pro and anti-apoptotic proteins, caspases, G0/G1 and G2/M-phases cell cycle arrest by p53-mediated mechanism.

    Matched MeSH terms: Apoptosis/drug effects; Apoptosis Regulatory Proteins/metabolism
  8. The in vitro and in vivo antitumor effects of Dracaena cinnabari resin extract on oral cancer
    Al-Afifi NA, Alabsi AM, Shaghayegh G, Ramanathan A, Ali R, Alkoshab M, et al.
    Arch Oral Biol, 2019 Aug;104:77-89.
    PMID: 31176147 DOI: 10.1016/j.archoralbio.2019.05.030
    OBJECTIVE: To study the potential for apoptosis induction of Dracaena cinnabari Balf. f methanolic extract (DCBME) on tongue squamous cell carcinoma cell line, H103. We evaluated the chemopreventive activity of DCBME against 4-nitroquinolone-1-oxide (4NQO)-induced tongue carcinogenesis in rat.

    DESIGN: Phase contrast microscope, acridine orange/propidium iodide (AO/PI) analysis of cells under fluorescence microscope, annexin-V flow-cytometry, DNA fragmentation, mitochondrial membrane potential, and caspase 3/7, 8 and 9 assays were performed. In vivo study, the rats were given 4NQO in their drinking water. The tongue was subjected to histopathological study to evaluate the incidence of squamous cell carcinoma (SCC).

    RESULTS: DCBME showed cytotoxic effect on H103 cells in a dose- and time-dependent manner. Furthermore, DCBME showed low cytotoxic effect on a normal cell line. In H103 cells, it caused cell morphology changes, S and G2/M-phase cell cycle arrest, significant reduction of cell migration and induced apoptosis through the intrinsic (mitochondrial) pathway. The incidence of SCC was 85.7% in the induced cancer and vehicle groups while in rats treated with DCBME at 100, 500 and 1000 mg/kg was 57.1%, 28.6% and 14.3%, respectively.

    CONCLUSIONS: (DCBME)-apoptosis induction reported in this work can be exploited as a potential antitumor agent with applications in medicinal treatments of tongue SCC.

    Matched MeSH terms: Apoptosis
  9. New developments and clinical transition of hyaluronic acid-based nanotherapeutics for treatment of cancer: reversing multidrug resistance, tumour-specific targetability and improved anticancer efficacy
    Safdar MH, Hussain Z, Abourehab MAS, Hasan H, Afzal S, Thu HE
    Artif Cells Nanomed Biotechnol, 2018 Dec;46(8):1967-1980.
    PMID: 29082766 DOI: 10.1080/21691401.2017.1397001
    This review aims to overview and critically analyses recent developments in achieving tumour-specific delivery of anticancer agents, maximizing anticancer efficacy, and mitigating tumour progression and off-target effects. Stemming from critical needs to develop target-specific delivery vehicles in cancer therapy, various hyaluronic acid (HA)-conjugated nanomedicines have been fabricated owing to their biocompatibility, safety, tumour-specific targetability of drugs and genes, and proficient interaction with cluster-determinant-44 (CD44) receptors over-expressed on the surface of tumour cells. HA-based conjugation or surface modulation of anticancer drugs encapsulated nanocarriers have shown promising efficacy against the various types of carcinomas of liver, breast, colorectal, pancreatic, lung, skin, ovarian, cervical, head and neck and gastric. The success of this emerging platform is assessed in achieving the rapid internalization of anticancer payloads into the tumour cells, impeding cancer cells division and proliferation, induction of cancer-specific apoptosis and prevention of metastasis (tumour progression). This review extends detailed insight into the engineering of HA-based nanomedicines, characterization, utilization for the diagnosis or treatment of CD44 over-expressing cancer subtypes and emphasizing the transition of nanomedicines to clinical cancer therapy.
    Matched MeSH terms: Apoptosis
  10. Fulltext A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease
    Haw TJ, Starkey MR, Nair PM, Pavlidis S, Liu G, Nguyen DH, et al.
    Mucosal Immunol, 2016 Jul;9(4):859-72.
    PMID: 26555706 DOI: 10.1038/mi.2015.111
    Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.
    Matched MeSH terms: Apoptosis; TNF-Related Apoptosis-Inducing Ligand/genetics; TNF-Related Apoptosis-Inducing Ligand/metabolism*
  11. Discovery of oxindole-based FLT3 inhibitors as a promising therapeutic lead for acute myeloid leukemia carrying the oncogenic ITD mutation
    Bender O, Shoman ME, Ali TFS, Dogan R, Celik I, Mollica A, et al.
    Arch Pharm (Weinheim), 2023 Feb;356(2):e2200407.
    PMID: 36403191 DOI: 10.1002/ardp.202200407
    FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation. Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48- and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells. The most potent compound 5a inhibited MV4-11 cells with IC50 of 4.3 µM at 72 h while it was 8.7 µM in THP-1 cells, thus showing two-fold selective inhibition against the oncogenic ITD mutation. The ability of 5a to modulate cell death was examined. High-throughput protein profiling revealed low levels of the growth factors IGFBP-2 and -4 with the blockage of various apoptotic inhibitors such as Survivin. p21 with cellular stress mechanisms was characterized by increased expression of HSP proteins along with TNF-β. Mechanistically, compounds 5a and 5b inhibited FLT3 kinase with IC50 values of 2.49 and 1.45 µM, respectively. Theoretical docking studies supported the compounds' ability to bind to the FLT3 ATP binding site with the formation of highly stable complexes as evidenced by molecular dynamics simulations. The designed compounds also provide suitable drug candidates with no violation of drug likeability rules.
    Matched MeSH terms: Apoptosis
  12. 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: Apoptosis
  13. Fulltext A Comprehensive Review of the Pharmacological Properties and Bioactive Components of Retama monosperma
    El Yadini A, Elouafy Y, Amiri-Ardekani E, Shafiee M, Firouzi A, Sasani N, et al.
    Molecules, 2023 Feb 10;28(4).
    PMID: 36838696 DOI: 10.3390/molecules28041708
    Retama monosperma L. (Boiss.) or Genista monosperma L. (Lam.), known locally as "R'tam", is a spontaneous and annual herb that belongs to the Fabaceae family. It is native to the Mediterranean regions, specifically in the desert areas and across the Middle Atlas in Morocco. This plant has been extensively used in folk medicine and it is rich in bioactive compounds, including polyphenols, flavonoids, and alkaloids. Current research efforts are focusing on the development of novel natural drugs as alternatives to various organic and non-organic chemical products from Retama monosperma. In addition, extract, and isolated compounds obtained from different parts of the chosen plant have been described to exhibit multiple biological and pharmacological properties such as antioxidant, anti-aging, anti-inflammatory, antihypertensive, anti-helminthic, disinfectant, diuretic, and hypoglycemic effects. The plant-derived extract also acts as an antimicrobial agent, which is highly efficient in the treatment of bacterial, viral, and fungal infections. Its antiproliferative effects are associated with some mechanisms, such as the inhibition of cell cycle arrest and apoptosis. In light of these assessments, we critically highlight the beneficial effects of the flowers, stems, seeds extracts, and isolated compounds from R. monosperma (L.) Boiss in human health care, industrial, and other applications, as well as the possible ways to be employed as a potential natural source for future drug discovery.
    Matched MeSH terms: Apoptosis
  14. Fulltext Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome
    Koike H, Harada M, Kusamoto A, Xu Z, Tanaka T, Sakaguchi N, et al.
    Front Endocrinol (Lausanne), 2023;14:1124405.
    PMID: 36875481 DOI: 10.3389/fendo.2023.1124405
    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic reticulum (ER) stress in the pathophysiology of PCOS. ER stress is defined as a condition in which unfolded or misfolded proteins accumulate in the ER because of an imbalance in the demand for protein folding and the protein-folding capacity of the ER. ER stress results in the activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which regulates various cellular activities. In principle, the UPR restores homeostasis and keeps the cell alive. However, if the ER stress cannot be resolved, it induces programmed cell death. ER stress has recently been recognized to play diverse roles in both physiological and pathological conditions of the ovary. In this review, we summarize current knowledge of the roles of ER stress in the pathogenesis of PCOS. ER stress pathways are activated in the ovaries of both a mouse model of PCOS and in humans, and local hyperandrogenism in the follicular microenvironment associated with PCOS is responsible for activating these. The activation of ER stress contributes to the pathophysiology of PCOS through multiple effects in granulosa cells. Finally, we discuss the potential for ER stress to serve as a novel therapeutic target for PCOS.
    Matched MeSH terms: Apoptosis
  15. Fulltext Molecular mechanisms underlying the clinical efficacy of panobinostat involve Stochasticity of epigenetic signaling, sensitization to anticancer drugs, and induction of cellular cell death related to cellular stresses
    El Omari N, Bakrim S, Khalid A, Abdalla AN, Almalki WH, Lee LH, et al.
    Biomed Pharmacother, 2023 Aug;164:114886.
    PMID: 37224752 DOI: 10.1016/j.biopha.2023.114886
    Panobinostat, also known as Farydak®, LBH589, PNB, or panobinostat lactate, is a hydroxamic acid that has been approved by the Food and Drug Administration (FDA) for its anti-cancer properties. This orally bioavailable drug is classified as a non-selective histone deacetylase inhibitor (pan-HDACi) that inhibits class I, II, and IV HDACs at nanomolar levels due to its significant histone modifications and epigenetic mechanisms. A mismatch between histone acetyltransferases (HATs) and HDACs can negatively affect the regulation of the genes concerned, which in turn can contribute to tumorigenesis. Indeed, panobinostat inhibits HDACs, potentially leading to acetylated histone accumulation, re-establishing normal gene expression in cancer cells, and helping to drive multiple signaling pathways. These pathways include induction of histone acetylation and cytotoxicity for the majority of tested cancer cell lines, increased levels of p21 cell cycle proteins, enhanced amounts of pro-apoptotic factors (such as caspase-3/7 activity and cleaved poly (ADP-ribose) polymerase (PARP)) associated with decreased levels of anti-apoptotic factors [B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra-large (Bcl-XL)], as well as regulation of immune response [upregulated programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression] and other events. The therapeutic outcome of panobinostat is therefore mediated by sub-pathways involving proteasome and/or aggresome degradation, endoplasmic reticulum, cell cycle arrest, promotion of extrinsic and intrinsic processes of apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this investigation, we aimed to pinpoint the precise molecular mechanism underlying panobinostat's HDAC inhibitory effect. A more thorough understanding of these mechanisms will greatly advance our knowledge of cancer cell aberrations and, as a result, provide an opportunity for the discovery of significant new therapeutic perspectives through cancer therapeutics.
    Matched MeSH terms: Apoptosis
  16. Kisspeptin-10 Mitigates α-Synuclein-Mediated Mitochondrial Apoptosis in SH-SY5Y-Derived Neurons via a Kisspeptin Receptor-Independent Manner
    Simon C, Soga T, Parhar I
    Int J Mol Sci, 2023 Mar 23;24(7).
    PMID: 37047030 DOI: 10.3390/ijms24076056
    The hypothalamic neurohormone kisspeptin-10 (KP-10) was inherently implicated in cholinergic pathologies when aberrant fluctuations of expression patterns and receptor densities were discerned in neurodegenerative micromilieus. That said, despite variable degrees of functional redundancy, KP-10, which is biologically governed by its cognate G-protein-coupled receptor, GPR54, attenuated the progressive demise of α-synuclein (α-syn)-rich cholinergic-like neurons. Under explicitly modeled environments, in silico algorithms further rationalized the surface complementarities between KP-10 and α-syn when KP-10 was unambiguously accommodated in the C-terminal binding pockets of α-syn. Indeed, the neuroprotective relevance of KP-10's binding mechanisms can be insinuated in the amelioration of α-syn-mediated neurotoxicity; yet it is obscure whether these extenuative circumstances are contingent upon prior GPR54 activation. Herein, choline acetyltransferase (ChAT)-positive SH-SY5Y neurons were engineered ad hoc to transiently overexpress human wild-type or E46K mutant α-syn while the mitigation of α-syn-induced neuronal death was ascertained via flow cytometric and immunocytochemical quantification. Recapitulating the specificity observed on cell viability, exogenously administered KP-10 (0.1 µM) substantially suppressed wild-type and E46K mutant α-syn-mediated apoptosis and mitochondrial depolarization in cholinergic differentiated neurons. In particular, co-administrations with a GPR54 antagonist, kisspeptin-234 (KP-234), failed to abrogate the robust neuroprotection elicited by KP-10, thereby signifying a GPR54 dispensable mechanism of action. Consistent with these observations, KP-10 treatment further diminished α-syn and ChAT immunoreactivity in neurons overexpressing wild-type and E46K mutant α-syn. Overall, these findings lend additional credence to the previous notion that KP-10's binding zone may harness efficacious moieties of neuroprotective intent.
    Matched MeSH terms: Apoptosis
  17. The regulation of Cytochrome f by mannose treatment in broccoli and its relationship with programmed cell death in tobacco BY-2 cells
    Zhao S, Chen J, Cao S, Wang H, Chen H, Wei Y, et al.
    Plant Physiol Biochem, 2024 Mar;208:108480.
    PMID: 38437751 DOI: 10.1016/j.plaphy.2024.108480
    It is well established that programmed cell death (PCD) occurred in broccoli during postharvest senescence, but no studies have been conducted on the regulation of broccoli cytochrome f by mannose treatment and its relationship with PCD. In this study, we treated broccoli buds with mannose to investigate the changes in color, total chlorophyll content, gene expression related to chlorophyll metabolism, chloroplast structure, and cytochrome f determination during postharvest storage. In addition, to investigate the effect of cytochrome f on PCD, we extracted cytochrome f from broccoli and treated Nicotiana tabacum L. cv Bright Yellow 2 (BY-2) cells with extracted cytochrome f from broccoli at various concentrations. The results showed that cytochrome f can induce PCD in tobacco BY-2 cells, as evidenced by altered cell morphology, nuclear chromatin disintegration, DNA degradation, decreased cell viability, and increased caspase-3-like protease production. Taken together, our study indicated that mannose could effectively delay senescence of postharvest broccoli by inhibiting the expression of gene encoding cytochrome f which could induce PCD.
    Matched MeSH terms: Apoptosis
  18. Dietary polystyrene nanoplastics exposure alters hepatic glycolipid metabolism, triggering inflammatory responses and apoptosis in Monopterus albus
    Zhu C, Zhou W, Han M, Yang Y, Li Y, Jiang Q, et al.
    Sci Total Environ, 2023 Sep 15;891:164460.
    PMID: 37247739 DOI: 10.1016/j.scitotenv.2023.164460
    Microplastics and nanoplastics (MPs and NPs) are abundant, persistent, and widespread environmental pollutants that are of increasing concern as they pose a serious threat to ecosystems and aquatic species. Identifying the ecological effects of NPs pollution requires understanding the effects of changing nanoplastics concentrations in aquatic organisms. Monopterus albus were orally fed three different concentrations of 100 nm polystyrene nanoplastics (PS-NPs): 0.05 %, 0.5 %, and 1 % of the feed for 28 days. Nanoplastics significantly activated the PPAR signaling pathway, Acyl-CoA oxidase 1 (ACOX1), carnitine palmitoyltransferase 1a (CPT1A), angiopoietin-like 4 (ANGPTL4), and phosphoenolpyruvate carboxykinase (PCK) at the mRNA level, resulting in disturbed lipid metabolism. Glutathione peroxidase (GSH-px) activity, catalase (CAT) activity, and malondialdehyde (MDA) were significantly elevated in the high nanoplastics-feeding exposure group, leading to oxidative stress in the liver. Overexpression of the cytokines genes Interleukin 1 (IL1B) and Interleukin-8 (IL8), Tumor necrosis factor alpha (TNF-α), activation of MAPK signaling pathway, and increased gene expression of c-Jun amino-terminal kinases (JNK) and p38 indicate that exposure to NPs may lead to hepatopancreas apoptosis through oxidative stress and inflammation. In summary, dietary PS-NPs exposure alters hepatic glycolipid metabolism, triggering inflammatory responses and apoptosis in M. albus. The results of this study provide valuable ecotoxicological data for a better understanding of the biological fate and effects of nanoplastics in M. albus.
    Matched MeSH terms: Apoptosis
  19. Fulltext Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications
    Kciuk M, Alam M, Ali N, Rashid S, Głowacka P, Sundaraj R, et al.
    Molecules, 2023 Jul 06;28(13).
    PMID: 37446908 DOI: 10.3390/molecules28135246
    Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited in the prevention and treatment of cancer. Epigallocatechin-3-gallate (EGCG) is the most abundant phenolic compound found in green tea. It has been shown to regulate multiple crucial cellular signaling pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, and others. Deregulation of the abovementioned pathways is involved in the pathophysiology of cancer. It has been demonstrated that EGCG may exert anti-proliferative, anti-inflammatory, and apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical and clinical studies suggest that EGCG may be used in the treatment of numerous disorders, including cancer. This review aims to summarize the existing knowledge regarding the biological properties of EGCG, especially in the context of cancer treatment and prophylaxis.
    Matched MeSH terms: Apoptosis
  20. Fulltext Transcriptomic Analysis of the Anticancer Effects of Annatto Tocotrienol, Delta-Tocotrienol and Gamma-Tocotrienol on Chondrosarcoma Cells
    Pang KL, Foong LC, Abd Ghafar N, Soelaiman IN, Law JX, Leong LM, et al.
    Nutrients, 2022 Oct 13;14(20).
    PMID: 36296960 DOI: 10.3390/nu14204277
    Previous studies have demonstrated the anticancer activities of tocotrienol on several types of cancer, but its effects on chondrosarcoma have never been investigated. Therefore, this study aims to determine the anticancer properties of annatto tocotrienol (AnTT), γ-tocotrienol (γ-T3) and δ-tocotrienol (δ-T3) on human chondrosarcoma SW1353 cells. Firstly, the MTT assay was performed to determine the half-maximal inhibitory concentration (IC50) of tocotrienol on SW1353 cells after 24 h treatment. The mode of cell death, cell cycle analysis and microscopic observation of tocotrienol-treated SW1353 cells were then conducted according to the respective IC50 values. Subsequently, RNAs were isolated from tocotrienol-treated cells and subjected to RNA sequencing and transcriptomic analysis. Differentially expressed genes were identified and then verified with a quantitative PCR. The current study demonstrated that AnTT, γ-T3 and δ-T3 induced G1 arrest on SW1353 cells in the early phase of treatment (24 h) which progressed to apoptosis upon 48 h of treatment. Furthermore, tocotrienol-treated SW1353 cells also demonstrated large cytoplasmic vacuolation. The subsequent transcriptomic analysis revealed upregulated signalling pathways in endoplasmic reticulum stress, unfolded protein response, autophagy and transcription upon tocotrienol treatment. In addition, several cell proliferation and cancer-related pathways, such as Hippo signalling pathway and Wnt signalling pathway were also significantly downregulated upon treatment. In conclusion, AnTT, γ-T3 and δ-T3 possess promising anticancer properties against chondrosarcoma cells and further study is required to confirm their effectiveness as adjuvant therapy for chondrosarcoma.
    Matched MeSH terms: Apoptosis
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