Displaying publications 1 - 20 of 82 in total

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  1. Kamarudin MN, Mohd Raflee NA, Hussein SS, Lo JY, Supriady H, Abdul Kadir H
    Drug Des Devel Ther, 2014;8:1765-80.
    PMID: 25336920 DOI: 10.2147/DDDT.S67980
    Alpha-lipoic acid, a potent antioxidant with multifarious pharmacological benefits has been reported to be neuroprotective in several neuronal models and used to treat neurological disorders such as Alzheimer's disease. Nonetheless, conclusive mechanisms of alpha-lipoic acid for its protective effects particularly in NG108-15 cells have never been investigated. In this study, the intricate neuroprotective molecular mechanisms by (R)-(+)-alpha-lipoic acid (R-LA) against H2O2-induced cell death in an in vitro model of neurodegeneration were elucidated. Pretreatment with R-LA (2 hours) significantly increased NG108-15 cell viability as compared to H2O2-treated cells and mitigated the induction of apoptosis as evidenced by Hoechst 33342/propidium iodide staining. R-LA (12.5-50 μM) aggrandized the reduced glutathione over glutathione disulfide ratio followed by a reduction in the intracellular reactive oxygen species level and an increase in mitochondrial membrane potential following H2O2 exposure. Moreover, pretreatment with R-LA stimulated the activation of PI3K-Akt through mTORC1 and mTORC2 components (mTOR, rictor and raptor) and production of antiinflammatory cytokine, IL-10 which led to the inactivation of glycogen synthase kinase-3β (GSK-3β) and reduction of both Bax/Bcl2 and Bax/Bcl-xL ratios, accompanied by inhibition of the cleaved caspase-3. Additionally, this observation was preceded by the suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α). The current findings accentuate new mechanistic insight of R-LA against apoptogenic and brain inflammatory factors in a neuronal model. These results further advocate the therapeutic potential of R-LA for the treatment of neurodegenerative diseases.
    Matched MeSH terms: Cell Death/drug effects
  2. Yew MY, Koh RY, Chye SM, Othman I, Ng KY
    PMID: 25308934 DOI: 10.1186/1472-6882-14-391
    Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the senile population with manifestation of motor disability and cognitive impairment. Reactive oxygen species (ROS) is implicated in the progression of oxidative stress-related apoptosis and cell death of the midbrain dopaminergic neurons. Its interplay with mitochondrial functionality constitutes an important aspect of neuronal survival in the perspective of PD. Edible bird's nest (EBN) is an animal-derived natural food product made of saliva secreted by swiftlets from the Aerodamus genus. It contains bioactive compounds which might confer neuroprotective effects to the neurons. Hence this study aims to investigate the neuroprotective effect of EBN extracts in the neurotoxin-induced in vitro PD model.
    Matched MeSH terms: Cell Death/drug effects
  3. Jamila N, Khairuddean M, Yaacob NS, Kamal NN, Osman H, Khan SN, et al.
    Bioorg Chem, 2014 Jun;54:60-7.
    PMID: 24813683 DOI: 10.1016/j.bioorg.2014.04.003
    Garcinia hombroniana (seashore mangosteen) in Malaysia is used to treat itching and as a protective medicine after child birth. This study was aimed to investigate the bioactive chemical constituents of the bark of G. hombroniana. Ethyl acetate and dichloromethane extracts of G. hombroniana yielded two new (1, 9) and thirteen known compounds which were characterized by the spectral techniques of NMR, UV, IR and EI/ESI-MS, and identified as; 2,3',4,5'-tetrahydroxy-6-methoxybenzophenone(1), 2,3',4,4'-tetrahydroxy-6-methoxybenzophenone (2), 2,3',4,6-tetrahydroxybenzophenone (3), 1,3,6,7-tetrahydroxyxanthone (4), 3,3',4',5,7-pentahydroxyflavone (5),3,3',5,5',7-pentahydroxyflavanone (6), 3,3',4',5,5',7-hexahydroxyflavone (7), 4',5,7-trihydroxyflavanone-7-rutinoside (8), 18(13→17)-abeo-3β-acetoxy-9α,13β-lanost-24E-en-26-oic acid (9), garcihombronane B (10), garcihombronane D (11), friedelan-3-one (12), lupeol (13), stigmasterol (14) and stigmasterol glucoside (15). In the in vitro cytotoxicity against MCF-7, DBTRG, U2OS and PC-3 cell lines, compounds 1 and 9 displayed good cytotoxic effects against DBTRG cancer cell lines. Compounds 1-8 were also found to possess significant antioxidant activities. Owing to these properties, this study can be further extended to explore more significant bioactive components of this plant.
    Matched MeSH terms: Cell Death/drug effects
  4. Khoo HE, Azlan A, Ismail A, Abas F, Hamid M
    PLoS One, 2014;9(1):e81447.
    PMID: 24416130 DOI: 10.1371/journal.pone.0081447
    Canarium odontophyllum, also known as CO, is a highly nutritious fruit. Defatted parts of CO fruit are potent sources of nutraceutical. This study aimed to determine oxidative stress and lipid peroxidation effects of defatted CO pericarp and peel extracts using in vitro bioassays. Cell cytotoxic effect of the CO pericarp and peel extracts were also evaluated using HUVEC and Chang liver cell lines. The crude extracts of defatted CO peel and pericarp showed cytoprotective effects in t-BHP and 40% methanol-induced cell death. The crude extracts also showed no toxic effect to Chang liver cell line. Using CD36 ELISA, NAD(+) and LDL inhibition assays, inhibition of oxidative stress were found higher in the crude extract of defatted CO peel compared to the pericarp extract. Hemoglobin and LDL oxidation assays revealed both crude extracts had significantly reduced lipid peroxidation as compared to control. TBARS values among defatted CO pericarp, peel, and cyanidin-3-glucoside showed no significant differences for hemoglobin and LDL oxidation assays. The protective effects of defatted CO parts, especially its peel is related to the presence of high anthocyanin that potentially offers as a pharmaceutical ingredient for cardioprotection.
    Matched MeSH terms: Cell Death/drug effects
  5. Hasan S, Al Ali H, Al-Qubaisi M, Zobir Hussein M, Ismail M, Zainal Z, et al.
    Int J Nanomedicine, 2012;7:3351-63.
    PMID: 22848164 DOI: 10.2147/IJN.S30809
    A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite "CETN," had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH) inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w). The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC₅₀ for CETN and ZLH are 617 and 670 μg/mL, respectively.
    Matched MeSH terms: Cell Death/drug effects
  6. Ramli NS, Eng Guan C, Nathan S, Vadivelu J
    PLoS One, 2012;7(9):e44104.
    PMID: 22970167 DOI: 10.1371/journal.pone.0044104
    Burkholderia pseudomallei, a Gram-negative saprophytic bacterium, is the causative agent of the potentially fatal melioidosis disease in humans. In this study, environmental parameters including temperature, nutrient content, pH and the presence of glucose were shown to play a role in in vitro biofilm formation by 28 B. pseudomallei clinical isolates, including four isolates with large colony variants (LCVs) and small colony variants (SCVs) morphotypes. Enhanced biofilm formation was observed when the isolates were tested in LB medium, at 30 °C, at pH 7.2, and in the presence of as little as 2 mM glucose respectively. It was also shown that all SVCs displayed significantly greater capacity to form biofilms than the corresponding LCVs when cultured in LB at 37 °C. In addition, octanoyl-homoserine lactone (C(8)-HSL), a quorum sensing molecule, was identified by mass spectrometry analysis in bacterial isolates referred to as LCV CTH, LCV VIT, SCV TOM, SCV CTH, 1 and 3, and the presence of other AHL's with higher masses; decanoyl-homoserine lactone (C(10)-HSL) and dodecanoyl-homoserine lactone (C(12)-HSL) were also found in all tested strain in this study. Last but not least, we had successfully acquired two Bacillus sp. soil isolates, termed KW and SA respectively, which possessed strong AHLs degradation activity. Biofilm formation of B. pseudomallei isolates was significantly decreased after treated with culture supernatants of KW and SA strains, demonstrating that AHLs may play a role in B. pseudomallei biofilm formation.
    Matched MeSH terms: Cell Death/drug effects
  7. Kalra J, Kumar P, Majeed AB, Prakash A
    Pharmacol. Biochem. Behav., 2016 Jul-Aug;146-147:1-12.
    PMID: 27106205 DOI: 10.1016/j.pbb.2016.04.002
    Several lines of evidence indicate that beta amyloid (β-A) production, neurofibrillary tangles and neuroinflammation are interrelated in the pathogenesis of Alzheimer's disease (AD). AD is associated with enhanced β-A production and accumulation resulting in neuroinflammation probably via activation of lipoxygenase (LOX) and cyclooxygenase (COX) pathways. Therefore, the present study was designed to investigate the role of LOX and COX inhibitors (zafirlukast and valdecoxib) in amyloidogenesis in β-A1-42 oligomer induced experimental AD in rats. The behavioral activities were assessed using actophotometer, novel object recognition test (ORT), Morris water maze (MWM) followed by biochemical assessments, determination of proinflammatory cytokines and mediators (TNF-α, IL-1β and PGE2), β-A1-42 levels and histopathological analysis. ICV administration of β-A1-42 oligomer produced significant impairment in memory consolidation. In addition to this significant increase in mito-oxidative stress, neuroinflammatory markers, acetylcholinesterase (AChE) toxicity, β-A1-42 level, neuronal cell death and neuroinflammation are more profound in β-A1-42 oligomer treated AD rats. Administration of zafirlukast (15 and 30mg/kg), and valdecoxib (5 and 10mg/kg) significantly improved the behavioral performances and showed significant reversal of mito-oxidative damage declining the neuroinflammation in β-A1-42 oligomer treated rats. Furthermore, more profound effects were observed at the sub-therapeutic dose combination of zafirlukast (15mg/kg) and valdecoxib (5mg/kg). The results of the present study indicate that protective effects of zafirlukast and valdecoxib are achieved through the blockade of release of LOX and COX metabolites therefore, representing a new therapeutic target for treating AD and other neurodegenerative disorders.
    Matched MeSH terms: Cell Death/drug effects
  8. Rati Selvaraju T, Khaza'ai H, Vidyadaran S, Sokhini Abd Mutalib M, Ramachandran V, Hamdan Y
    Int J Vitam Nutr Res, 2014;84(3-4):140-51.
    PMID: 26098478 DOI: 10.1024/0300-9831/a000201
    Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100-300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76% and 79% in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2%, 95.0%, and 95.6%, respectively (p<0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.
    Matched MeSH terms: Cell Death/drug effects*
  9. Sim SK, Tan YC, Tee JH, Yusoff AA, Abdullah JM
    Turk Neurosurg, 2015;25(4):617-24.
    PMID: 26242340 DOI: 10.5137/1019-5149.JTN.14035-15.1
    This study evaluated the neuroprotective effect of intrathecally infused paclitaxel in the prevention of motoneuron death and mitochondrial dysfunction following brachial plexus avulsion injury.
    Matched MeSH terms: Cell Death/drug effects
  10. Katouah H, Chen A, Othman I, Gieseg SP
    Int J Biochem Cell Biol, 2015 Oct;67:34-42.
    PMID: 26255116 DOI: 10.1016/j.biocel.2015.08.001
    Oxidised low density lipoprotein (oxLDL) is thought to be a significant contributor to the death of macrophage cells observed in advanced atherosclerotic plaques. Using human-derived U937 cells we have examined the effect of cytotoxic oxLDL on oxidative stress and cellular catabolism. Within 3h of the addition of oxLDL, there was a rapid, concentration dependent rise in cellular reactive oxygen species followed by the loss of cellular GSH, and the enzyme activity of both glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and aconitase. The loss of these catabolic enzymes was accompanied by the loss of cellular ATP and lower lactate generation. Addition of the macrophage antioxidant 7,8-dihydroneopterin inhibited the ROS generation, glutathione loss and catabolic inactivation. NOX was shown to be activated by oxLDL addition while apocynin inhibited the loss of GSH and cell viability. The data suggests that oxLDL triggers an excess of ROS production through NOX activation, and catabolic failure through thiol oxidation resulting in cell death.
    Matched MeSH terms: Cell Death/drug effects
  11. Lam KL, Yang KL, Sunderasan E, Ong MT
    Cell Prolif, 2012 Dec;45(6):577-85.
    PMID: 23046445 DOI: 10.1111/j.1365-2184.2012.00841.x
    OBJECTIVES: Latex from Hevea brasiliensis (natural rubber tree primarily cultivated for its rubber particles) has no known primary metabolic function, although its biological role is as a plant defence system. The present study has evaluated specific anti-proliferative effects of latex whole C-serum and its subfractions, on human cancer cell lines.

    MATERIALS AND METHODS: Cell viability assay using MTT, DNA fragmentation assay and real-time PCR were used to evaluate the cytotoxic effects of latex whole C-serum and its subfractions on the cell lines.

    RESULTS: MTT assay revealed very low LC(50) values, 2.0 and 280 ng/ml, for DCS and DCP treatments, respectively. DCS was proven to be more potent compared to DCP, in conferring specific anti-proliferative effects on the cancer cell lines. The study also indicated that anti-proliferative activity of pre-heated C-serum fractions diminished significantly.

    CONCLUSION: Although noteworthy cell death was reported, DNA fragmentation assay and real-time PCR confirmed that that induced by latex C-serum subfractions was not promoted via the classical apoptotic signalling pathway.

    Matched MeSH terms: Cell Death/drug effects
  12. Gurunanselage Don RAS, Yap MKK
    Biomed Pharmacother, 2019 Feb;110:918-929.
    PMID: 30572196 DOI: 10.1016/j.biopha.2018.12.023
    Arctium lappa L. is a perennial herb traditionally consumed to improve well-being. It has been widely reported for its antioxidant properties; however, very little is known for its exact mechanisms underlying the anticancer activity. This study aimed to investigate the mechanisms of anticancer action for different A. lappa root extracts. Arctium lappa root was extracted with ethanol, hexane and ethyl acetate, then examined for in vitro anticancer activity against cancerous HeLa, MCF-7, Jurkat cell lines and non-cancerous 3T3 cell lines. Induction of apoptosis was determined by cellular morphological changes, mitochondrial membrane potential (ΔΨm), caspase-3/7 activity and DNA fragmentation. The active compounds present in the most potent root extracts were identified by LC-ESI-MS. Among all the extracts, ethyl acetate root extract has the highest potency with IC50 of 102.2 ± 42.4 μg/ml, followed by ethanolic root extract in Jurkat T cells, at 24 h. None of the extracts were cytotoxic against 3T3 cells, suggesting that the extracts were selective against cancerous cells only. Both ethyl acetate and ethanolic root extracts exhibited significant morphological changes in Jurkat T cells, including the detachment from adjacent cells, appearance of apoptotic bodies and cells shrinkage. The extracts treated cells also displayed an increase in caspase-3/7 activity and alteration in mitochondrial membrane potential. Only ethyl acetate root extract at IC50 induced DNA fragmentation in Jurkat T cells. LC-ESI-MS analysis of the extract revealed the presence of 8 compounds, of which only 6 compounds with various biological activities reported. These findings suggest that the ethyl acetate extract of A. lappa had strong anticancer potential and induced intrinsic apoptosis via loss of ΔΨm and activation of caspase-3/7 This study can provide new insight to the discovery of new promising lead compound in chemopreventive and chemotherapeutic strategies.
    Matched MeSH terms: Cell Death/drug effects
  13. Subramani T, Yeap SK, Ho WY, Ho CL, Omar AR, Aziz SA, et al.
    J Cell Mol Med, 2014 Feb;18(2):305-13.
    PMID: 24266867 DOI: 10.1111/jcmm.12188
    Vitamin C is generally thought to enhance immunity and is widely taken as a supplement especially during cancer treatment. Tamoxifen (TAM) has both cytostatic and cytotoxic properties for breast cancer. TAM engaged mitochondrial oestrogen receptor beta in MCF-7 cells and induces apoptosis by activation of pro-caspase-8 followed by downstream events, including an increase in reactive oxygen species and the release of pro-apoptotic factors from the mitochondria. In addition to that, TAM binds with high affinity to the microsomal anti-oestrogen-binding site and inhibits cholesterol esterification at therapeutic doses. This study aimed to investigate the role of vitamin C in TAM-mediated apoptosis. Cells were loaded with vitamin C by exposure to dehydroascorbic acid, thereby circumventing in vitro artefacts associated with the poor transport and pro-oxidant effects of ascorbic acid. Pre-treatment with vitamin C caused a dose-dependent attenuation of cytotoxicity, as measured by acridine-orange/propidium iodide (AO/PI) and Annexin V assay after treatment with TAM. Vitamin C dose-dependently protected cancer cells against lipid peroxidation caused by TAM treatment. By real-time PCR analysis, an impressive increase in FasL and tumour necrosis factor-α (TNF-α) mRNA was detected after TAM treatment. In addition, a decrease in mitochondrial transmembrane potential was observed. These results support the hypothesis that vitamin C supplementation during cancer treatment may detrimentally affect therapeutic response.
    Matched MeSH terms: Cell Death/drug effects
  14. Navanesan S, Abdul Wahab N, Manickam S, Cheow YL, Sim KS
    Chem Biol Interact, 2017 Aug 01;273:37-47.
    PMID: 28578903 DOI: 10.1016/j.cbi.2017.05.022
    The active isolate of LF1 in Leptospermum javanicum was further looked into its capabilities in provoking an apoptotic reaction and suppressing the metastasis process in treated non-small lung cancer cells. LF1 underwent isolation and purification to yield a white powder which was identified as Betulinic acid (BA) via NMR, LCMS and IR spectroscopy. The isolate, BA, which produced an encouraging cytotoxic effect against non-small lung cancer cells (A549 and NCI-H1299) through the MTT assay, was further assessed with TUNEL, Sub-G1 population quantification, acridine orange/ethidium bromide staining as well as activated caspase-3 detection. The results pointed towards the induction of apoptosis as a result of increasing doses of BA, regardless of the p53 status in both cell lines. Treatment with BA also prevented an effective attachment of the invasive A549 cells onto a new culture surface in addition to diminishing the migratory potential of treated cells across a porous membrane. Further investigation through the ELISA detection and gelatin zymography showed an adverse effect to production of matrix metalloproteinase-2 (MMP-2) while the levels of matrix metalloproteinase-9 (MMP-9) were not negatively affected. The findings from this study validate the potential of L. javanicum as a potential anti-cancer treatment as stated in our previous study. The isolate, BA not only showed a capacity in inducing apoptotic cell death in non-small lung cancer cells, but managed to distort the ability of the cancer cells in effectively undergoing the metastasis process.
    Matched MeSH terms: Cell Death/drug effects
  15. Muchtaridi M, Yusuf M, Diantini A, Choi SB, Al-Najjar BO, Manurung JV, et al.
    Int J Mol Sci, 2014 Apr 25;15(5):7225-49.
    PMID: 24776765 DOI: 10.3390/ijms15057225
    Fevicordin-A (FevA) isolated from Phaleria macrocarpa (Scheff) Boerl. seeds was evaluated for its potential anticancer activity by in vitro and in silico approaches. Cytotoxicity studies indicated that FevA was selective against cell lines of human breast adenocarcinoma (MCF-7) with an IC50 value of 6.4 µM. At 11.2 µM, FevA resulted in 76.8% cell death of T-47D human breast cancer cell lines. Critical pharmacophore features amongst human Estrogen Receptor-α (hERα) antagonists were conserved in FevA with regard to a hypothesis that they could make notable contributions to its pharmacological activity. The binding stability as well as the dynamic behavior of FevA towards the hERα receptor in agonist and antagonist binding sites were probed using molecular dynamics (MD) simulation approach. Analysis of MD simulation suggested that the tail of FevA was accountable for the repulsion of the C-terminal of Helix-11 (H11) in both agonist and antagonist receptor forms. The flexibility of loop-534 indicated the ability to disrupt the hydrogen bond zipper network between H3 and H11 in hERα. In addition, MM/GBSA calculation from the molecular dynamic simulations also revealed a stronger binding affinity of FevA in antagonistic action as compared to that of agonistic action. Collectively, both the experimental and computational results indicated that FevA has potential as a candidate for an anticancer agent, which is worth promoting for further preclinical evaluation.
    Matched MeSH terms: Cell Death/drug effects
  16. Razali FN, Sinniah SK, Hussin H, Zainal Abidin N, Shuib AS
    Int J Biol Macromol, 2016 Nov;92:185-193.
    PMID: 27365117 DOI: 10.1016/j.ijbiomac.2016.06.079
    A polysaccharide fraction from Solanum nigrum, SN-ppF3 was shown previously to have an immunomodulatory activity where it could possibly be used to enhance the host immune response in fighting cancer. The non-toxic SN-ppF3 was fed orally to breast tumor bearing-mice with concentrations of 250 and 500mg/kg for 10days. During the treatment period, size of the tumor and weight of the mice were monitored. At the end of the treatment, blood, tumor, spleen and thymus were harvested for physiological and immunological analyses. After the treatment, the tumor volume and tumor weight were significantly inhibited by 65% and 40%, respectively. Based on the histological observation, the treatment of SN-ppF3 resulted in the disruption of tumor cells morphology. The increase in infiltrating T cells, NK cells and macrophages were observed in tumor tissues of the treated mice, which partly explained the higher apoptosis tumor cells observed in the treated mice. Moreover, the level of TNF-α, IFN-γ and IL-4 were elevated, while the level of IL-6 was decreased significantly, in serum of the treated mice. These results suggested that tumor suppression mechanisms observed in SN-ppF3-treated mice were most probably due through enhancing the host immune response.
    Matched MeSH terms: Cell Death/drug effects
  17. Subramaniam M, Liew SK, In L, Awang K, Ahmed N, Nagoor NH
    Drug Des Devel Ther, 2018;12:1053-1063.
    PMID: 29750018 DOI: 10.2147/DDDT.S141925
    Background: Drug combination therapy to treat cancer is a strategic approach to increase successful treatment rate. Optimizing combination regimens is vital to increase therapeutic efficacy with minimal side effects.

    Materials and methods: In the present study, we evaluated the in vitro cytotoxicity of double and triple combinations consisting of 1'S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP) and cisplatin (CDDP) against 14 various human cancer cell lines to address the need for more effective therapy. Our data show synergistic effects in MCF-7 cells treated with MIP:ACA, MIP:CDDP and MIP:ACA:CDDP combinations. The type of interaction between MIP, ACA and CDDP was evaluated based on combination index being <0.8 for synergistic effect. Identifying the mechanism of cell death based on previous studies involved intrinsic apoptosis and nuclear factor kappa B (NF-κB) and tested in Western blot analysis. Inactivation of NF-κB was confirmed by p65 and IκBα, while intrinsic apoptosis pathway activation was confirmed by caspase-9 and Apaf-1 expression.

    Results: All combinations confirmed intrinsic apoptosis activation and NF-κB inactivation.

    Conclusion: Double and triple combination regimens that target induction of the same death mechanism with reduced dosage of each drug could potentially be clinically beneficial in reducing dose-related toxicities.

    Matched MeSH terms: Cell Death/drug effects
  18. Nallappan D, Fauzi AN, Krishna BS, Kumar BP, Reddy AVK, Syed T, et al.
    Biomed Res Int, 2021;2021:5125681.
    PMID: 34631882 DOI: 10.1155/2021/5125681
    Studies on green biosynthesis of newly engineered nanoparticles for their prominent medicinal applications are being the torch-bearing concerns of the state-of-the-art research strategies. In this concern, we have engineered the biosynthesized Luffa acutangula silver nanoparticles of flavonoid O-glycosides in the anisotropic form isolated from aqueous leave extracts of Luffa acutangula, a popular traditional and ayurvedic plant in south-east Asian countries. These were structurally confirmed by Ultraviolet-visible (UV-Vis), Fourier transform infrared spectroscopy accessed with attenuated total reflection (FTIR-ATR) spectral analyses followed by the scanning electron microscopic (SEM) and the X-ray diffraction (XRD) crystallographic studies and found them with the face-centered cubic (fcc) structure. Medicinally, we have explored their significant antioxidant (DPPH and ABTS assays), antibacterial (disc diffusion assay on E. coli, S. aureus, B. subtilis, S. fecilis, and S. boydii), and anticancer (MTT assay on MCF-7, MDA-MB-231, U87, and DBTRG cell lines) potentialities which augmented the present investigation. The molecular docking analysis of title compounds against 3NM8 (DPPH) and 1DNU (ABTS) proteins for antioxidant activity; 5FGK (Gram-Positive Bacteria) and 1AB4 (Gram-Negative Bacteria) proteins for antibacterial activity; and 4GBD (MCF-7), 5FI2 (MDA-MB-231), 1D5R (U87), and 5TIJ (DBTRG) proteins for anticancer activity has affirmed the promising ligand-protein binding interactions among the hydroxy groups of the title compounds and aspartic acid of the concerned enzymatic proteins. The binding energy varying from -9.1645 to -7.7955 for Cosmosioside (1, Apigenin-7-glucoside) and from -9.2690 to -7.8306 for Cynaroside (2, Luteolin-7-glucoside) implies the isolated compounds as potential bioactive compounds. In addition, the performed studies like QSAR, ADMET, bioactivity properties, drug scores, and toxicity risks confirmed them as potential drug candidates and aspartic acid receptor antagonists. This research auxiliary augmented the existing array of phytological nanomedicines with new drug candidates that are credible with multiple bioactivities.
    Matched MeSH terms: Cell Death/drug effects
  19. Nalairndran G, Hassan Abdul Razack A, Mai CW, Fei-Lei Chung F, Chan KK, Hii LW, et al.
    J Cell Mol Med, 2020 Oct;24(20):12188-12198.
    PMID: 32926495 DOI: 10.1111/jcmm.15876
    Prostate cancer (PCa) is the most common malignancy and is the second leading cause of cancer among men globally. Using a kinome-wide lentiviral small-hairpin RNA (shRNA) library screen, we identified phosphoinositide-dependent kinase-1 (PDPK1) as a potential mediator of cell survival in PCa cells. We showed that knock-down of endogenous human PDPK1 induced significant tumour-specific cell death in PCa cells (DU145 and PC3) but not in the normal prostate epithelial cells (RWPE-1). Further analyses revealed that PDPK1 mediates cancer cell survival predominantly via activation of serum/glucocorticoid-regulated kinase 3 (SGK3). Knock-down of endogenous PDPK1 in DU145 and PC3 cells significantly reduced SGK3 phosphorylation while ectopic expression of a constitutively active SGK3 completely abrogated the apoptosis induced by PDPK1. In contrast, no such effect was observed in SGK1 and AKT phosphorylation following PDPK1 knock-down. Importantly, PDPK1 inhibitors (GSK2334470 and BX-795) significantly reduced tumour-specific cell growth and synergized docetaxel sensitivity in PCa cells. In summary, our results demonstrated that PDPK1 mediates PCa cells' survival through SGK3 signalling and suggest that inactivation of this PDPK1-SGK3 axis may potentially serve as a novel therapeutic intervention for future treatment of PCa.
    Matched MeSH terms: Cell Death/drug effects
  20. Selvaraju TR, Khaza'ai H, Vidyadaran S, Abd Mutalib MS, Vasudevan R
    Bosn J Basic Med Sci, 2014 Nov 16;14(4):195-204.
    PMID: 25428670 DOI: 10.17305/bjbms.2014.4.91
    Tocotrienol rich fraction (TRF) is an extract of palm oil, which consists of 25% alpha tocopherol (α-TCP) and 75% tocotrienols. TRF has been shown to possess potent antioxidant, anti-inflammatory, anticancer, neuroprotection, and cholesterol lowering activities. Glutamate is the main excitatory amino acid neurotransmitter in the central nervous system of mammalian, which can be excitotoxic, and it has been suggested to play a key role in neurodegenerative disorders like Parkinson's and Alzheimer's diseases. In this present study, the effects of vitamin E (TRF and α-TCP) in protecting astrocytes against glutamate injury were elucidated. Astrocytes induced with 180 mM of glutamate lead to significant cell death. However, glutamate mediated cytotoxicity was diminished via pre and post supplementation of TRF and α-TCP. Hence, vitamin E acted as a potent antioxidant agent in recovering mitochondrial injury due to elevated oxidative stress, and enhanced better survivability upon glutamate toxicity.
    Matched MeSH terms: Cell Death/drug effects
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