Displaying publications 721 - 740 of 1087 in total

Abstract:
Sort:
  1. Increased susceptibility of mice obtained from in vitro fertilization to global cerebral ischemia-reperfusion injury: possible role of hydrogen sulphide and its biosynthetic enzymes
    Li H, Liu L, Dang M, Zhang W, Liu J
    Int J Neurosci, 2020 Jun;130(6):533-540.
    PMID: 31516045 DOI: 10.1080/00207454.2019.1667797
    Aim of the Study: This study was designed to explore the relative susceptibility of in vitro fertilization (IVF)-conceived mice to global cerebral ischemic injury with the possible role of hydrogen sulphide and enzymes responsible for its production.Materials and Methods: IVF was carried to obtain pups, which were allowed to grow to the age of eight weeks. Thereafter, male mice were subjected to 20 min of global ischemia and 24 h of reperfusion. The mice obtained from other groups including normal mating, superovulation but normal mating and normal mating but embryo implantation were also subjected to global ischemia-reperfusion (I/R) injury.Results: IVF-derived mice exhibited significant more injury in response to I/R injury in comparison to other groups assessed in terms of impairment in locomotor activity, development of motor in coordination, neurological severity score, cerebral infarction and apoptosis markers (caspase-3 activity and Bcl-2 expression). Moreover, there was a relative decrease in the brain levels of hydrogen sulphide (H2S) and its biosynthetic enzymes viz. cystathionine-β-synthase and cystathionine-γ-lyase. Interestingly, the levels of H2S and cystathionine-γ-lyase were significantly low in IVF-derived mice in basal conditions also, i.e. before subjecting to I/R injury and these biochemical alterations were associated with the behavioural deficits in mice, even before subjecting to I/R injury.Conclusion: It is concluded that in vitro fertilization-derived mice are more susceptible to global cerebral I/R injury, which may be possibly due to decreased levels of hydrogen sulphide and its biosynthetic enzymes viz., cystathionine-β-synthase and cystathionine-γ-lyase.
    Matched MeSH terms: Apoptosis
  2. Fulltext Emerging Pathogenic and Prognostic Significance of Paired Box 3 (PAX3) Protein in Adult Gliomas
    Angelopoulou E, Paudel YN, Piperi C
    Transl Oncol, 2019 Jul 25;12(10):1357-1363.
    PMID: 31352198 DOI: 10.1016/j.tranon.2019.07.001
    Gliomas present the most common type of brain tumors in adults, characterized by high morbidity and mortality. In search of potential molecular targets, members of paired box (PAX) family have been found expressed in neural crest cells, regulating their proliferation, apoptosis, migration and differentiation. Recently, PAX3 overexpression has been implicated in glioma tumorigenesis by enhancing proliferation, increasing invasiveness and inducing resistance to apoptosis of glioma cells, while maintaining brain glioma stem cells (BGSCs) stemness. Although the oncogenic potential of PAX3 in gliomas is still under investigation, experimental evidence suggests that PAX3 function is mainly mediated through the canonical and non-canonical Wnt signaling pathway as well as through its interaction with GFAP and p53 proteins. In addition, PAX3 may contribute to the chemoresistance of glioma cells and modulates the effectiveness of novel experimental therapies. Further evidence indicates that PAX3 may represent a novel diagnostic and prognostic biomarker for gliomas, facilitating personalized treatment. This review addresses the emerging role of PAX3 in glioma diagnosis, prognosis and treatment, aiming to shed more light on the underlying molecular mechanisms that could lead to more effective treatment approaches.
    Matched MeSH terms: Apoptosis
  3. Molecular Modeling-Based Delivery System Enhances Everolimus-Induced Apoptosis in Caco-2 Cells
    Maki MAA, Kumar PV, Cheah SC, Siew Wei Y, Al-Nema M, Bayazeid O, et al.
    ACS Omega, 2019 May 31;4(5):8767-8777.
    PMID: 31459966 DOI: 10.1021/acsomega.9b00109
    Several studies have shown that the mammalian target of rapamycin (mTOR) inhibitor; everolimus (EV) improves patient survival in several types of cancer. However, the meaningful efficacy of EV as a single agent for the treatment of colorectal cancer (CRC) has failed to be proven in multiple clinical trials. Combination therapy is one of the options that could increase the efficacy and decrease the toxicity of the anticancer therapy. This study revealed that the β-cyclodextrin (β-CD):FGF7 complex has the potential to improve the antiproliferative effect of EV by preventing FGF receptor activation and by enhancing EV cellular uptake and intracellular retention. Molecular docking techniques were used to investigate the possible interaction between EV, β-CD, and FGF7. Molecular docking insights revealed that β-CD and EV are capable to form a stable inclusion complex with FGF at the molecular level. The aqueous solubility of the inclusion complex was increased (3.1 ± 0.23 μM) when compared to the aqueous solubility of pure EV (1.7 ± 0.16 μM). In addition, the in vitro cytotoxic activity of a FGF7:β-CD:EV complex on Caco-2 cell line was investigated using real-time xCELLigence technology. The FGF7:β-CD:EV complex has induced apoptosis of Caco-2 cells and shown higher cytotoxic activity than the parent drug EV. With the multitargets effect of β-CD:FGF7 and EV, the antiproliferative effect of EV was remarkably improved as the IC50 value of EV was reduced from 9.65 ± 1.42 to 1.87 ± 0.33 μM when compared to FGF7:β-CD:EV complex activity. In conclusion, the findings advance the understanding of the biological combinational effects of the β-CD:FGF7 complex and EV as an effective treatment to combat CRC.
    Matched MeSH terms: Apoptosis
  4. Synthesis, characterization and anti-cancer properties of water-soluble bis(PYE) pro-ligands and derived palladium(ii) complexes
    Zafar MN, Masood S, Chaudhry GE, Muhammad TST, Dalebrook AF, Nazar MF, et al.
    Dalton Trans, 2019 Aug 08.
    PMID: 31393494 DOI: 10.1039/c9dt01923e
    The two cationic palladium(ii) complexes, [Pd(Len)2][OTf]2 (4) and [Pd(Lphen)2][OTf]2 (5), were synthesized by treatment of bis(benzonitrile)dichloropalladium(ii) with [H2Len][OTf]2 (2) or [H2Lphen][OTf]2 (3), respectively, in the presence of a weak base. The pro-ligands 2 and 3 were synthesized by melt reactions between N-methyl-4-chloropyridinium triflate (1) and the amines ethylenediamine or phenylenediamine, respectively. The water-soluble compounds 2-5 were fully characterized, including by single-crystal X-ray crystal structure determinations for 2-4. UV-Vis and fluorescence spectroscopy were used to study the binding interactions of 2-5 with CT-DNA. The spectroscopic data suggested the presence of intercalative and groove binding modes and this was supported by molecular docking studies. The in vitro cytotoxicity studies (IC50 values) showed that the human breast cancer cell lines MCF-7 and T47D were more sensitive towards 3, 4 and 5 than cisplatin. The cytotoxicity of the new compounds decreased in the order 5 > 4 > 3 > 2. Furthermore, the annexin V-FITC staining method strongly suggested the presence of phosphatidylserine (PS) on the outer membrane of the treated cells, which is a hallmark of apoptosis.
    Matched MeSH terms: Apoptosis
  5. Pivotal Role of Fyn Kinase in Parkinson's Disease and Levodopa-Induced Dyskinesia: a Novel Therapeutic Target?
    Angelopoulou E, Paudel YN, Julian T, Shaikh MF, Piperi C
    Mol Neurobiol, 2021 Apr;58(4):1372-1391.
    PMID: 33175322 DOI: 10.1007/s12035-020-02201-z
    The exact etiology of Parkinson's disease (PD) remains obscure, although many cellular mechanisms including α-synuclein aggregation, oxidative damage, excessive neuroinflammation, and dopaminergic neuronal apoptosis are implicated in its pathogenesis. There is still no disease-modifying treatment for PD and the gold standard therapy, chronic use of levodopa is usually accompanied by severe side effects, mainly levodopa-induced dyskinesia (LID). Hence, the elucidation of the precise underlying molecular mechanisms is of paramount importance. Fyn is a tyrosine phospho-transferase of the Src family nonreceptor kinases that is highly implicated in immune regulation, cell proliferation and normal brain development. Accumulating preclinical evidence highlights the emerging role of Fyn in key aspects of PD and LID pathogenesis: it may regulate α-synuclein phosphorylation, oxidative stress-induced dopaminergic neuronal death, enhanced neuroinflammation and glutamate excitotoxicity by mediating key signaling pathways, such as BDNF/TrkB, PKCδ, MAPK, AMPK, NF-κB, Nrf2, and NMDAR axes. These findings suggest that therapeutic targeting of Fyn or Fyn-related pathways may represent a novel approach in PD treatment. Saracatinib, a nonselective Fyn inhibitor, has already been tested in clinical trials for Alzheimer's disease, and novel selective Fyn inhibitors are under investigation. In this comprehensive review, we discuss recent evidence on the role of Fyn in the pathogenesis of PD and LID and provide insights on additional Fyn-related molecular mechanisms to be explored in PD and LID pathology that could aid in the development of future Fyn-targeted therapeutic approaches.
    Matched MeSH terms: Apoptosis
  6. Fulltext Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes
    di Giacomo V, Chiavaroli A, Recinella L, Orlando G, Cataldi A, Rapino M, et al.
    Int J Mol Sci, 2020 05 18;21(10).
    PMID: 32443623 DOI: 10.3390/ijms21103575
    Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols. Although CBD's effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.
    Matched MeSH terms: Apoptosis
  7. Fulltext Increased fucoxanthin in Chaetoceros calcitrans extract exacerbates apoptosis in liver cancer cells via multiple targeted cellular pathways
    Foo SC, Yusoff FM, Imam MU, Foo JB, Ismail N, Azmi NH, et al.
    Biotechnol Rep (Amst), 2019 Mar;21:e00296.
    PMID: 30581767 DOI: 10.1016/j.btre.2018.e00296
    In this study, anti-proliferative effects of C. calcitrans extract and its fucoxanthin rich fraction (FxRF) were assessed on human liver HepG2 cancer cell line. Efficacy from each extract was determined by cytotoxicity assay, morphological observation, and cell cycle analysis. Mechanisms of action observed were evaluated using multiplex gene expression analysis. Results showed that CME and FxRF induced cytotoxicity to HepG2 cells in a dose and time-dependent manner. FxRF (IC50: 18.89 μg.mL-1) was found to be significantly more potent than CME (IC50: 87.5 μg.mL-1) (p 
    Matched MeSH terms: Apoptosis
  8. In Vivo Antitumor Activity of Folate-Conjugated Cholic Acid-Polyethylenimine Micelles for the Codelivery of Doxorubicin and siRNA to Colorectal Adenocarcinomas
    Amjad MW, Amin MC, Katas H, Butt AM, Kesharwani P, Iyer AK
    Mol Pharm, 2015 Dec 7;12(12):4247-58.
    PMID: 26567518 DOI: 10.1021/acs.molpharmaceut.5b00827
    Multidrug resistance poses a great challenge to cancer treatment. In order to improve the targeting and codelivery of small interfering RNA (siRNA) and doxorubicin, and to overcome multidrug resistance, we conjugated a cholic acid-polyethylenimine polymer with folic acid, forming CA-PEI-FA micelles. CA-PEI-FA exhibited a low critical micelle concentration (80 μM), small average particle size (150 nm), and positive zeta potential (+ 12 mV). They showed high entrapment efficiency for doxorubicin (61.2 ± 1.7%, w/w), forming D-CA-PEI-FA, and for siRNA, forming D-CA-PEI-FA-S. X-ray photoelectron spectroscopic analysis revealed the presence of external FA on D-CA-PEI-FA micelles. About 25% doxorubicin was released within 24 h at pH 7.4, while more than 30% release was observed at pH 5. The presence of FA enhanced micelle antitumor activity. The D-CA-PEI-FA and D-CA-PEI-FA-S micelles inhibited tumor growth in vivo. No significant differences between their in vitro cytotoxic activities or their in vivo antitumor effects were observed, indicating that the siRNA coloading did not significantly increase the antitumor activity. Histological analysis revealed that tumor tissues from mice treated with D-CA-PEI-FA or D-CA-PEI-FA-S showed the lowest cancer cell density and the highest levels of apoptosis and necrosis. Similarly, the livers of these mice exhibited the lowest level of dihydropyrimidine dehydrogenase among all treated groups. The lowest serum vascular endothelial growth factor level (VEGF) (24.4 pg/mL) was observed in mice treated with D-CA-PEI-FA-S micelles using siRNA targeting VEGF. These findings indicated that the developed CA-PEI-FA nanoconjugate has the potential to achieve targeted codelivery of drugs and siRNA.
    Matched MeSH terms: Apoptosis
  9. Nano-scaled materials may induce severe neurotoxicity upon chronic exposure to brain tissues: A critical appraisal and recent updates on predisposing factors, underlying mechanism, and future prospects
    Hussain Z, Thu HE, Elsayed I, Abourehab MAS, Khan S, Sohail M, et al.
    J Control Release, 2020 12 10;328:873-894.
    PMID: 33137366 DOI: 10.1016/j.jconrel.2020.10.053
    Owing to their tremendous potential, the inference of nano-scaled materials has revolutionized many fields including the medicine and health, particularly for development of various types of targeted drug delivery devices for early prognosis and successful treatment of various diseases, including the brain disorders. Owing to their unique characteristic features, a variety of nanomaterials (particularly, ultra-fine particles (UFPs) have shown tremendous success in achieving the prognostic and therapeutic goals for early prognosis and treatment of various brain maladies such as Alzheimer's disease, Parkinson's disease, brain lymphomas, and other ailments. However, serious attention is needful due to innumerable after-effects of the nanomaterials. Despite their immense contribution in optimizing the prognostic and therapeutic modalities, biological interaction of nanomaterials with various body tissues may produce severe nanotoxicity of different organs including the heart, liver, kidney, lungs, immune system, gastro-intestinal system, skin as well as nervous system. However, in this review, we have primarily focused on nanomaterials-induced neurotoxicity of the brain. Following their translocation into different regions of the brain, nanomaterials may induce neurotoxicity through multiple mechanisms including the oxidative stress, DNA damage, lysosomal dysfunction, inflammatory cascade, apoptosis, genotoxicity, and ultimately necrosis of neuronal cells. Our findings indicated that rigorous toxicological evaluations must be carried out prior to clinical translation of nanomaterials-based formulations to avoid serious neurotoxic complications, which may further lead to develop various neuro-degenerative disorders.
    Matched MeSH terms: Apoptosis
  10. Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway
    Saadatdoust Z, Pandurangan AK, Ananda Sadagopan SK, Mohd Esa N, Ismail A, Mustafa MR
    J Nutr Biochem, 2015 Dec;26(12):1547-58.
    PMID: 26355019 DOI: 10.1016/j.jnutbio.2015.07.024
    Patients with inflammatory bowel disease (IBD) are at increased risk for developing ulcerative colitis-associated colorectal cancer (CRC). The interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)-3 signaling regulates survival and proliferation of intestinal epithelial cells and play an important role in the pathogenesis of IBD and CRC. Cocoa is enriched with polyphenols that known to possess antioxidant, anti-inflammatory and antitumor activities. Here, we explored the antitumor effects and mechanisms of cocoa diet on colitis-associated cancer (CAC) using the azoxymethane/dextran sulfate sodium model, with a particular focus on whether cocoa exerts its anticancer effect through the IL-6/STAT3 pathway. We found that cocoa significantly decreased the tumor incidence and size in CAC-induced mice. In addition to inhibiting proliferation of tumor epithelial cells, cocoa suppressed colonic IL-6 expression and subsequently activation of STAT3. Thus, our findings demonstrated that cocoa diet suppresses CAC tumorigenesis, and its antitumor effect is partly mediated by limiting IL-6/STAT3 activation. In addition, cocoa induces apoptosis by increased the expressions of Bax and caspase 3 and decreased Bcl-xl. Thus, we conclude that cocoa may be a potential agent in the prevention and treatment of CAC.
    Matched MeSH terms: Apoptosis
  11. Immunohistochemical expression of Tazarotene-induced Gene 3 in oral squamous cell carcinoma
    Venkataswamy P, Samudrala Venkatesiah S, Rao RS, Banavar SR, Patil S, Augustine D, et al.
    J Oral Pathol Med, 2020 Dec 01.
    PMID: 33259689 DOI: 10.1111/jop.13144
    BACKGROUND: The prognosis of hyperproliferative skin lesions, such as psoriasis, basal cell carcinoma, and non-melanoma skin cancers, is significantly benefited from the levels of tazarotene-induced gene-1 (TIG3) expression and subsequent treatment with tazarotene. Such observations suggest that TIG3 could be used as a biomarker for apoptosis, differentiation, and proliferation. The current study aimed to evaluate the expression of TIG3 in normal oral mucosa (NOM) and oral squamous cell carcinoma (OSCC) compared with normal skin (NS) and skin squamous cell carcinoma (SSCC) using immunohistochemistry.

    METHODS: Seventeen cases each of SSCC, OSCC, NOM, and NS were evaluated. Each section was immunohistochemically stained with a rabbit polyclonal TIG3 antibody. The entire procedure was blinded and evaluated by 5 observers. Statistical analysis was performed using the chi-square test.

    RESULTS: There was a significant decrease in TIG3 protein expression in OSCC and SSCC compared with that in NOM and NS (P = 0.008). The progressive loss of expression was observed as the grade of both malignancies increased. However, there was no significant difference in the expression among the normal tissue groups and within SCC groups of similar grades.

    CONCLUSION: The present study suggests that the loss of TIG3 is an important event in carcinogenesis. TIG3 acts as a regulator of keratinocyte proliferation and terminal differentiation. Therefore, TIG3 could be a potential biomarker to differentiate aggressive and non-aggressive neoplasms.

    Matched MeSH terms: Apoptosis
  12. Fulltext Selective cytotoxicity effects of cytobiotics produced by lactic acid bacteria isolated from Malaysian foods
    Hooi Ling Foo
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):7-7.
    MyJurnal
    Probiotics are live microorganisms and when consumed in adequate amounts will confer health benefit on the host. Probiotic effects of Lactic Acid Bacteria (LAB) have been reported extensively, which rely generally on the viability of LAB cells. However, we have reported extensively the prominent probiotic effects of cell less postbiotics metabolites produced by various strains of Lactobacillus plantarum isolated from Malaysian foods on rats, poultry and pigs. L. plantarum is a major species of LAB. Despite the emerging evidence of anticancer properties of LAB, very limited information is available on the cytotoxic and antiproliferative activities of cytobiotic metabolites produced by LAB. Recently, we have documented the selective antiproliferative and cytotoxicity of cytobiotic produced by six strains of L. plantarum on normal human primary cells, breast, colorectal, cervical, liver and leukemia cancer cell lines via MTT assay, trypan blue exclusion method and BrdU assay. Haemolytic assay was used to determine the toxicity of cytobiotic using human and various animal red blood cells. The cytotoxicity mode was subsequently determined for selected UL4 cytobiotic on MCF-7 cells due to its pronounced cytotoxic effect by fluorescent microscopic ob-servation using AO/PI dye reagents and flow cytometric analyses. The selective cytotoxicity effect on various cancel cells that occurred in a strain-specific and cancer cell type-specific manner whilst sparing the normal cells will be discussed in the presentation. Moreover, the antiproliferative effects and induction of late apoptosis effects against selected malignant cancer cells will be discussed further in the presentation. This report reveals the vast potential of cytobiotics produced by L. plantarum strains as functional supplement and as an adjunctive treatment for cancer.
    Matched MeSH terms: Apoptosis
  13. Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index
    Abu N, Othman N, Ab Razak NS, Bakarurraini NAAR, Nasir SN, Soh JEC, et al.
    Front Cell Dev Biol, 2020;8:564648.
    PMID: 33324632 DOI: 10.3389/fcell.2020.564648
    Colorectal cancer (CRC) is one of the most widely diagnosed cancers worldwide. It has been shown that the body-mass index (BMI) of the patients could influence the tumor microenvironment, treatment response, and overall survival rates. Nevertheless, the mechanism on how BMI affects the tumorigenesis process, particularly the tumor microenvironment is still elusive. Herein, we postulate that extracellular vesicles (EVs) from CRC patients and non-CRC volunteers with different BMI could affect immune cells differently, in CD8 T cells particularly. We isolated the EVs from the archived serum of CRC patients with high and low BMI, as well as healthy controls with similar BMI status. The EVs were further characterized via electron microscopy, western blot and dynamic light scattering. Then, functional analysis was performed on CD8 T cells including apoptosis, cell proliferation, gene expression profiling and cytokine release upon co-incubation with the different EVs. Our results suggest that CRC-derived EVs were able to regulate the CD8 T cells. In some assays, low BMI EVs were functionally different than high BMI EVs. This study highlights the possible difference in the regulatory mechanism of cancer patients-derived EVs, especially on CD8 T cells.
    Matched MeSH terms: Apoptosis
  14. 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: Apoptosis
  15. Cytotoxic activity of phytochemicals from Garcinia mangostana L. and G. benthamiana (Planch. & Triana) Pipoly against breast cancer cells
    See I, Ee GCL, Jong VYM, Teh SS, Acuña CLC, Mah SH
    Nat Prod Res, 2020 Oct 23.
    PMID: 33094642 DOI: 10.1080/14786419.2020.1836629
    Four xanthones, α-mangostin (1), β-mangostin (2), mangostenol (3), mangaxanthone B (4), three benzophenones, mangaphenone (5), benthamianone (6), congestiflorone (7) and one sterol, stigmasterol (8) were isolated from the stem barks of Garcinia mangostana L. and G. benthamiana (Planch. & Triana) Pipoly. Compounds 1, 2, 4 and 5 exhibited significant cytotoxicity through MTT assay towards MCF-7 and MDA-MB-231 cells with the IC50 values range from 4.4 to 12.0 µM. Remarkably, mangaphenone (5) showed non-cytotoxicity against normal Vero cells, revealing its potential as lead compound for anti-breast cancer drug. Structure-activity relationship postulated that the prenyl and hydroxyl groups present in xanthones are important in promoting anti-proliferative effects. Molecular docking simulation study of 1, 2, 4 and 5 with 2OCF and 4PIV implied that the induction of apoptosis for both cancer cells involve ER and FAS signaling pathways. Future study on the lead optimization of 5 is highly recommended.
    Matched MeSH terms: Apoptosis
  16. Fulltext Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage
    Bakshi HA, Zoubi MSA, Hakkim FL, Aljabali AAA, Rabi FA, Hafiz AA, et al.
    Nutrients, 2020 06 26;12(6).
    PMID: 32604971 DOI: 10.3390/nu12061901
    Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
    Matched MeSH terms: Apoptosis
  17. Fulltext Heterometrus Spinifer: An Untapped Source of Anti-Tumor Molecules
    Soopramanien M, Khan NA, Ghimire A, Sagathevan K, Siddiqui R
    Biology (Basel), 2020 Jul 02;9(7).
    PMID: 32630812 DOI: 10.3390/biology9070150
    Despite intensive research, cancer incidence and mortality continue to rise. Consequently, the necessity to develop effective anti-cancer therapy is apparent. We have recently shown that the gut bacteria of animals living in polluted environments, such as crocodiles, are a potential source of novel anti-tumor molecules. To extend this work to other resilient species, we investigated the anti-tumor effects of gut bacteria of Heterometrus spinifer (a scorpion). Bacteria from the feces and gut were isolated, identified and evaluated for their anti-tumor effects. Bacterial-conditioned media was prepared in Roswell Park Memorial Institute (RPMI) 1640 media, and cytotoxicity and growth inhibitory properties were examined against cervical (HeLa) cancer cells. Liquid chromatography-mass spectrometry (LC-MS) was conducted to establish the identity of the molecules. Eighteen bacteria species from the gut (HSG01-18) and ten bacteria species from feces (HSF01-10) were tested for anti-tumor effects. Bacterial-conditioned media from scorpion gut and feces exhibited significant growth inhibitory effects against HeLa cells of 66.9% and 83.8%, respectively. Microscopic analysis of cancer cells treated with conditioned media HSG12 and HSG16 revealed apoptosis-like effects. HSG12 was identified as Pseudomonas aeruginosa and HSG16 was identified as Bacillus subtilis. Both conditioned media exhibited 100% growth inhibitory effects versus a selection of cancer cells, comprising cervical, breast and prostate cancer cells. LC-MS indicated the presence of 72 and 38 compounds, detected from HSG12 and HSG16, respectively. Out of these compounds, 47 were successfully identified while the remainder were unidentified and are possibly novel. This study suggests that the fecal and gut microbiota of scorpions might possess molecules with anti-cancer properties, however, further intensive research is needed to assess these expectations.
    Matched MeSH terms: Apoptosis
  18. Protective Effect of Natural Products against Huntington's Disease: An Overview of Scientific Evidence and Understanding Their Mechanism of Action
    Lum PT, Sekar M, Gan SH, Bonam SR, Shaikh MF
    ACS Chem Neurosci, 2021 Feb 03;12(3):391-418.
    PMID: 33475334 DOI: 10.1021/acschemneuro.0c00824
    Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of characteristic psychiatric disturbances and cognitive and motor dysfunction. To the best of our knowledge, there is no treatment available to completely mitigate the progression of HD. Among various therapeutic approaches, exhaustive literature reports have confirmed the medicinal benefits of natural products in HD experimental models. Building on this information, this review presents a brief overview of the neuroprotective mechanism(s) of natural products against in vitro/in vivo models of HD. Relevant studies were identified from several scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. After screening through literature from 2005 to the present, a total of 14 medicinal plant species and 30 naturally isolated compounds investigated against HD based on either in vitro or in vivo models were included in the present review. Behavioral outcomes in the HD in vivo model showed that natural compounds significantly attenuated 3-nitropropionic acid (3-NP) induced memory loss and motor incoordination. The biochemical alteration has been markedly alleviated with reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and increased mitochondrial energy production. Interestingly, following treatment with certain natural products, 3-NP-induced damage in the striatum was ameliorated, as seen histologically. Overall, natural products afforded varying degrees of neuroprotection in preclinical studies of HD via antioxidant and anti-inflammatory properties, preservation of mitochondrial function, inhibition of apoptosis, and induction of autophagy.
    Matched MeSH terms: Apoptosis
  19. Naturally occurring immunomodulators with antitumor activity: An insight on their mechanisms of action
    Mohamed SIA, Jantan I, Haque MA
    Int Immunopharmacol, 2017 Sep;50:291-304.
    PMID: 28734166 DOI: 10.1016/j.intimp.2017.07.010
    Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities. The anticancer activity of these immunomodulators is due to their anti-inflammatory, antioxidant, and induction of apoptosis, anti-angiogenesis, and anti-metastasis effect. These natural immunomodulators such as genistein, curcumin, and resveratrol can be used as prophylaxis against the initiation of cancer besides the inhibition of tumor growth and proliferation. Whereas, immunostimulants can elicit and activate humoral and cell-mediated immune responses against the tumor that facilitate the recognition and destruction of the already existing tumor. This review represents the recent studies on various natural immunomodulators with antitumor effects. We have focused on the relationship between their anticancer activity and immunomodulatory mechanisms. The mechanisms of action of various immunomodulators such as polyphenolic compounds, flavonoids, organosulfur compounds, capsaicin, vinca alkaloids, bromelain, betulinic acid and zerumbone, the affected cancerous cell lines in addition to the targeted molecules and transcriptional pathways have been review and critically analyzed.
    Matched MeSH terms: Apoptosis
  20. Fulltext Gallic acid induced apoptotic events in HCT-15 colon cancer cells
    Subramanian AP, Jaganathan SK, Mandal M, Supriyanto E, Muhamad II
    World J Gastroenterol, 2016 Apr 21;22(15):3952-61.
    PMID: 27099438 DOI: 10.3748/wjg.v22.i15.3952
    AIM: To investigate the inhibitory action of diet-derived phenolic compound gallic acid (GA) against HCT-15 colon cancer cells.
    METHODS: The antiproliferative effect of GA against colon cancer cells was determined by performing thiazolyl blue tetrazolium bromide (MTT) assay. The colony forming ability of GA treated colon cancer cells was evaluated using the colony forming assay. The cell cycle changes induced by GA in HCT-15 cells were analyzed by propidium iodide staining. Levels of reactive oxygen species (ROS) and mitochondrial membrane potential of HCT-15 exposed to GA was assessed using 2',7'-dichlorfluorescein-diacetate and rhodamine-123 respectively, with the help of flow cytometry. Morphological changes caused by GA treatment in the colon cancer cells were identified by scanning electron microscope and photomicrograph examination. Apoptosis was confirmed using flow cytometric analysis of GA treated HCT-15 cells after staining with Yo-Pro-1.
    RESULTS: MTT assay results illustrated that GA has an inhibitory effect on HCT-15 cells with IC50 value of 740 μmol/L. A time-dependent inhibition of colony formation was evident with GA treatment. Cell cycle arrest was evident from the accumulation of GA treated HCT-15 cells at sub-G1 phase (0.98 ± 1.03 vs 58.01 ± 2.05) with increasing exposure time. Flow cytometric analysis of GA treated HCT-15 cells depicted early events associated with apoptosis like lipid layer breakage and fall in mitochondrial membrane potential apart from an increase in the generation of ROS which were in a time dependent manner. SEM and photomicrograph images of the GA-treated cells displayed membrane blebbing and cell shrinking characteristics of apoptosis. Further apoptosis confirmation by Yo-Pro-1 staining also showed the time-dependent increase of apoptotic cells after treatment.
    CONCLUSION: These results show that GA induced ROS dependent apoptosis and inhibited the growth of colon cancer cells.
    KEYWORDS: Apoptosis; Cell cycle; Colon cancer; Gallic acid; Lipid layer break; Reactive oxygen species
    Matched MeSH terms: Apoptosis
Related Terms
Filters
Contact Us

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

External Links