Displaying publications 81 - 100 of 1782 in total

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  1. Fulltext Anti-senescence effects of 4-methoxychalcone and 4-bromo-4'-methoxychalcone on human endothelial cells
    Tien XY, Lee YK, Wong PF, Khor YS, Murugan DD, Abdullah I
    Drug Discov Ther, 2024;18(3):199-206.
    PMID: 38987208 DOI: 10.5582/ddt.2024.01034
    Senolytics are drugs that specifically target senescent cells. Flavonoids such as quercetin and fisetin possess selective senolytic activities. This study aims to investigate if chalcones exhibit anti-senescence activities. Anti-senescence effect of 11 chalcone derivatives on the replicative senescence human aortic endothelial cells (HAEC) and human fetal lung fibroblasts (IMR90) was evaluated. Compound 2 (4-methoxychalcone) and compound 4 (4-bromo-4'-methoxychalcone) demonstrated increased cytotoxicity in senescent HAEC compared to young HAEC, with significant differences on IC50 values. Their anti-senescence effects on HAEC exceeded fisetin. Higher selectivity of compound 4 toward HAEC over IMR90 could be attributed to 4-methoxy (4-OMe) substitution at ring A (R1). Chalcone derivatives have potentials as senolytics in mitigating replicative senescence, warranting further research and development on chalcones as anti-senescent agent.
    Matched MeSH terms: Cell Line
  2. Fulltext ROS-generating alginate-coated gold nanorods as biocompatible nanosonosensitisers for effective sonodynamic therapy of cancer
    Loke YL, Beishenaliev A, Wang PW, Lin CY, Chang CY, Foo YY, et al.
    Ultrason Sonochem, 2023 Jun;96:106437.
    PMID: 37187119 DOI: 10.1016/j.ultsonch.2023.106437
    Sonodynamic therapy (SDT) emerges as a promising non-invasive alternative for eradicating malignant tumours. However, its therapeutic efficacy remains limited due to the lack of sonosensitisers with high potency and biosafety. Previously, gold nanorods (AuNRs) have been extensively studied for their applications in photodynamic or photothermal cancer therapy, but their sonosensitising properties are largely unexplored. Here, we reported the applicability of alginate-coated AuNRs (AuNRsALG) with improved biocompatibility profiles as promising nanosonosensitisers for SDT for the first time. AuNRsALG were found stable under ultrasound irradiation (1.0 W/cm2, 5 min) and maintained structural integrity for 3 cycles of irradiation. The exposure of the AuNRsALG to ultrasound irradiation (1.0 W/cm2, 5 min) was shown to enhance the cavitation effect significantly and generate a 3 to 8-fold higher amount of singlet oxygen (1O2) than other reported commercial titanium dioxide nanosonosensitisers. AuNRsALG exerted dose-dependent sonotoxicity on human MDA-MB-231 breast cancer cells in vitro, with ∼ 81% cancer cell killing efficacy at a sub-nanomolar level (IC50 was 0.68 nM) predominantly through apoptosis. The protein expression analysis showed significant DNA damage and downregulation of anti-apoptotic Bcl-2, suggesting AuNRsALG induced cell death through the mitochondrial pathway. The addition of mannitol, a reactive oxygen species (ROS) scavenger, inhibited cancer-killing effect of AuNRsALG-mediated SDT, further verifying that the sonotoxicity of AuNRsALG is driven by the production of ROS. Overall, these results highlight the potential application of AuNRsALG as an effective nanosonosensitising agent in clinical settings.
    Matched MeSH terms: Cell Line, Tumor
  3. Apoptotic Potential of Glucomoringin Isothiocyanate (GMG-ITC) Isolated from Moringa oleifera Lam Seeds on Human Prostate Cancer Cells (PC-3)
    Abd Karim NA, Adam AHB, Jaafaru MS, Rukayadi Y, Abdull Razis AF
    Molecules, 2023 Apr 04;28(7).
    PMID: 37049977 DOI: 10.3390/molecules28073214
    Inhibition of several protein pathways involved in cancer cell regulation is a necessary key in the discovery of cancer chemotherapy. Moringa oleifera Lam is often used in traditional medicine for the treatment of various illnesses. The plant contains glucomoringin isothiocyanate (GMG-ITC) with therapeutic potential against various cancer cells. Therefore, GMG-ITC was evaluated for its cytotoxicity against the PC-3 prostate cancer cell line and its potential to induce apoptosis. GMG-ITC inhibited cell proliferation in the PC-3 cell line with IC50 value 3.5 µg/mL. Morphological changes as a result of GMG-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GMG-ITC in a time-dependent manner. Moreover, GMG-ITC induced a time-dependent G2/M phase arrest, with reduction of 39.1% in the PC-3 cell line. GMG-ITC also activates apoptotic genes including caspase, tumor suppressor gene (p53), Akt/MAPK, and Bax of the proapoptotic Bcl family. Early apoptosis proteins (JNK, Bad, Bcl2, and p53) were significantly upregulated upon GMG-ITC treatment. It is concluded that apoptosis induction was observed in PC-3 cells treated with GMG-ITC. These phenomena suggest that GMG-ITC from M. oleifera seeds could be useful as a future cytotoxic agent against prostate cancer.
    Matched MeSH terms: Cell Line, Tumor
  4. Fulltext Antibacterial Activity of Ciprofloxacin-Encapsulated Cockle Shells Calcium Carbonate (Aragonite) Nanoparticles and Its Biocompatability in Macrophage J774A.1
    Isa T, Zakaria ZA, Rukayadi Y, Mohd Hezmee MN, Jaji AZ, Imam MU, et al.
    Int J Mol Sci, 2016;17(5).
    PMID: 27213349 DOI: 10.3390/ijms17050713
    The use of nanoparticle delivery systems to enhance intracellular penetration of antibiotics and their retention time is becoming popular. The challenge, however, is that the interaction of nanoparticles with biological systems at the cellular level must be established prior to biomedical applications. Ciprofloxacin-cockle shells-derived calcium carbonate (aragonite) nanoparticles (C-CSCCAN) were developed and characterized. Antibacterial activity was determined using a modified disc diffusion protocol on Salmonella Typhimurium (S. Typhimurium). Biocompatibilittes with macrophage were evaluated using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-Bromo-2'-deoxyuridine (BrdU) assays. Transcriptional regulation of interleukin 1 beta (IL-1β) was determined using reverse transcriptase-polymerase chain reaction (RT-PCR). C-CSCCAN were spherical in shape, with particle sizes ranging from 11.93 to 22.12 nm. Encapsulation efficiency (EE) and loading content (LC) were 99.5% and 5.9%, respectively, with negative ζ potential. X-ray diffraction patterns revealed strong crystallizations and purity in the formulations. The mean diameter of inhibition zone was 18.6 ± 0.5 mm, which was better than ciprofloxacin alone (11.7 ± 0.9 mm). Study of biocompatability established the cytocompatability of the delivery system without upregulation of IL-1β. The results indicated that ciprofloxacin-nanoparticles enhanced the antibacterial efficacy of the antibiotic, and could act as a suitable delivery system against intracellular infections.
    Matched MeSH terms: Cell Line
  5. A review of CRISPR-Cas and PCR-based methods for the detection of animal species in the food chain-current challenges and future prospects
    Sultana S, Azlan A, Mohd Desa MN, Mahyudin NA, Anburaj A
    Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2024 Mar;41(3):213-227.
    PMID: 38284970 DOI: 10.1080/19440049.2024.2304577
    Regular testing and systematic investigation play a vital role to ensure product safety. Until now, the existing food authentication techniques have been based on proteins, lipids, and nucleic acid-based assays. Among various deoxyribonucleic acid (DNA)-based methods, the recently developed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) based bio-sensing is an innovative and fast-expanding technology. The CRISPR/Cas-9 is known as Clustered Regularly Interspaced Short Palindromic Repeats due to the flexibility and simplicity of the CRISPR/Cas9 site-specific editing tool has been applied in many biological research areas such as Gene therapy, cell line development, discovering mechanisms of disease, and drug discovery. Nowadays, the CRISPR-Cas system has also been introduced into food authentication via detecting DNA barcodes of poultry and livestock both in processed and unprocessed food samples. This review documents various DNA based approaches, in an accessible format. Future CRISPR technologies are forecast while challenges are outlined.
    Matched MeSH terms: Cell Line
  6. Assessment of CXC ligand 12-mediated calcium signalling and its regulators in basal-like breast cancer cells
    Jamaludin SYN, Azimi I, Davis FM, Peters AA, Gonda TJ, Thompson EW, et al.
    Oncol Lett, 2018 Apr;15(4):4289-4295.
    PMID: 29541196 DOI: 10.3892/ol.2018.7827
    CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Ca2+signalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Ca2+responses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells. Cluster of differentiation (CD)24, the negative regulator of CXCL12 responses, demonstrated increased expression in MDA-MB-468 cells compared with MDA-MB-231 cells, and the two cell lines expressed comparable levels of hypoxia-inducible factor (HIF)2α, a CXCR4 regulator. Induction of epithelial-mesenchymal transition (EMT) by epidermal growth factor exhibited opposite effects on CXCR4 mRNA levels compared with hypoxia-induced EMT. Neither EMT inducer exhibited an effect on CXCR7 expression, however hypoxia increased HIF2α expression levels in MDA-MB-468 cells. Analysis of the gene expression profiles of breast tumours revealed that the highest expression levels of CXCR4 and CXCR7 were in the Claudin-Low molecular subtype, which is markedly associated with EMT features.
    Matched MeSH terms: Cell Line
  7. Fulltext Cathepsin-K inhibition enhances anti-cancerous activity within oral squamous cell carcinoma cells: Uncloaking the potency of new K21 formulation
    Imad R, Sheikh Z, Rao Pichika M, Kit-Kay M, Siddiqui RA, Nawaid Shah SN, et al.
    Exp Cell Res, 2023 Sep 01;430(1):113687.
    PMID: 37356748 DOI: 10.1016/j.yexcr.2023.113687
    BACKGROUND: The ability of cancer cells to be invasive and metastasize depend on several factors, of which the action of protease activity takes center stage in disease progression.

    PURPOSE/OBJECTIVE: To analyze function of new K21 molecule in the invasive process of oral squamous cell carcinoma (OSCC) cell line.

    MATERIALS & METHODS: The Fusobacterium (ATCC 23726) streaks were made, and pellets were resuspended in Cal27 (ATCC CRL-2095) OSCC cell line spheroid cell microplate. Cells were seeded and Lysotracker staining performed for CathepsinK red channel. Cell and morphology were evaluated using Transmission Electron microscopy. Thiobarbituric acid assay was performed. OSCC was analyzed for Mic60. Raman spectra were collected from the cancer cell line. L929 dermal fibroblast cells were used for Scratch Assay. ELISA muti arrays were used for cytokines and matrix molecules. Internalization ability of fibroblast cells were also analyzed. Structure of K21 as a surfactant molecule with best docked poses were presented.

    RESULTS: Decrease in lysosomal staining was observed after 15 and 30 min of 0.1% treatment. Tumor clusters were associated with cell membrane destruction in K21 primed cells. There was functional silencing of Mic60 via K21, especially with 1% concentration with reduced cell migration and invasiveness. Raman intensity differences were seen at 700 cm-1, 1200 cm-1 and 1600 cm-1 regions. EVs were detected within presence of fibroblast cells amongst K21 groups. Wound area and wound closure showed the progress of wound healing.

    CONCLUSION: Over expression of CatK can be reduced by a newly developed targeted K21 based drug delivery system leading to reduced migration and adhesion of oral squamous cell carcinoma cells. The K21 drug formulation can have great potential for cancer therapies due to targeting and cytotoxicity effects.

    Matched MeSH terms: Cell Line, Tumor
  8. Gold nanoparticles-based photothermal therapy for breast cancer
    Dheyab MA, Aziz AA, Khaniabadi PM, Jameel MS, Oladzadabbasabadi N, Rahman AA, et al.
    Photodiagnosis Photodyn Ther, 2023 Jun;42:103312.
    PMID: 36731732 DOI: 10.1016/j.pdpdt.2023.103312
    AuNPs-mediated photothermal therapy (PTT) is gaining popularity in both laboratory research and medical applications. It has proven clear advantages in breast cancer therapy over conventional thermal ablation because of its easily-tuned features of irradiation light with inside hyperthermia ability. Notwithstanding this significant progress, the therapeutic potential of AuNPs-mediated PTT in cancer treatments is still impeded by several challenges, including inherent non-specificity, low photothermal conversion effectiveness, and the limitation of excitation light tissue penetration. Given the rapid progress of AuNPs-mediated PTT, we present a comprehensive overview of significant breakthroughs in the recent advancements of AuNPs for PTT, focusing on breast cancer cells. With the improvement of chemical synthesis technology, AuNPs of various sizes and shapes with desired properties can be synthesized, allowing breast cancer targeting and treatment. In this study, we summarized the different sizes and features of four major types of AuNPs in this review: Au nanospheres, Au nanocages, Au nanoshells, and Au nanorods, and explored their benefits and drawbacks in PTT. We also discussed the diagnostic, bioconjugation, targeting, and cellular uptake of AuNPs, which could improve the performance of AuNP-based PTT. Besides that, potential challenges and future developments of AuNP-mediated PTT for clinical applications are discussed. AuNP-mediated PTT is expected to become a highly promising avenue in cancer treatment in the near future.
    Matched MeSH terms: Cell Line, Tumor
  9. Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance
    Hashemi M, Sabouni E, Rahmanian P, Entezari M, Mojtabavi M, Raei B, et al.
    Cell Mol Biol Lett, 2023 Apr 21;28(1):33.
    PMID: 37085753 DOI: 10.1186/s11658-023-00438-9
    Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial-mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC.
    Matched MeSH terms: Cell Line, Tumor
  10. Andrographolide Induces Apoptosis in Gastric Cancer Cells through Reactivation of p53 and Inhibition of Mdm-2
    Gao H, Li H, Liu W, Mishra SK, Li C
    Dokl Biochem Biophys, 2021 Sep;500(1):393-401.
    PMID: 34697748 DOI: 10.1134/S1607672921050070
    Andrographolide is a labdane diterpenoid isolated from Andrographis paniculata. The plant extract and andrographolide has long been used in traditional medicine practices mainly for gastrointestinal diseases and improving liver function. Andrographolide has shown various pharmacological properties including anti-inflammatory, antioxidant and anticancer activity. This study evaluated the effect of andrographolide on proliferation of human gastric carcinoma cells in relevance to p53 and Mdm-2 pathways. Andrographolide inhibited the proliferation of SGC7901 and AGS cells in a dose-dependent manner with estimated IC50 values 38 and 44 μM respectively. Effect of andrographolide on p53 activity was ascertained by using a p53 activator (RITA) which showed synergistic inhibition of cell proliferation. While andrographolide when used in combination with a p53 inhibitor (pifithrin-α) showed potent restriction over its response. Andrographolide caused decrease in mitochondrial membrane potential as an indicator of apoptotic activity. Andrographolide activated the expression of p53 protein and gene and downregulated the levels of Mdm-2 (negative regulator of p53). Andrographolide inhibited the colony formation abilities in SGC7901 in a p53-dependent manner followed by induction of mitochondrial intrinsic apoptosis through activation of caspases-9 and -3, cleavage of PARP, and inhibition of pro-apoptotic Bcl-2. Andrographolide induced p53 mediated apoptosis in gastric carcinoma cells which adds to a novel approach in anticancer therapies.
    Matched MeSH terms: Cell Line, Tumor
  11. Hypoxia and Proton microbeam: Role of Gap Junction Intercellular Communication in Inducing Bystander Responses on Human Lung Cancer Cells and Normal Cells
    Autsavapromporn N, Kobayashi A, Liu C, Jaikang C, Tengku Ahmad TA, Oikawa M, et al.
    Radiat Res, 2022 Feb 01;197(2):122-130.
    PMID: 34634126 DOI: 10.1667/RADE-21-00112.1
    Radiation-induced bystander effect (RIBE) has been identified as an important contributing factor to tumor resistance and normal tissue damage. However, the RIBE in cancer and normal cells under hypoxia remain unclear. In this study, confluent A549 cancer and WI-38 normal cells were subjected to condition of hypoxia or normoxia, before exposure to high-LET protons microbeam. After 6 h incubation, cells were harvested and assayed for colony formation, micronucleus formation, chromosome aberration and western blotting. Our results show that there were differences of RIBE in bystander A549 and WI-38 cells under hypoxia and normoxia. The differences were also observed in the roles of HIF-1α expression in bystander A549 and WI-38 cells under both conditions. Furthermore, inhibition of gap junction intercellular communication (GJIC) showed a decrease in toxicity of hypoxia-treated bystander A549 cells, but increased in bystander WI-38 cells. These findings clearly support that GJIC protection of bystander normal cells from toxicity while enhancing in bystander cancer cells. Together, the data show a promising strategy for high-LET radiation in designing an entire new line of drugs, either increase or restore GJIC in bystander cancer cells which in turn leads to enhancement of radiation accuracy for treatment of hypoxic tumors.
    Matched MeSH terms: Cell Line, Tumor
  12. Gold nanorod-assisted theranostic solution for nonvisible residual disease in bladder cancer
    Armanetti P, Locatelli I, Venegoni C, Alchera E, Campanella B, Pederzoli F, et al.
    Proc Natl Acad Sci U S A, 2024 Sep 10;121(37):e2411583121.
    PMID: 39236242 DOI: 10.1073/pnas.2411583121
    Residual nonvisible bladder cancer after proper treatment caused by technological and therapeutic limitations is responsible for tumor relapse and progression. This study aimed to demonstrate the feasibility of a solution for simultaneous detection and treatment of bladder cancer lesions smaller than one millimeter. The α5β1 integrin was identified as a specific marker in 81% of human high-grade nonmuscle invasive bladder cancers and used as a target for the delivery of targeted gold nanorods (GNRs). In a preclinical model of orthotopic bladder cancer expressing the α5β1 integrin, the photoacoustic imaging of targeted GNRs visualized lesions smaller than one millimeter, and their irradiation with continuous laser was used to induce GNR-assisted hyperthermia. Necrosis of the tumor mass, improved survival, and computational modeling were applied to demonstrate the efficacy and safety of this solution. Our study highlights the potential of the GNR-assisted theranostic strategy as a complementary solution in clinical practice to reduce the risk of nonvisible residual bladder cancer after current treatment. Further validation through clinical studies will support the findings of the present study.
    Matched MeSH terms: Cell Line, Tumor
  13. Fulltext Transcriptomic Analysis of the Anticancer Effects of Annatto Tocotrienol, Delta-Tocotrienol and Gamma-Tocotrienol on Chondrosarcoma Cells
    Pang KL, Foong LC, Abd Ghafar N, Soelaiman IN, Law JX, Leong LM, et al.
    Nutrients, 2022 Oct 13;14(20).
    PMID: 36296960 DOI: 10.3390/nu14204277
    Previous studies have demonstrated the anticancer activities of tocotrienol on several types of cancer, but its effects on chondrosarcoma have never been investigated. Therefore, this study aims to determine the anticancer properties of annatto tocotrienol (AnTT), γ-tocotrienol (γ-T3) and δ-tocotrienol (δ-T3) on human chondrosarcoma SW1353 cells. Firstly, the MTT assay was performed to determine the half-maximal inhibitory concentration (IC50) of tocotrienol on SW1353 cells after 24 h treatment. The mode of cell death, cell cycle analysis and microscopic observation of tocotrienol-treated SW1353 cells were then conducted according to the respective IC50 values. Subsequently, RNAs were isolated from tocotrienol-treated cells and subjected to RNA sequencing and transcriptomic analysis. Differentially expressed genes were identified and then verified with a quantitative PCR. The current study demonstrated that AnTT, γ-T3 and δ-T3 induced G1 arrest on SW1353 cells in the early phase of treatment (24 h) which progressed to apoptosis upon 48 h of treatment. Furthermore, tocotrienol-treated SW1353 cells also demonstrated large cytoplasmic vacuolation. The subsequent transcriptomic analysis revealed upregulated signalling pathways in endoplasmic reticulum stress, unfolded protein response, autophagy and transcription upon tocotrienol treatment. In addition, several cell proliferation and cancer-related pathways, such as Hippo signalling pathway and Wnt signalling pathway were also significantly downregulated upon treatment. In conclusion, AnTT, γ-T3 and δ-T3 possess promising anticancer properties against chondrosarcoma cells and further study is required to confirm their effectiveness as adjuvant therapy for chondrosarcoma.
    Matched MeSH terms: Cell Line, Tumor
  14. Fulltext Strobilanthes crispus elicits anti-tumor immunogenicity in in vitro and in vivo metastatic breast carcinoma
    Baraya YS, Wee CL, Mustapha Z, Wong KK, Yaacob NS
    PLoS One, 2022;17(8):e0271203.
    PMID: 35972917 DOI: 10.1371/journal.pone.0271203
    Plant-based anticancer agents have the potential to stimulate the immune system to act against cancer cells. A standardized bioactive subfraction of the Malaysian herb, Strobilanthes crispus (L.) Blume (S. crispus) termed F3, demonstrates strong anticancer effects in both in vitro and in vivo models. The anticancer effects might be attributable to its immunomodulatory properties as S. crispus has been traditionally used to enhance the immune system. The current study examined whether F3 could stimulate anti-tumorigenic immunogenicity against 4T1 cells in vitro and in 4T1 cell-induced mammary carcinoma mouse model. We observed that F3 induced significant increase in MHC class I and class II molecules. CD4+, CD8+ and IL-2+ (p<0.05 for all) cells infiltration was also significantly increased in the breast tumor microenvironment of F3-treated mice compared with the tumors of untreated mice. The number of CD68+ macrophages was significantly lower in F3-treated mice. We conclude that the antitumor and antimetastatic effects of S. crispus involve strong infiltration of T cells in breast cancer potentially through increased tumor antigen presentation via MHC proteins, as well as reduction of infiltrating tumor-associated macrophages.
    Matched MeSH terms: Cell Line, Tumor
  15. Inhibition of γ-secretase/Notch pathway as a potential therapy for reversing cancer drug resistance
    Feng M, Santhanam RK, Xing H, Zhou M, Jia H
    Biochem Pharmacol, 2024 Feb;220:115991.
    PMID: 38135129 DOI: 10.1016/j.bcp.2023.115991
    The mechanism of tumor drug resistance is complex and may involve stem cell maintenance, epithelial-mesenchymal transition, the activation of survival signaling pathways, transporter protein expression, and tumor microenvironment remodeling, all of which are linked to γ-secretase/Notch signaling. Increasing evidence has shown that the activation of the γ-secretase/Notch pathway is a key driver of cancer progression and drug resistance development and that γ-secretase inhibitors (GSIs) may be the most promising agents for reversing chemotherapy resistance of tumors by targeting the γ-secretase/Notch pathway. Here, we systematically summarize the roles in supporting γ-secretase/Notch activation-associated transformation of cancer cells into cancer stem cells, promotion of the EMT process, PI3K/Akt, MEK/ERK and NF-κB activation, enhancement of ABC transporter protein expression, and TME alteration in mediating tumor drug resistance. Subsequently, we analyze the mechanism of GSIs targeting the γ-secretase/Notch pathway to reverse tumor drug resistance and propose the outstanding advantages of GSIs in treating breast cancer drug resistance over other tumors. Finally, we emphasize that the development of GSIs for reversing tumor drug resistance is promising.
    Matched MeSH terms: Cell Line, Tumor
  16. Fulltext Rosiglitazone enhances the apoptotic effect of 5-fluorouracil in colorectal cancer cells with high-glucose-induced glutathione
    Lau MF, Chua KH, Sabaratnam V, Kuppusamy UR
    Sci Prog, 2020;103(1):36850419886448.
    PMID: 31795844 DOI: 10.1177/0036850419886448
    Colorectal cancer is one of the most prevalent noncommunicable diseases worldwide. 5-Fluorouracil is the mainstay of chemotherapy for colorectal cancer. Previously, we have demonstrated that high glucose diminishes the cytotoxicity of 5-fluorouracil by promoting cell cycle progression. The synergistic impact of rosiglitazone on 5-fluorouracil-induced apoptosis was further investigated in this study. Besides control cell lines (CCD-18Co), two human colonic carcinoma cell lines (HCT 116 and HT 29) were exposed to different treatments containing 5-fluorouracil, rosiglitazone or 5-fluorouracil/rosiglitazone combination under normal glucose (5.5 mM) and high-glucose (25 mM) conditions. The cellular oxidative stress level was evaluated with biomarkers of nitric oxide, advanced oxidation protein products, and reduced glutathione. The cell apoptosis was assessed using flow cytometry technique. High glucose caused the production of reduced glutathione in HCT 116 and HT 29 cells. Correspondingly, high glucose suppressed the apoptotic effect of 5-fluorouracil and rosiglitazone. As compared to 5-fluorouracil alone (2 µg/mL), addition of rosiglitazone significantly enhanced the apoptosis (increment rate of 5-20%) in a dose-dependent manner at normal glucose and high glucose levels. This study indicates that high-glucose-induced reduced glutathione confers resistance to apoptosis, but it can be overcome upon treatment of 5-fluorouracil and 5-fluorouracil/rosiglitazone combination. Rosiglitazone may be a promising antidiabetic drug to reduce the chemotherapeutic dose of 5-fluorouracil for colorectal cancer complicated with hyperglycemia.
    Matched MeSH terms: Cell Line, Tumor
  17. Targeted therapy of breast tumor by PLGA-based nanostructures: The versatile function in doxorubicin delivery
    Sonam Dongsar T, Tsering Dongsar T, Molugulu N, Annadurai S, Wahab S, Gupta N, et al.
    Environ Res, 2023 Sep 15;233:116455.
    PMID: 37356522 DOI: 10.1016/j.envres.2023.116455
    Breast carcinoma is a molecularly diverse illness, and it is among the most prominent and often reported malignancies in female across the globe. Surgical intervention, chemotherapy, immunotherapy, gene therapy, and endocrine treatment are among the currently viable treatment options for the carcinoma of breast. Chemotherapy is among the most prevalent cancer management strategy. Doxorubicin (DOX) widely employed as a cytostatic medication for the treatment of a variety of malignancies. Despite its widespread acceptance and excellent efficacy against an extensive line up of neoplasia, it has a variety of shortcomings that limit its therapeutic potential in the previously mentioned indications. Employment of nanoparticulate systems has come up as a unique chemo medication delivery strategy and are being considerably explored for the amelioration of breast carcinoma. Polylactic-co-glycolic acid (PLGA)-based nano systems are being utilized in a number of areas within the medical research and medication delivery constitutes one of the primary functions for PLGA given their inherent physiochemical attributes, including their aqueous solubility, biocompatibility, biodegradability, versatility in formulation, and limited toxicity. Herein along with the different application of PLGA-based nano formulations in cancer therapy, the present review intends to describe the various research investigations that have been conducted to enumerate the effectiveness of DOX-encapsulated PLGA nanoparticles (DOX-PLGA NPs) as a feasible treatment option for breast cancer.
    Matched MeSH terms: Cell Line, Tumor
  18. MALAT1: A key regulator in lung cancer pathogenesis and therapeutic targeting
    Bhat AA, Afzal O, Afzal M, Gupta G, Thapa R, Ali H, et al.
    Pathol Res Pract, 2024 Jan;253:154991.
    PMID: 38070223 DOI: 10.1016/j.prp.2023.154991
    Lung cancer remains a formidable global health burden, necessitating a comprehensive understanding of the underlying molecular mechanisms driving its progression. Recently, lncRNAs have become necessary controllers of various biological functions, including cancer development. MALAT1 has garnered significant attention due to its multifaceted role in lung cancer progression. Lung cancer, among other malignancies, upregulates MALAT1. Its overexpression has been associated with aggressive tumor behavior and poor patient prognosis. MALAT1 promotes cellular proliferation, epithelial-mesenchymal transition (EMT), and angiogenesis in lung cancer, collectively facilitating tumor growth and metastasis. Additionally, MALAT1 enhances cancer cell invasion by interacting with numerous signaling pathways. Furthermore, MALAT1 has been implicated in mediating drug resistance in lung cancer, contributing to the limited efficacy of conventional therapies. Recent advancements in molecular biology and high-throughput sequencing technologies have offered fresh perspectives into the regulatory networks of MALAT1 in lung cancer. It exerts its oncogenic effects by acting as a ceRNA to sponge microRNAs, thereby relieving their inhibitory effects on target genes. Moreover, MALAT1 also influences chromatin remodeling and post-translational modifications to modulate gene expression, further expanding its regulatory capabilities. This review sheds light on the multifaceted roles of MALAT1 in lung cancer progression, underscoring its potential as an innovative therapeutic target and diagnostic biomarker. Targeting MALAT1 alone or combined with existing therapies holds promise to mitigate lung cancer progression and improve patient outcomes.
    Matched MeSH terms: Cell Line, Tumor
  19. Fulltext Optimization of Pluchea indica (L.) leaf extract using ultrasound-assisted extraction and its cytotoxicity on the HT-29 colorectal cancer cell line
    Aishah Baharuddin S, Nadiah Abd Karim Shah N, Saiful Yazan L, Abd Rashed A, Kadota K, Al-Awaadh AM, et al.
    Ultrason Sonochem, 2023 Dec;101:106702.
    PMID: 38041881 DOI: 10.1016/j.ultsonch.2023.106702
    Colorectal cancer (CRC) is the most common malignancy and the third primary cause of cancer-related mortalities caused by unhealthy diet, hectic lifestyle, and genetic damage. People aged ≥ 50 are more at risk for CRC. Nowadays, bioactive compounds from plants have been widely studied in preventing CRC because of their anticancer and antioxidant properties. Herein, ultrasound-assisted extraction (UAE) was used to extract the bioactive compounds of Pluchea indica (L.) leaves. The resultant total phenolic content (TPC) and total flavonoid content (TFC) of P. indica (L.) leaves were analyzed using a response surface methodology (RSM). The central composite design was implemented to evaluate the amplitude (10 %-70 %) and treatment time (2-10 min) on both responses, i.e., TPC and TFC of P. indica (L.) leaves. The optimum UAE conditions were observed 40 % amplitude and 6 min of treatment, where the TPC and TFC were 3.26 ± 0.00 mg GAE/g d.w. and 67.58 ± 1.46 mg QE/g d.w., respectively. The optimum P. indica (L.) leaf extract was then screened for its cytotoxicity on the HT-29 colorectal cancer cell line. This extract had strong cytotoxicity with a half-maximal inhibitory concentration value (IC50) of 12 µg/mL. The phytochemical screening of bioactive compounds revealed that the optimal P. indica (L.) leaf extract contains flavonoids, namely, kaempferol 3-[2''',3''',5'''-triacetyl]-alpha-L-arabinofuranosyl-(1->6)-glucoside, myricetin 3-glucoside-7-galactoside, quercetin 3-(3''-sulfatoglucoside), and kaempferol 7,4'-dimethyl ether 3-O-sulfate, which could be good sources for promising anticancer agents. This study employs the RSM approach to utilize UAE for bioactive compounds extraction of P. indica (L.) leaves, identified the specific compounds present in the optimized extract and revealed its potential in preventing CRC.
    Matched MeSH terms: Cell Line
  20. Insights into the molecular mechanisms and signalling pathways of epithelial to mesenchymal transition (EMT) in colorectal cancer: A systematic review and bioinformatic analysis of gene expression
    Azizan S, Cheng KJ, Mejia Mohamed EH, Ibrahim K, Faruqu FN, Vellasamy KM, et al.
    Gene, 2024 Feb 20;896:148057.
    PMID: 38043836 DOI: 10.1016/j.gene.2023.148057
    Colorectal cancer (CRC) is ranked as the second leading cause of mortality worldwide, mainly due to metastasis. Epithelial to mesenchymal transition (EMT) is a complex cellular process that drives CRC metastasis, regulated by changes in EMT-associated gene expression. However, while numerous genes have been identified as EMT regulators through various in vivo and in vitro studies, little is known about the genes that are differentially expressed in CRC tumour tissue and their signalling pathway in regulating EMT. Using an integration of systematic search and bioinformatic analysis, gene expression profiles of CRC tumour tissues were compared to non-tumour adjacent tissues to identify differentially expressed genes (DEGs), followed by performing systematic review on common identified DEGs. Fifty-eight common DEGs were identified from the analysis of 82 tumour tissue samples obtained from four gene expression datasets (NCBI GEO). These DEGS were then systematically searched for their roles in modulating EMT in CRC based on previously published studies. Following this, 10 common DEGs (CXCL1, CXCL8, MMP1, MMP3, MMP7, TACSTD2, VIP, HPGD, ABCG2, CLCA4) were included in this study and subsequently subjected to further bioinformatic analysis. Their roles and functions in modulating EMT in CRC were discussed in this review. This study enhances our understanding of the molecular mechanisms underlying EMT and uncovers potential candidate genes and pathways that could be targeted in CRC.
    Matched MeSH terms: Cell Line, Tumor
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