Displaying publications 21 - 40 of 64 in total

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  1. Fulltext Cytotoxicity of targeted PLGA nanoparticles: a systematic review
    Chiu HI, Samad NA, Fang L, Lim V
    RSC Adv, 2021 Mar 01;11(16):9433-9449.
    PMID: 35423427 DOI: 10.1039/d1ra00074h
    Recent advances in nanotechnology have contributed tremendously to the development and revolutionizing of drug delivery systems in the field of nanomedicine. In particular, targeting nanoparticles based on biodegradable poly(lactic-co-glycolic acid) (PLGA) polymers have gained much interest. However, PLGA nanoparticles remain of concern for their effectiveness against cancer cells and their toxicity to normal cells. The aim of this systematic review is to identify a promising targeting PLGA nanoformulation based on the comparison study of their cytotoxicity potency in different cell lines. A literature search was conducted through the databases of Google Scholar, PubMed, ScienceDirect, Scopus and SpringerLink. The sources studied were published between 2009 and 2019, and a variety of keywords were utilized. In total, 81 manuscripts that met the inclusion and exclusion criteria were selected for analysis based on their cytotoxicity, size, zeta potential, year of publication, type of ligand, active compounds and cell line used. The half maximal inhibitory concentration (IC50) for cytotoxicity was the main measurement in this data extraction, and the SI units were standardized to μg mL-1 for a better view of comparison. This systematic review also identified that cytotoxicity potency was inversely proportional to nanoparticle size. The PLGA nanoparticles predominantly exhibited a size of less than 300 nm and absolute zeta potential ∼20 mV. In conclusion, more comprehensive and critical appraisals of pharmacokinetic, pharmacokinetic, toxicokinetic, in vivo and in vitro tests are required for the investigation of the full value of targeting PLGA nanoparticles for cancer treatment.
  2. Fulltext Editorial: Recent advances in small molecule-based targeted therapy for breast cancer
    Htar TT, Naidu R, Lim V, Pandey AK
    Front Pharmacol, 2023;14:1343664.
    PMID: 38192413 DOI: 10.3389/fphar.2023.1343664
  3. Clinacanthus nutans crude polysaccharide extract as a green platform for microwave-assisted synthesis of silver nanoparticles: Optimization, characterization, and evaluation of bioactivities
    Devasvaran K, Alallam B, Lee C, Yong YK, Lim V
    Int J Biol Macromol, 2024 Aug 19.
    PMID: 39168213 DOI: 10.1016/j.ijbiomac.2024.134893
    Clinacanthus nutans (C. nutans) is a plant in tropical Asia with proven biological activities. The optimized extraction method of C. nutans crude polysaccharide (CNP) uses water in the presence of an ultrasound-assisted mechanical method (UL_CNP). However, the use of UL_CNP for the synthesis and optimization of silver nanoparticles (AgNP), particularly their anticancer and photocatalytic properties, remains unexplored. Hence, this research aimed to employ a green method using UL_CNP and silver nitrate to produce AgNP (UL_AgNP) with a small size and assess its potential toxicity, anticancer, and photocatalytic activities. The synthesis condition was optimized using the Box-Behnken design method. The synthesized UL_AgNP showed the surface plasmon resonance peak at 458 nm. The optimized synthesis condition produced spherically shaped UL_AgNP with a size of 5.21 ± 1.92 nm and a zeta potential of -26.33 ± 0.93 mV. An X-ray diffraction analysis exhibited intense Bragg's reflection peaks at (111), (200), (220), and (311), having a face-centered cubic structure of AgNP. Attenuated total reflectance-Fourier-transform infrared spectroscopy and energy-dispersive X-ray spectroscopy further confirmed the presence of silver in the synthesized UL_AgNP. The brine shrimp lethality test of UL_AgNP reported a lethal concentration 50 value of <7.8 μg/mL after 24 h. The UL_AgNP exhibited antiproliferative activity against MCF-7 cells with a half-maximal inhibitory concentration value of 4.96 ± 0.31 μg/mL by inducing S-phase cell cycle arrest, apoptotic effect, and reduction of cell migration. Furthermore, UL_AgNP proved its efficient photocatalytic activity against methylene blue dye (50.22 % ± 0.06 %, after 10 min at a concentration of 50 μg/mL). Therefore, the UL_AgNP exhibited promising antiproliferative activity against MCF-7 cells, highlighting their potential as a therapeutic agent. Further investigations are needed to elucidate the precise mechanism of their action.
  4. Alginate coated mesoporous silica nanoparticles as oral delivery carrier of curcumin and quercetin to colon cancer: preparation, optimization, characterization, and anticancer activity
    Alallam B, Abdkadir E, Hayati A, Keong YY, Lim V
    Drug Deliv Transl Res, 2025 Jan 12.
    PMID: 39800814 DOI: 10.1007/s13346-024-01777-6
    The synergistic bioactive effect of polyphenols can enhance the development of functional foods to prevent chronic diseases such as cancer. Curcumin and quercetin have been shown to possess anticancer properties. The combination of curcumin and quercetin has been shown to provide synergistic effects against cancer cell proliferation. The prospect of exhibiting a synergistic antitumor effect is to target a multi-pathway approach, reduce dosage, and minimize potential side effects. However, their effectiveness is limited by poor bioavailability. Nanoscale delivery systems are promising strategies for the delivery of polyphenols. Nevertheless, many of these nanomaterials are yet to be commercialized owing to their lack of versatility or manufacturing costs. Thus, developing a formulation that responds to body conditions is a great challenge and would provide a better way to orally administer polyphenols. Therefore, this study aimed to develop a dual-responsive disulfide-linked core-shell nanohybrid for oral delivery and targeted release of polyphenols in the colon. The nanohybrid had monodispersed structures with a size of  9.5 nm), surface area of > 700 m2/g, and zeta potential of - 30.71 ± 0.71 mV. The polyphenols were encapsulated into the nanohybrid in their amorphous state, with a loading capacity of 20.49%. The coating enhanced the release of polyphenols into the intestinal fluid, potentially improving their delivery to the colon. The nanohybrid demonstrated a better anticancer effect than the free polyphenols against HT29 cancer cells. This study explores the use of a dual-sensitive alginate-coated mesoporous silica nanohybrid as a carrier for the enhanced delivery of polyphenols.
  5. Silver nanoparticles Clinacanthus Nutans leaves extract induced apoptosis towards oral squamous cell carcinoma cell lines
    Yakop F, Abd Ghafar SA, Yong YK, Saiful Yazan L, Mohamad Hanafiah R, Lim V, et al.
    Artif Cells Nanomed Biotechnol, 2018;46(sup2):131-139.
    PMID: 29561182 DOI: 10.1080/21691401.2018.1452750
    PURPOSE: The purpose of this study was to investigate apoptotic activity of silver nanoparticle Clinacanthus nutans (AgNps-CN) towards HSC-4 cell lines (oral squamous cell carcinoma cell lines).

    METHODS: Methods involved were MTT assay (cytotoxic activity), morphological cells analysis, flow cytometry and cell cycle analysis and western blot.

    RESULTS: MTT assay revealed IC50 concentration was 1.61 µg/mL, 3T3-L1 cell lines were used to determine whether AgNps-CN is cytotoxic to normal cells. At the highest concentration (3 µg/mL), no cytotoxic activity has been observed. Flow cytometry assay revealed AgNps-CN caused apoptosis effects towards HSC-4 cell lines with significant changes were observed at G1 phase when compared with untreated cells. Morphological cells analysis revealed that most of the cells exhibit apoptosis characteristics rather than necrosis. Protein study revealed that ratio of Bax/Bcl-2 increased mainly due to down-regulation of Bcl-2 expression.

    CONCLUSION: AgNps-CN have shown potential in inhibiting HSC-4 cell lines. IC50 was low compared to few studies involving biosynthesized of silver nanoparticles. Apoptosis effects were shown towards HSC-4 cell lines by the increased in Bax/Bcl-2 protein ratio. Further study such as PCR or in vivo studies are required.

  6. Biocompatible disulphide cross-linked sodium alginate derivative nanoparticles for oral colon-targeted drug delivery
    Ayub AD, Chiu HI, Mat Yusuf SNA, Abd Kadir E, Ngalim SH, Lim V
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):353-369.
    PMID: 30691309 DOI: 10.1080/21691401.2018.1557672
    The application of layer-by-layer (LbL) approach on nanoparticle surface coating improves the colon-specific drug delivery of insoluble drugs. Here, we aimed to formulate a self-assembled cysteamine-based disulphide cross-linked sodium alginate with LbL self-assembly to improve the delivery of paclitaxel (PCX) to colonic cancer cells. Cysteamine was conjugated to the backbone of oxidized SA to form a core of self-assembled disulphide cross-linked nanospheres. P3DL was selected for PCX loading and fabricated LbL with poly(allylamine hydrochloride) (PAH) and poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSCMA) resulting from characterization and drug release studies. P3DL-fabricated PCX-loaded nanospheres (P3DL/PAH/PSSCMA) exhibited an encapsulation efficiency of 77.1% with cumulative drug release of 45.1%. Dynamic light scattering analysis was reported at 173.6 ± 2.5 nm with polydispersity index of 0.394 ± 0.105 (zeta potential= -58.5 mV). P3DL/PAH/PSSCMA demonstrated a pH-dependent swelling transition; from pH 1 to 7 (102.2% increase). The size increased by 33.0% in reduction response study after incubating with 10 mM glutathione (day 7). HT-29 cells showed high viabilities (86.7%) after treatment with the fabricated nanospheres at 0.8 µg/mL. Cellular internalization was successful with more than 70.0% nanospheres detected in HT-29 cells. Therefore, this fabricated nanospheres may be considered as potential nanocarriers for colon cancer-targeted chemotherapeutic drug delivery.
  7. Fulltext Characterisation and Evaluation of Trimesic Acid Derivatives as Disulphide Cross-Linked Polymers for Potential Colon Targeted Drug Delivery
    Mat Yusuf SNA, Ng YM, Ayub AD, Ngalim SH, Lim V
    Polymers (Basel), 2017 Jul 27;9(8).
    PMID: 30970988 DOI: 10.3390/polym9080311
    Discovery and use of biocompatible polymers offers great promise in the pharmaceutical field, particularly in drug delivery systems. Disulphide bonds, which commonly occur in peptides and proteins and have been used as drug-glutathione conjugates, are reductively cleaved in the colon. The intrinsic stability of a disulphide relative to thiol groups is determined by the redox potential of the environment. The objective of this study was to synthesise a trimesic acid-based disulphide cross-linked polymer that could potentially be used for targeted delivery to the colon. The monomer was synthesised by an amide coupling reaction between trimesic acid and (triphenylmethyl) thioethylamine using a two-step synthesis method. The s-trityl group was removed using a cocktail of trifluoroacetic acid and triethylsilane to expose the thiols in preparation for further polymerisation. The resulting polymers (P10, P15, P21, P25, and P51, generated using different molar ratios) were reduced after 1.5 h of reduction time. Scanning electron microscopy images of the polymers showed spherical, loose, or tight patterns depending on the molar ratio of polymerisation. These polymers also exhibited efficient dissolution under various gastrointestinal conditions. Of the five polymers tested, P10 and P15 appeared to be promising drug delivery vehicles for poorly soluble drugs, due to the hydrophobic nature of the polymers.
  8. Antiangiogenic properties of nanoparticles: a systematic review
    Saeed BA, Lim V, Yusof NA, Khor KZ, Rahman HS, Abdul Samad N
    Int J Nanomedicine, 2019;14:5135-5146.
    PMID: 31371952 DOI: 10.2147/IJN.S199974
    Nanoparticles appear to be one of the most promising agents that offer efficacy in angiogenesis-related disease therapy. The objective of this research is to systematically review studies that have probed into the effect of nanoparticles on angiogenesis. Selected inclusion criteria were used to extract articles, references that were cited in the initial search were sought to identify more potential articles, and articles that did not meet the inclusion criteria and duplicates were discarded. The spherical shape was shown to be the most common shape employed to investigate the role of nanoparticles in angiogenesis therapy. The size of nanoparticles appears to play a crucial role for efficacy on angiogenesis, in which 20 nm emerged as the preferred size. Gold nanoparticles exhibit the most promise as an antiangiogenesis agent, and the toxicity was adjustable based on the dosages applied.
  9. Fulltext Extracellular matrix from decellularized mesenchymal stem cells improves cardiac gene expressions and oxidative resistance in cardiac C-kit cells
    Ng WH, Ramasamy R, Yong YK, Ngalim SH, Lim V, Shaharuddin B, et al.
    Regen Ther, 2019 Dec;11:8-16.
    PMID: 31193142 DOI: 10.1016/j.reth.2019.03.006
    OBJECTIVE: Myocardial infarction remains the number one killer disease worldwide. Cellular therapy using cardiac c-kit cells (CCs) are capable of regenerating injured heart. Previous studies showed mesenchymal stem cell-derived (MSC) extracellular matrices can provide structural support and are capable of regulating stem cell functions and differentiation. This study aimed to evaluate the effects of human MSC-derived matrices for CC growth and differentiation.

    METHODS: Human Wharton's Jelly-derived MSCs were cultured in ascorbic acid supplemented medium for 14 days prior to decellularisation using two methods. 1% SDS/Triton X-100 (ST) or 20 mM ammonia/Triton X-100 (AT). CCs isolated from 4-week-old C57/BL6N mice were cultured on the decellularised MSC matrices, and induced to differentiate into cardiomyocytes in cardiogenic medium for 21 days. Cardiac differentiation was assessed by immunocytochemistry and qPCR. All data were analysed using ANOVA.

    RESULTS: In vitro decellularisation using ST method caused matrix delamination from the wells. In contrast, decellularisation using AT improved the matrix retention up to 30% (p 

  10. Fulltext Human Wharton's Jelly-Derived Mesenchymal Stem Cells Minimally Improve the Growth Kinetics and Cardiomyocyte Differentiation of Aged Murine Cardiac c-kit Cells in In Vitro without Rejuvenating Effect
    Ng WH, Yong YK, Ramasamy R, Ngalim SH, Lim V, Shaharuddin B, et al.
    Int J Mol Sci, 2019 Nov 06;20(22).
    PMID: 31698679 DOI: 10.3390/ijms20225519
    Cardiac c-kit cells show promise in regenerating an injured heart. While heart disease commonly affects elderly patients, it is unclear if autologous cardiac c-kit cells are functionally competent and applicable to these patients. This study characterised cardiac c-kit cells (CCs) from aged mice and studied the effects of human Wharton's Jelly-derived mesenchymal stem cells (MSCs) on the growth kinetics and cardiac differentiation of aged CCs in vitro. CCs were isolated from 4-week- and 18-month-old C57/BL6N mice and were directly co-cultured with MSCs or separated by transwell insert. Clonogenically expanded aged CCs showed comparable telomere length to young CCs. However, these cells showed lower Gata4, Nkx2.5, and Sox2 gene expressions, with changes of 2.4, 3767.0, and 4.9 folds, respectively. Direct co-culture of both cells increased aged CC migration, which repopulated 54.6 ± 4.4% of the gap area as compared to aged CCs with MSCs in transwell (42.9 ± 2.6%) and CCs without MSCs (44.7 ± 2.5%). Both direct and transwell co-culture improved proliferation in aged CCs by 15.0% and 16.4%, respectively, as traced using carboxyfluorescein succinimidyl ester (CFSE) for three days. These data suggest that MSCs can improve the growth kinetics of aged CCs. CCs retaining intact telomere are present in old hearts and could be obtained based on their self-renewing capability. Although these aged CCs with reduced growth kinetics are improved by MSCs via cell-cell contact, the effect is minimal.
  11. Suppressing growth, migration, and invasion of human hepatocellular carcinoma HepG2 cells by Catharanthus roseus‑silver nanoparticles
    Azhar NA, Ghozali SZ, Abu Bakar SA, Lim V, Ahmad NH
    Toxicol In Vitro, 2020 Sep;67:104910.
    PMID: 32526345 DOI: 10.1016/j.tiv.2020.104910
    Application of silver nanoparticles serves as a new approach in cancer treatment due to its unique features. Biosynthesis of silver nanoparticles using plant is advantageous since they are easily accessible, nontoxic and produce quicker reaction compared to other methods. To evaluate the cytotoxicity, mechanism of cell death and DNA damage of biosynthesized Catharanthus roseus-silver nanoparticles on human liver cancer (HepG2) cells. The antiproliferative activity of Catharanthus roseus‑silver nanoparticles was measured using MTT assay. The cytotoxic effects were further evaluated by measuring nitric oxide and reactive oxygen species (ROS). The mechanism of cell death was determined by annexin-FITC/propidium iodide, mitochondrial membrane potential (MMP) and cell cycle assays. The assessment of DNA damage was evaluated using Comet assay method. The uptake of the nanoparticles were evaluated by Transmission Electron Microscopy (TEM). Catharanthus roseus‑silver nanoparticles has inhibited the proliferation of HepG2 cells in a time-dependent manner with a median IC50 value of 3.871 ± 0.18 μg/mL. The concentration of nitrite and ROS were significantly higher than control. The cell death was due to apoptosis associated with MMP loss, cell cycle arrest, and extensive DNA damage. TEM analysis indicated the presence of free nanoparticles and endosomes containing the nanoparticles. The findings show that Catharanthus roseus‑silver nanoparticles have produced cytotoxic effects on HepG2 cells and thus may have a potential to be used as an anticancer treatment, particularly for hepatocellular carcinoma.
  12. Fulltext Optimization of biogenic synthesis of silver nanoparticles from flavonoid-rich Clinacanthus nutans leaf and stem aqueous extracts
    Mat Yusuf SNA, Che Mood CNA, Ahmad NH, Sandai D, Lee CK, Lim V
    R Soc Open Sci, 2020 Jul;7(7):200065.
    PMID: 32874618 DOI: 10.1098/rsos.200065
    Background: Silver nanoparticles (AgNPs) are widely used in food industries, biomedical, dentistry, catalysis, diagnostic biological probes and sensors. The use of plant extract for AgNPs synthesis eliminates the process of maintaining cell culture and the process could be scaled up under a non-aseptic environment. The purpose of this study is to determine the classes of phytochemicals, to biosynthesize and characterize the AgNPs using Clinacanthus nutans leaf and stem extracts. In this study, AgNPs were synthesized from the aqueous extracts of C. nutans leaves and stems through a non-toxic, cost-effective and eco-friendly method. Results: The formation of AgNPs was confirmed by UV-Vis spectroscopy, and the size of AgNP-L (leaf) and AgNP-S (stem) were 114.7 and 129.9 nm, respectively. Transmission electron microscopy (TEM) analysis showed spherical nanoparticles with AgNP-L and AgNP-S ranging from 10 to 300 nm and 10 to 180 nm, with average of 101.18 and 75.38 nm, respectively. The zeta potentials of AgNP-L and AgNP-S were recorded at -42.8 and -43.9 mV. X-ray diffraction analysis matched the face-centred cubic structure of silver and was capped with bioactive compounds. Fourier transform infrared spectrophotometer analysis revealed the presence of few functional groups of phenolic and flavonoid compounds. These functional groups act as reducing agents in AgNPs synthesis. Conclusion: These results showed that the biogenically synthesized nanoparticles reduced silver ions to silver nanoparticles in aqueous condition and the AgNPs formed were stable and less toxic.
  13. Response surface methodology optimization of polyhydroxyalkanoate production by Burkholderia cepacia BPT1213 using waste glycerol from palm oil-based biodiesel production
    Mohd Zain NF, Paramasivam M, Tan JS, Lim V, Lee CK
    Biotechnol Prog, 2021 01;37(1):e3077.
    PMID: 32894656 DOI: 10.1002/btpr.3077
    The feasibility of using waste glycerol from the biodiesel industry for biosynthesis of polyhydroxyalkanoate (PHA) by Burkholderia cepacia BPT1213 was evaluated. Culture conditions were optimized by growing B. cepacia BPT1213 in mineral salt medium supplemented with 2% waste glycerol in a 2.5 L bioreactor. Response surface methodology was used to determine the influence of aeration rate (0.6-1.8 vvm), agitation speed (100-300 rpm), and cultivation period (48-72 hr) on PHA production. The optimum conditions for the growth and PHA accumulation were 1.5 vvm, 300 rpm, and 72 hr, with predicted values of 5.08 g/L cell dry weight (CDW), 66.07% PHA content, and 3.35 g/L total PHA concentration. Using these conditions, the experimental system produced 5.63 g/L of CDW with 64.00% wt/wt PHA content, which is threefold higher PHA concentration (3.60 g/L) compared to the non-optimized conditions. The melting temperature (Tm ) of purified PHA was 173.45 ± 1.05°C. In conclusion, the statistical approach was significantly increased the PHA production using waste glycerol as the sole carbon source.
  14. Fulltext Mechanistic Actions between Garcinia atroviridis Essential Oil and 2 Deoxy-d-glucose in Cultured PANC-1 Human Pancreatic Cancer Cells
    Nik Mohamed Kamal NNS, Abdul Aziz FA, Tan WN, Fauzi AN, Lim V
    Molecules, 2021 Jun 09;26(12).
    PMID: 34207699 DOI: 10.3390/molecules26123518
    Pancreatic cancer is an aggressive disease that progresses in a relatively symptom-free manner; thus, is difficult to detect and treat. Essential oil is reported to exhibit pharmacological properties, besides its common and well-known function as aromatherapy. Therefore, this study herein aimed to investigate the anti-proliferative effect of essential oil extracted from leaves of Garcinia atroviridis (EO-L) against PANC-1 human pancreatic cancer cell line. The cell growth inhibitory concentration at 50% (IC50) and selective index (SI) values of EO-L analyses were determined as 78 µg/mL and 1.23, respectively. Combination index (CI) analysis revealed moderate synergism (CI values of 0.36 to 0.75) between EO-L and 2 deoxy-d-glucose (2-DG) treatments. The treatments of PANC-1 cells with EO-L, 2-DG and EOL+2DG showed evidence of depolarization of mitochondrial membrane potential, cell growth arrest and apoptosis. The molecular mechanism causing the anti-proliferative effect between EO-L and 2-DG is potentially through pronounced up-regulation of P53 (4.40-fold), HIF1α (1.92-fold), HK2 (2.88-fold) and down-regulation of CYP3A5 (0.11-fold), as supported by quantitative mRNA expression analysis. Collectively, the current data suggest that the combination of two anti-proliferative agents, EO-L and 2-DG, can potentially be explored as therapeutic treatments and as potentiating agents to conventional therapy against human pancreatic cancer.
  15. Exploring a novel deep eutectic solvents combined with vortex assisted dispersive liquid-liquid microextraction and its toxicity for organophosphorus pesticides analysis from honey and fruit samples
    Elencovan V, Joseph J, Yahaya N, Abdul Samad N, Raoov M, Lim V, et al.
    Food Chem, 2021 Aug 10;368:130835.
    PMID: 34416487 DOI: 10.1016/j.foodchem.2021.130835
    A novel deep eutectic solvents (DES) was successfully applied as an emulsifier in vortex assisted liquid-liquid microextraction (VALLME) coupled with gas chromatography-mass spectrometry for the determination of organophosphorus pesticides in honey and fruit samples. Based on the result of toxicity study, DES provides new opportunities for the safe delivery and application. The predominant parameters affecting extraction efficiency were thoroughly optimized and studied in detail. Under optimum parameters, the calibration curve was determined in the concentration range of 0.1 to 200 µgL-1 with excellent determination coefficients values of 0.9989 to 0.9999. Limit of detection and limit of quantification were found to be 0.01 - 0.09 µgL-1 and 0.03 - 0.2 µgL-1, respectively. Application of the developed method to honey and fruit samples gave acceptable recovery values 83 - 109% with relative standard deviation below than 9.5%. The suggested approach has also proven to be simple, cost-effective, rapid, and non-toxic in nature.
  16. Fulltext In vitro Anticancer Effects of Vernonia amygdalina Leaf Extract and Green-Synthesised Silver Nanoparticles
    Joseph J, Khor KZ, Moses EJ, Lim V, Aziz MY, Abdul Samad N
    Int J Nanomedicine, 2021;16:3599-3612.
    PMID: 34079252 DOI: 10.2147/IJN.S303921
    Purpose: Vernonia amygdalina (VA) is a traditional African herbal medicine that has been reported to possess anticancer properties. However, the anticancer properties of VA silver nanoparticles have not been studied. The aim of the study was to examine and evaluate the anticancer activities of VA leaf extracts and VA silver nanoparticles on the human breast cancer cell line, MCF-7.

    Methods: VA leaves were extracted using sequential extraction assisted with ultrasound using three different solvents: ethanol, 50% ethanol, and deionized water. The silver nanoparticles were synthesised with VA aqueous extract.

    Results: The ethanol extract and VA silver nanoparticles inhibit MCF-7 cell proliferation with an average half-maximal inhibitory concentration (IC50) value of 67µg/mL and 6.11µg/mL, respectively, after 72 hours of treatment. The ethanol extract and VA silver nanoparticles also caused G1 phase cell cycle arrest, induced apoptosis and nuclear fragmentation in MCF-7 cells.

    Conclusion: VA ethanol extracts and VA silver nanoparticles decreased the cell viability in MCF-7 cells in a time and dose-dependent manner by inducing apoptosis and causing DNA damage. Further research is needed to elucidate the mechanism of action of VA leaf extracts and VA silver nanoparticles. This study is the first to report on the anticancer activity of VA silver nanoparticles in MCF-7 cells.

  17. Fulltext Tualang honey improves human corneal epithelial progenitor cell migration and cellular resistance to oxidative stress in vitro
    Tan JJ, Azmi SM, Yong YK, Cheah HL, Lim V, Sandai D, et al.
    PLoS One, 2014;9(5):e96800.
    PMID: 24802273 DOI: 10.1371/journal.pone.0096800
    Stem cells with enhanced resistance to oxidative stress after in vitro expansion have been shown to have improved engraftment and regenerative capacities. Such cells can be generated by preconditioning them with exposure to an antioxidant. In this study we evaluated the effects of Tualang honey (TH), an antioxidant-containing honey, on human corneal epithelial progenitor (HCEP) cells in culture. Cytotoxicity, gene expression, migration, and cellular resistance to oxidative stress were evaluated. Immunofluorescence staining revealed that HCEP cells were holoclonal and expressed epithelial stem cell marker p63 without corneal cytokeratin 3. Cell viability remained unchanged after cells were cultured with 0.004, 0.04, and 0.4% TH in the medium, but it was significantly reduced when the concentration was increased to 3.33%. Cell migration, tested using scratch migration assay, was significantly enhanced when cells were cultured with TH at 0.04% and 0.4%. We also found that TH has hydrogen peroxide (H2O2) scavenging ability, although a trace level of H2O2 was detected in the honey in its native form. Preconditioning HCEP cells with 0.4% TH for 48 h showed better survival following H2O2-induced oxidative stress at 50 µM than untreated group, with a significantly lower number of dead cells (15.3 ± 0.4%) were observed compared to the untreated population (20.5 ± 0.9%, p<0.01). Both TH and ascorbic acid improved HCEP viability following induction of 100 µM H2O2, but the benefit was greater with TH treatment than with ascorbic acid. However, no significant advantage was demonstrated using 5-hydroxymethyl-2-furancarboxaldehyde, a compound that was found abundant in TH using GC/MS analysis. This suggests that the cellular anti-oxidative capacity in HCEP cells was augmented by native TH and was attributed to its antioxidant properties. In conclusion, TH possesses antioxidant properties and can improve cell migration and cellular resistance to oxidative stress in HCEP cells in vitro.
  18. Green synthesis, characterisation and antibacterial activities of Strobilanthes crispus-mediated silver nanoparticles (SC-AGNPS) against selected bacteria
    Mohamad Hanafiah R, Abd Ghafar SA, Lim V, Musa SNA, Yakop F, Hairil Anuar AH
    Artif Cells Nanomed Biotechnol, 2023 Dec;51(1):549-559.
    PMID: 37847252 DOI: 10.1080/21691401.2023.2268167
    This study aims to characterize and determine the antibacterial activities of synthesized Strobilanthes crispus-mediated AgNPs (SC-AgNPs) against Streptococcus mutans, Escherichia coli and Pseudomonas aeruginosa. S. crispus water extract acts as a reducing and capping agent in the synthesis of AgNPs. The synthesized AgNPs were characterized by using UV-Vis spectrophotometer, dynamic light scattering (DLS), field emission scanning electron microscope (FESEM), X-ray diffractometer (XRD) and Fourier transform infra-red (FTIR). FESEM images showed a rough surface with a spherical shape. The average size distribution of 75.25 nm with a polydispersity index (PDI) of 0.373. XRD analysis matched the face-centred cubic structure of silver. FTIR analysis revealed a shifted peak from 1404.99 to 1345.00 cm-1. MIC and MBC values of SC-AgNPs were 1.25 mg/mL and 2.5 mg/mL against E. coli, P. aeruginosa and S. mutans, respectively. Time-kill assay showed that SC-AgNPs significantly reduced bacterial growth as compared to non-treated bacteria. Morphologies of bacteria treated with SC-AgNPs were shrunk, lysed, irregular and smaller as compared to control. SC-AgNPs significantly disrupted the gene expression of eae A, gtf B and Pel A (p 
  19. Fulltext Cytotoxicity of Plant-Mediated Synthesis of Metallic Nanoparticles: A Systematic Review
    Hanan NA, Chiu HI, Ramachandran MR, Tung WH, Mohamad Zain NN, Yahaya N, et al.
    Int J Mol Sci, 2018 Jun 11;19(6).
    PMID: 29891772 DOI: 10.3390/ijms19061725
    In the field of medicine, nanomaterials, especially those derived using the green method, offer promise as anti-cancer agents and drug carriers. However, the biosafety of metallic nanoparticles used as anti-cancer agents remains a concern. The goal of this systematic review was to compare the cytotoxicity of different plant-mediated syntheses of metallic nanoparticles based on their potency, therapeutic index, and cancer cell type susceptibility in the hopes of identifying the most promising anti-cancer agents. A literature search of electronic databases including Science Direct, PubMed, Springer Link, Google Scholar, and ResearchGate, was conducted to obtain research articles. Keywords such as biosynthesis, plant synthesis, plant-mediated, metallic nanoparticle, cytotoxicity, and anticancer were used in the literature search. All types of research materials that met the inclusion criteria were included in the study regardless of whether the results were positive, negative, or null. The therapeutic index was used as a safety measure for the studied compound of interest. Data from 76 selected articles were extracted and synthesised. Seventy-two studies reported that the cytotoxicity of plant-mediated synthesis of metallic nanoparticles was time and/or dose-dependent. Biosynthesised silver nanoparticles demonstrated higher cytotoxicity potency compared to gold nanoparticles synthesised by the same plants (Plumbago zeylanica, Commelina nudiflora, and Cassia auriculata) irrespective of the cancer cell type tested. This review also identified a correlation between the nanoparticle size and morphology with the potency of cytotoxicity. Cytotoxicity was found to be inversely proportional to nanoparticle size. The plant-mediated syntheses of metallic nanoparticles were predominantly spherical or quasi-spherical, with the median lethal dose of 1⁻20 µg/mL. Nanoparticles with other shapes (triangular, hexagonal, and rods) were less potent. Metallic nanoparticles synthesised by Abutilon inducum, Butea monosperma, Gossypium hirsutum, Indoneesiella echioides, and Melia azedarach were acceptably safe as anti-cancer agents, as they had a therapeutic index of >2.0 when tested on both cancer cells and normal human cells. Most plant-mediated syntheses of metallic nanoparticles were found to be cytotoxic, although some were non-cytotoxic. The results from this study suggest a focus on a selected list of potential anti-cancer agents for further investigations of their pharmacodynamic/toxicodynamic and pharmacokinetic/toxicokinetic actions with the goal of reducing the Global Burden of Diseases and the second leading cause of mortality.
  20. Fulltext Synergistic effects of combined cisplatin and Clinacanthus nutans extract on triple negative breast cancer cells
    Abu Bakar NFAB, Yeo ZL, Hussin F, Madhavan P, Lim V, Jemon K, et al.
    J Taibah Univ Med Sci, 2023 Dec;18(6):1220-1236.
    PMID: 37250812 DOI: 10.1016/j.jtumed.2023.04.003
    OBJECTIVE: Triple negative breast cancer (TNBC) is the most invasive breast cancer subtype enriched with cancer stem cells. TNBCs do not express estrogen, progesterone, or human epidermal growth factor receptor 2 (HER2) receptors, making them difficult to be targeted by existing chemotherapy treatments. In this study, we attempted to identify the effects of combined cisplatin and Clinacanthus nutans treatment on MDA-MD-231 and MDA-MB-468 breast cancer cells, which represent TNBC subtypes.

    METHODS: The phytochemical fingerprint of C. nutans ethanolic leaf extract was evaluated by LC-MS/MS analysis. We investigated the effects of cisplatin (0-15.23 μg/mL), C. nutans (0-50 μg/mL), and a combination of cisplatin (3.05 μg/mL) and C. nutans (0-50 μg/mL), on cell viability, proliferation, apoptosis, invasion, mRNA expression in cancer stem cells (CD49f, KLF4), and differentiation markers (TUBA1A, KRT18) in TNBC cells. In addition, we also studied the interaction between cisplatin and C. nutans.

    RESULTS: Derivatives of fatty acids, carboxylic acid ester, and glycosides, were identified as the major bioactive compounds with potential anticancer properties in C. nutans leaf extract. Reductions in cell viability (0-78%) and proliferation (2-77%), as well as a synergistic anticancer effect, were identified in TNBC cells when treated with a combination of cisplatin and C. nutans. Furthermore, apoptotic induction via increased caspase-3/7 activity (MDA-MB-231: 2.73-fold; MDA-MB-468: 3.53-fold), and a reduction in cell invasion capacity to 36%, were detected in TNBC cells when compared to single cisplatin and C. nutans treatments. At the mRNA level, cisplatin and C. nutans differentially regulated specific genes that are responsible for proliferation and differentiation.

    CONCLUSION: Our findings demonstrate that the combination of cisplatin and C. nutans represents a potential treatment for TNBC.

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