Displaying publications 81 - 100 of 584 in total

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  1. Mamidi MK, Pal R, Govindasamy V, Zakaria Z, Bhonde R
    Med Hypotheses, 2011 Apr;76(4):599-601.
    PMID: 21277690 DOI: 10.1016/j.mehy.2011.01.010
    The staggering number of publications featuring the use of stem cells has revolutionized regenerative medicine research. Preclinical studies indicate that allogeneic human mesenchymal stem cells (MSCs) may be useful for the treatment of several clinical disorders, including sepsis, acute renal failure, acute myocardial infarction, and more recently, acute lung injury (ALI). However, considerable success would not be obtained in clinical trials due to poor survival of transplanted cells under the influence of inflammatory conditions. Despite robust approaches like cellular reprogramming, scaffolds and conditioned media have been tested to overcome this problem; however the success rate of these approaches remain questionable. Recently, pretreatment of bioactive compounds in vitro have been shown to suppress cell apoptosis and promote cell survival. Quite likely a similar phenomenon can take place in vivo. Based on such studies, we hypothesize that MSCs derived from human post-natal tissues could be conditioned and prepared for targeted disease therapy. Depending on the disease condition, the MSCs could be treated prior to delivery with appropriate bioactive compounds to allow them survive longer and perform a better role as biocatalyst. The advantage of this approach could be the tailor made availability of MSCs preconditioned with appropriate bioactive compounds for disease specific therapy. Therefore, the choice of suitable bioactive molecule is likely to enhance the efficacy of targeted stem cell therapy and preconditioning may provide a novel strategy in maximizing biological and functional properties of MSCs.
    Matched MeSH terms: Cell Survival/drug effects
  2. Alkhader E, Roberts CJ, Rosli R, Yuen KH, Seow EK, Lee YZ, et al.
    J Biomater Sci Polym Ed, 2018 12;29(18):2281-2298.
    PMID: 30376409 DOI: 10.1080/09205063.2018.1541500
    Curcumin, the active ingredient of the rhizome curcuma longa has been extensively studied as an anticancer agent for various types of tumours. However, its efficacy as an anticancer agent is restricted due to poor absorption from the gastrointestinal tract, rapid metabolism and degradation in acidic medium. In the present study, we encapsulated curcumin in chitosan-pectinate nanoparticulate system (CUR-CS-PEC-NPs) for deployment of curcumin to the colon, whereby curcumin is protected against degradative effects in the upper digestive tract, and hence, maintaining its anticancer properties until colon arrival. The CUR-CS-PEC-NPs was taken up by HT-29 colorectal cancer cells which ultimately resulted in a significant reduction in cancer cell propagation. The anti-proliferative effect of the encapsulated curcumin was similar to that of free curcumin at equivalent doses which confirms that the encapsulation process did not impede the anticancer activity of curcumin. The oral bioavailability (Cmax, and AUC) of curcumin in CUR-CS-PEC-NPs was enhanced significantly by 4-folds after 6 hours of treatment compared to free curcumin. Furthermore, the clearance of curcumin from the CUR-CS-PEC-NPs was lower compared to free curcumin. These findings point to the potential application of the CUR-CS-PEC-NPs in the oral delivery of curcumin in the treatment of colon cancer.
    Matched MeSH terms: Cell Survival/drug effects
  3. Pillai MK, Young DJ, Bin Hj Abdul Majid HM
    Mini Rev Med Chem, 2018;18(14):1220-1232.
    PMID: 28969549 DOI: 10.2174/1389557517666171002154123
    The plant Alpinia officinarum of the ginger family originated in China and is used throughout South and South-East Asian countries to flavor food and as a traditional medicine to treat a variety of diseases. This review summarizes the biological, pharmacological and phytochemical properties of extracts and subsequently isolated compounds from A. officinarum. In vitro and in vivo studies of both extracts and pure compounds indicate a wide variety of potent bioactivities including antiinflammatory, antibacterial, antioxidant, antiobesity, anticancer, enzyme inhibitory and remarkable antiviral properties. The latter is particularly promising in the face of emerging, virulent respiratory diseases in Asia and the Middle East.
    Matched MeSH terms: Cell Survival/drug effects
  4. Ee GC, Lim CM, Lim CK, Rahmani M, Shaari K, Bong CF
    Nat Prod Res, 2009;23(15):1416-23.
    PMID: 19809914 DOI: 10.1080/14786410902757998
    Detailed chemical studies on the roots of Piper sarmentosum and Piper nigrum have resulted in several alkaloids. The roots of P. sarmentosum gave a new aromatic compound, 1-nitrosoimino-2,4,5-trimethoxybenzene (1). Piper nigrum roots gave pellitorine (2), (E)-1-[3',4'-(methylenedioxy)cinnamoyl]piperidine (3), 2,4-tetradecadienoic acid isobutyl amide (4), piperine (5), sylvamide (6), cepharadione A (7), piperolactam D (8) and paprazine (9). Structural elucidation of these compounds was achieved through NMR and MS techniques. Cytotoxic activity screening of the plant extracts indicated some activity.
    Matched MeSH terms: Cell Survival/drug effects
  5. Zare-Zardini H, Taheri-Kafrani A, Amiri A, Bordbar AK
    Sci Rep, 2018 01 12;8(1):586.
    PMID: 29330486 DOI: 10.1038/s41598-017-18938-y
    In this study, Rh2-treated graphene oxide (GO-Rh2), lysine-treated highly porous graphene (Gr-Lys), arginine-treated Gr (Gr-Arg), Rh2-treated Gr-Lys (Gr-Lys-Rh2) and Rh2-treated Gr-Arg (Gr-Arg-Rh2) were synthesized. MTT assay was used for evaluation of cytotoxicity of samples on ovarian cancer (OVCAR3), breast cancer (MDA-MB), Human melanoma (A375) and human mesenchymal stem cells (MSCs) cell lines. The percentage of apoptotic cells was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The hemolysis and blood coagulation activity of nanostructures were performed. Interestingly, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2 were more active against cancer cell lines in comparison with their cytotoxic activity against normal cell lines (MSCs) with IC50 values higher than 100 μg/ml. The results of TUNEL assay indicates a significant increase in the rates of TUNEL positive cells by increasing the concentrations of nanomaterials. Results were also shown that aggregation and changes of RBCs morphology were occurred in the presence of GO, GO-Rh2, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2. Note that all the samples had effect on blood coagulation system, especially on PTT. All nanostrucure act as antitumor drug so that binding of drugs to a nostructures is irresolvable and the whole structure enter to the cell as a drug.
    Matched MeSH terms: Cell Survival/drug effects
  6. Stone EL, Citossi F, Singh R, Kaur B, Gaskell M, Farmer PB, et al.
    Bioorg Med Chem, 2015 Nov 01;23(21):6891-9.
    PMID: 26474663 DOI: 10.1016/j.bmc.2015.09.052
    Potent, selective antitumour AhR ligands 5F 203 and GW 610 are bioactivated by CYPs 1A1 and 2W1. Herein we reason that DNA adducts' generation resulting in lethal DNA double strand breaks (DSBs) underlies benzothiazoles' activity. Treatment of sensitive carcinoma cell lines with GW 610 generated co-eluting DNA adducts (R(2)>0.7). Time-dependent appearance of γ-H2AX foci revealed subsequent DNA double strand breaks. Propensity for systemic toxicity of benzothiazoles steered development of prodrugs' hydrogels for localised delivery. Clinical applications of targeted therapies include prevention or treatment of recurrent disease after surgical resection of solid tumours. In vitro evaluation of 5F 203 prodrugs' activity demonstrated nanomolar potency against MCF-7 breast and IGROV-1 ovarian carcinoma cell lines.
    Matched MeSH terms: Cell Survival/drug effects
  7. Abdul Hamid Z, Lin Lin WH, Abdalla BJ, Bee Yuen O, Latif ES, Mohamed J, et al.
    ScientificWorldJournal, 2014;2014:258192.
    PMID: 25405216 DOI: 10.1155/2014/258192
    Hematopoietic stem cells- (HSCs-) based therapy requires ex vivo expansion of HSCs prior to therapeutic use. However, ex vivo culture was reported to promote excessive production of reactive oxygen species (ROS), exposing HSCs to oxidative damage. Efforts to overcome this limitation include the use of antioxidants. In this study, the role of Hibiscus sabdariffa L. (Roselle) in maintenance of cultured murine bone marrow-derived HSCs was investigated. Aqueous extract of Roselle was added at varying concentrations (0-1000 ng/mL) for 24 hours to the freshly isolated murine bone marrow cells (BMCs) cultures. Effects of Roselle on cell viability, reactive oxygen species (ROS) production, glutathione (GSH) level, superoxide dismutase (SOD) activity, and DNA damage were investigated. Roselle enhanced the survival (P < 0.05) of BMCs at 500 and 1000 ng/mL, increased survival of Sca-1(+) cells (HSCs) at 500 ng/mL, and maintained HSCs phenotype as shown from nonremarkable changes of surface marker antigen (Sca-1) expression in all experimental groups. Roselle increased (P < 0.05) the GSH level and SOD activity but the level of reactive oxygen species (ROS) was unaffected. Moreover, Roselle showed significant cellular genoprotective potency against H2O2-induced DNA damage. Conclusively, Roselle shows novel property as potential supplement and genoprotectant against oxidative damage to cultured HSCs.
    Matched MeSH terms: Cell Survival/drug effects
  8. Zha GF, Zhang CP, Qin HL, Jantan I, Sher M, Amjad MW, et al.
    Bioorg Med Chem, 2016 05 15;24(10):2352-9.
    PMID: 27083471 DOI: 10.1016/j.bmc.2016.04.015
    A series of new α,β-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aβ1-42 aggregation. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aβ1-42 aggregation. The compound 3o exhibited best AChE (IC50=0.037μM) inhibitory potential. Furthermore, compound 3o disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aβ aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aβ-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.
    Matched MeSH terms: Cell Survival/drug effects
  9. Khurshid Ahmed NA, Lim SK, Pandian GN, Sugiyama H, Lee CY, Khoo BY, et al.
    Mol Med Rep, 2020 Nov;22(5):3645-3658.
    PMID: 32901880 DOI: 10.3892/mmr.2020.11485
    Eurycoma (E.) longifolia Jack (Tongkat Ali) is a widely applied medicine that has been reported to boost serum testosterone and increase muscle mass. However, its actual biological targets and effects on an in vitro level remain poorly understood. Therefore, the present study aimed to investigate the effects of a standardised E. longifolia extract (F2) on the growth and its associated gene expression profile in mouse Leydig cells. F2, even at lower doses, was found to induce a high level of testosterone by ELISA. The level was as high as the levels induced by eurycomanone and formestane in Leydig cells. However, Leydig cells treated with F2 demonstrated reduced viability, which was likely due to the diminished cell population at the G0/G1 phase and increased cell population arrested at the S phase in the cell cycle, as assessed by MTT assay and flow cytometry, respectively. Cell viability was revived when the treatment time‑point was prolonged to 96 h. Genome‑wide gene analysis by reverse transcription‑quantitative PCR of F2‑treated Leydig cells at 72 h, when the cell growth was not revived, and 96 h, when the cell growth had started to revive, revealed cyclin‑dependent kinase‑like 2 (CDKL2) to be a potential target in regulating the viability of F2‑treated Leydig cells. Functional analysis, as analysed using GeneMANIA Cytoscape program v.3.6.0 (https://genemania.org/), further suggested that CDKL2 could act in concert with Casitas B‑lineage lymphoma and sphingosine kinase 1 interactor‑A‑kinase anchoring protein domain‑containing genes to regulate the viability of F2‑treated Leydig cells. The findings of the present study provide new insights regarding the potential molecular targets associated with the biological effect of E. longifolia extract on cell growth, particularly on the cell cycle, which could aid in enhancing the bioefficacy and reducing the toxicity of this natural product in the future.
    Matched MeSH terms: Cell Survival/drug effects
  10. Gul I, Yunus U, Ajmal M, Bhatti MH, Chaudhry GE
    Biomed Mater, 2021 Aug 31;16(5).
    PMID: 34375958 DOI: 10.1088/1748-605X/ac1c61
    Cancer is the leading cause of death worldwide. Capecitabine (CP) shows severe side effects because of early metabolism in stomach that affects the normal cells and organs, particularly liver and stomach. In this scope, we report the biocompatible, nontoxic polymeric thin films loaded with anti-cancer drug, CP for target specific, sublingual delivery of CP. Chitosan (CS) and polyvinyl alcohol (PVA) were used as biodegradable polymers alongwith glutaraldehyde (GLA) cross linker. CP-loaded thin films (TFCP1-TFCP5) were fabricated by solvent casting method. The results of Fourier transform infrared spectroscopy confirmed the presence of CP and polymers (CS and PVA) with GLA which binds through hydrogen bonding, and compatibility of drug with different excipients. Thermogravemetric analysis showed that the thin films are highly stable while differential scanning calorimeter thermograms confirmed the complete miscibility/entrapment of CP within PVA/CS thin film matrix. X-ray diffraction patterns revealed the molecular ineractions between CP and polymer matrix. High degree of swelling index of thin films at pH 7.4 was observed in comparison to pH 5.5. CP release studies in acetate (pH 5.5) and phosphate buffer (pH 7.4) showed that the thin films swell and result in drug diffusion faster in phosphate buffer through diffusion governed by Higuchi's model. Cytotoxicity results displayed that CPTFs killed MCF-7 and T47D (human breast adenocarcinoma) cells more effectively as compared to CP alone. The results of adhesion assay also showed that the PVA and CS both are safe and biocompatible. TFCP1 and TFCP3 thin films efficiently induced the apoptosis as compared to CP alone. The improved ability of TFCP1 and TFCP3 to induce cytotoxicity in MCF-7 cells reflects the potential of these thin films for targeted drug delivery. The CPTFs were stable for 4 months at 4 °C/60% ± 2%RH and 25 °C/70% ± 2%RH. In conclusion, the thin film formulations showed target specific controlled and burst release properties and thus could prove to be effective for human breast cancer treatment.
    Matched MeSH terms: Cell Survival/drug effects
  11. Wan Mohd Shukri WN, Bakhtiar H, Islam S, Bidin N, Baba S, Hamdan S, et al.
    Biomed Environ Sci, 2021 Feb 20;34(2):119-123.
    PMID: 33685570 DOI: 10.3967/bes2021.017
    Matched MeSH terms: Cell Survival/drug effects
  12. Mollataghi A, Hadi AH, Cheah SC
    Molecules, 2012 Apr 05;17(4):4197-208.
    PMID: 22481540 DOI: 10.3390/molecules17044197
    A new dienamide, (2E,4E)-7-(3',4'-dimethoxyphenyl)-N-ethyl-6-(R)-hydroxyhepta- 2,4-dienamide, named (-)-kunstleramide (1), were isolated from the bark of Beilschmiedia kunstleri Gamble together with one neolignan: (+)-kunstlerone (2) and seven known alkaloids: (+)-nornuciferine (3), (-)-isocaryachine (4), (+)-cassythicine (5), (+)-laurotetanine (6), (+)-boldine (7), noratherosperminine (8), (+)-N-demethylphyllocaryptine (9). Their structures were established from spectroscopic techniques, most notably 1D- and 2D-NMR, UV, IR, OR, circular dichroism (CD) spectra and LCMS-IT-TOF. (-)-Kunstleramide (1) exhibited very poor dose-dependent inhibition of DPPH activity, with an IC₅₀ value of 179.5 ± 4.4 μg/mL, but showed a moderate cytotoxic effect on MTT assays of A375, A549, HT-29, PC-3 and WRL-68 with EC₅₀ values of 64.65, 44.74, 55.94, 73.87 and 70.95 µg/mL, respectively.
    Matched MeSH terms: Cell Survival/drug effects
  13. Chan YY, Kim KH, Cheah SH
    J Ethnopharmacol, 2011 Oct 11;137(3):1183-8.
    PMID: 21810462 DOI: 10.1016/j.jep.2011.07.050
    ETHNOPHARMACOLOGICAL RELEVANCE: Sargassum polycystum, a type of brown seaweed, has been used for the treatment of skin-related disorders in traditional medicine.

    AIM OF THE STUDY: The aim of the present study is to investigate the antimelanogenesis effect of Sargassum polycystum extracts by cell-free mushroom tyrosinase assay followed by cell viability assay, cellular tyrosinase assay and melanin content assay using B16F10 murine melanoma cells.

    MATERIALS AND METHODS: Sargassum polycystum was extracted with 95% ethanol and further fractionated with hexane, ethyl acetate and water. The ethanolic crude extract and its fractionated extracts were tested for their potential to act as antimelanogenesis or skin-whitening agents by their abilities to inhibit tyrosinase activity in the cell-free mushroom tyrosinase assay and cellular tyrosinase derived from melanin-forming B16F10 murine melanoma cells. The tyrosinase inhibitory activity was correlated to the inhibition of melanin production in α-MSH-stimulated and unstimulated B16F10 cells.

    RESULTS: Sargassum polycystum ethanolic extract and its fractions had little or no inhibitory effect on mushroom tyrosinase activity. However, when tested on cellular tyrosinase, the ethanolic extract and its non-polar fraction, hexane fraction (SPHF), showed significant inhibition of cellular tyrosinase activity. In parallel to its cellular tyrosinase inhibitory activity, SPHF was also able to inhibit basal and α-MSH-stimulated melanin production in B16F10 cells.

    CONCLUSIONS: Our findings showed that (i) cellular tyrosinase assay is more reliable than mushroom tyrosinase assay in the initial testing of potential antimelanogenesis agents and, (ii) SPHF inhibited melanogenesis by inhibiting cellular tyrosinase activity. SPHF may be useful for treating hyperpigmentation and as a skin-whitening agent in cosmetics industry.

    Matched MeSH terms: Cell Survival/drug effects
  14. Chien SY, Hsu CH, Lin CC, Chuang YC, Lo YS, Hsi YT, et al.
    Environ Toxicol, 2017 Aug;32(8):2085-2092.
    PMID: 28383207 DOI: 10.1002/tox.22423
    Nasopharyngeal carcinoma (NPC), a tumor arising from epithelial cells that cover the surface and line the nasopharynx, is a rare malignancy worldwide but is prevalent in certain geographical areas, such as Southern Asia (Taiwan, Hong Kong, Singapore, Malaysia, and Southern China) and North Africa. Despite advances in diagnostic techniques and improvements in treatment modalities, the prognosis of NPC remains poor. Therefore, an effective chemotherapy regimen that enhances tumor sensitivity to chemotherapeutics is urgently required. Nimbolide, derived from Azadirachta indica, has a wide range of beneficial effects, including anti-inflammatory and anticancer properties. The present study evaluated the antitumor activity of nimbolide in NPC cells and its underlying mechanisms. Our results revealed that the treatment of HONE-1 cells with nimbolide potently inhibited cell viability. Moreover, nimbolide led to cell cycle arrest, which subsequently activated caspase-3, -8, and -9 and poly (ADP-ribose) polymerase to induce cell apoptosis. Moreover, nimbolide induced Bik, Bax, and t-Bid expression in HONE-1 cells. The results indicated that nimbolide induces apoptosis through the modulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways. Nimbolide induces apoptosis in human NPC cells and is a potential chemopreventive agent against NPC proliferation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2085-2092, 2017.
    Matched MeSH terms: Cell Survival/drug effects
  15. Li Y, Qin T, Ingle T, Yan J, He W, Yin JJ, et al.
    Arch Toxicol, 2017 Jan;91(1):509-519.
    PMID: 27180073 DOI: 10.1007/s00204-016-1730-y
    In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. A key question is whether the observed toxicity comes from the silver ions (Ag(+)) released from the AgNPs or from the nanoparticles themselves. In this study, we explored the genotoxicity and the genotoxicity mechanisms of Ag(+) and AgNPs. Human TK6 cells were treated with 5 nM AgNPs or silver nitrate (AgNO3) to evaluate their genotoxicity and induction of oxidative stress. AgNPs and AgNO3 induced cytotoxicity and genotoxicity in a similar range of concentrations (1.00-1.75 µg/ml) when evaluated using the micronucleus assay, and both induced oxidative stress by measuring the gene expression and reactive oxygen species in the treated cells. Addition of N-acetylcysteine (NAC, an Ag(+) chelator) to the treatments significantly decreased genotoxicity of Ag(+), but not AgNPs, while addition of Trolox (a free radical scavenger) to the treatment efficiently decreased the genotoxicity of both agents. In addition, the Ag(+) released from the highest concentration of AgNPs used for the treatment was measured. Only 0.5 % of the AgNPs were ionized in the culture medium and the released silver ions were neither cytotoxic nor genotoxic at this concentration. Further analysis using electron spin resonance demonstrated that AgNPs produced hydroxyl radicals directly, while AgNO3 did not. These results indicated that although both AgNPs and Ag(+) can cause genotoxicity via oxidative stress, the mechanisms are different, and the nanoparticles, but not the released ions, mainly contribute to the genotoxicity of AgNPs.
    Matched MeSH terms: Cell Survival/drug effects
  16. Bakhsheshi-Rad HR, Ismail AF, Aziz M, Akbari M, Hadisi Z, Khoshnava SM, et al.
    Mater Sci Eng C Mater Biol Appl, 2020 Jun;111:110812.
    PMID: 32279830 DOI: 10.1016/j.msec.2020.110812
    Magnesium (Mg) alloys present great potential for the development of orthopedic implants, whereas, their high degradation rate and poor antibacterial performance have restricted orthopedic applications. In this work, PLLA/GO-AgNP (poly-L-lactic acid/graphene oxide- silver nanoparticle) with different concentration of GO-AgNPs were deposited on Mg alloy via electrospinning method for enhancement of corrosion resistance and antibacterial performance. The result revealed that incorporation of GO into PLLA fibrous considerably slowed down the degradation rate of Mg alloy substrate and reduced the H2 release rate from the substrate. Also, co-incorporation of GO and AgNPs into PLLA fibrous resulted in substantial escalate in compressive strength after immersion in simulated body fluid (SBF). Antibacterial activity test exhibited that Mg alloy and neat PLLA fibrous presented minimal inhibition area toward Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In contrast, using PLLA/GO-AgNPs fibrous improved antibacterial performance against both bacteria. Cytocompatibility results indicated that PLLA/GO-AgNPs fibrous with a low amount of GO-AgNPs enhanced cell proliferation and growth while high co-incorporation of GO-AgNPs showed a negative effect on cell proliferation. Taken together, PLLA/1GO-AgNPs fibrous coating shows suitable corrosion resistance, cytocompatibility, and antibacterial function for use in orthopedic applications.
    Matched MeSH terms: Cell Survival/drug effects
  17. Zainal NS, Gan CP, Lau BF, Yee PS, Tiong KH, Abdul Rahman ZA, et al.
    Phytomedicine, 2018 Jan 15;39:33-41.
    PMID: 29433681 DOI: 10.1016/j.phymed.2017.12.011
    BACKGROUND: The CXCR4-RhoA and PI3K-mTOR signaling pathways play crucial roles in the dissemination and tumorigenesis of oral squamous cell carcinoma (OSCC). Activation of these pathways have made them promising molecular targets in the treatment of OSCC. Zerumbone, a bioactive monocyclic sesquiterpene isolated from the rhizomes of tropical ginger, Zingiber zerumbet (L.) Roscoe ex Sm. has displayed promising anticancer properties with the ability to modulate multiple molecular targets involved in carcinogenesis. While the anticancer activities of zerumbone have been well explored across different types of cancer, the molecular mechanism of action of zerumbone in OSCC remains largely unknown.

    PURPOSE: Here, we investigated whether OSCC cells were sensitive towards zerumbone treatment and further determined the molecular pathways involved in the mechanism of action.

    METHODS: Cytotoxicity, anti-proliferative, anti-migratory and anti-invasive effects of zerumbone were tested on a panel of OSCC cell lines. The mechanism of action of zerumbone was investigated by analysing the effects on the CXCR4-RhoA and PI3K-mTOR pathways by western blotting.

    RESULTS: Our panel of OSCC cells was broadly sensitive towards zerumbone with IC50 values of less than 5 µM whereas normal keratinocyte cells were less responsive with IC50 values of more than 25 µM. Representative OSCC cells revealed that zerumbone inhibited OSCC proliferation and induced cell cycle arrest and apoptosis. In addition, zerumbone treatment inhibited migration and invasion of OSCC cells, with concurrent suppression of endogenous CXCR4 protein expression in a time and dose-dependent manner. RhoA-pull down assay showed reduction in the expression of RhoA-GTP, suggesting the inactivation of RhoA by zerumbone. In association with this, zerumbone also inhibited the PI3K-mTOR pathway through the inactivation of Akt and S6 proteins.

    CONCLUSION: We provide evidence that zerumbone could inhibit the activation of CXCR4-RhoA and PI3K-mTOR signaling pathways leading to the reduced cell viability of OSCC cells. Our results suggest that zerumbone is a promising phytoagent for development of new therapeutics for OSCC treatment.

    Matched MeSH terms: Cell Survival/drug effects
  18. Wong RS, Radhakrishnan AK, Ibrahim TA, Cheong SK
    Microsc Microanal, 2012 Jun;18(3):462-9.
    PMID: 22640960 DOI: 10.1017/S1431927612000177
    Tocotrienols are isomers of the vitamin E family, which have been reported to exert cytotoxic effects in various cancer cells. Although there have been some reports on the effects of tocotrienols in leukemic cells, ultrastructural evidence of tocotrienol-induced apoptotic cell death in leukemic cells is lacking. The present study investigated the effects of three isomers of tocotrienols (alpha, delta, and gamma) on a human T lymphoblastic leukemic cell line (CEM-SS). Cell viability assays showed that all three isomers had cytotoxic effects (p < 0.05) on CEM-SS cells with delta-tocotrienol being the most potent. Transmission electron microscopy showed that the cytotoxic effects by delta- and gamma-tocotrienols were through the induction of an apoptotic pathway as demonstrated by the classical ultrastructural apoptotic changes characterized by peripheral nuclear chromatin condensation and nuclear fragmentation. These findings were confirmed biochemically by the demonstration of phosphatidylserine externalization via flow cytometry analysis. This is the first study showing classical ultrastructural apoptotic changes induced by delta- and gamma-tocotrienols in human T lymphoblastic leukemic cells.
    Matched MeSH terms: Cell Survival/drug effects
  19. Ganapathy R, Mani S, Hanumanth Rao BR, Tunku K, Ray B, Bhat A, et al.
    Front Biosci (Elite Ed), 2018 03 01;10:437-448.
    PMID: 29293467
    Thraatchathi Chooranam (TC), is a polyphenol-rich Indian traditional medicine. Present study was undertaken to investigate the effects of TC against H2O2 induced oxidative stress and apoptotic damage in H9C2 cardiomyocytes. Cell viability assay indicated relative safety (IC50= 488.10±12.04 mg/ml) of TC. Pretreatment of cells with TC upregulated anti-apoptotic Bcl2, and anti-oxidants TRX1 and TRXR and downregulated Bax and HIF-α and inflammatory genes iNOS and TNF-α. Together, these findings show that TC has both anti-oxidant and anti-apoptotic properties. Further studies may be considered to identify the bioactive principle(s) and precise mechanisms of action of TC.
    Matched MeSH terms: Cell Survival/drug effects
  20. Yap LV, Noor NM, Clyde MM, Chin HF
    Cryo Letters, 2011 May-Jun;32(3):188-96.
    PMID: 21766148
    The effects of sucrose preculture duration and loading treatment on tolerance of Garcinia cowa shoot tips to cryopreservation using the PVS2 vitrification solution were investigated. Ultrastructural changes in meristematic cells at the end of the preculture and loading steps were followed in an attempt to understand the effects of these treatments on structural changes in cell membranes and organelles. Increasing preculture duration on 0.3 M sucrose medium from 0 to 3 days enhanced tolerance to PVS2 solution from 5.6 percent (no preculture) to 49.2 percent (3-day preculture). However, no survival was observed after cryopreservation. Examination of meristematic cells by transmission electron microscopy revealed the progressive accumulation of an electron-dense substance in line with increasing exposure durations to 0.3 M sucrose preculture. Treatment with a loading solution (2 M glycerol + 0.4 M sucrose) decreased tolerance of shoot tips to PVS2 vitrification solution and had a deleterious effect on the ultrastructure of G. cowa meristematic cells. This study suggests that G. cowa meristematic cells may lose their structural integrity due to exposure to glycerol present in the loading solution at a 2 M concentration, either due to its high osmotic potential, or due to its cytotoxicity.
    Matched MeSH terms: Cell Survival/drug effects
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