Displaying publications 81 - 100 of 1033 in total

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  1. Fulltext The uS8, uS4, eS31, and uL14 Ribosomal Protein Genes Are Dysregulated in Nasopharyngeal Carcinoma Cell Lines
    Sim EU, Ng KL, Lee CW, Narayanan K
    Biomed Res Int, 2017;2017:4876954.
    PMID: 28791303 DOI: 10.1155/2017/4876954
    The association of ribosomal proteins with carcinogenesis of nasopharyngeal carcinoma (NPC) has been established in a limited subset of ribosomal protein genes. To date, three ribosomal protein genes, eL27 (L27), eL41 (L41), and eL43 (L37a), have been found to be differentially expressed in cell lines derived from NPC tumors. This raises the possibility of more ribosomal protein genes that could be associated with NPC. In this study, we investigated the expression profiles of eight ribosomal protein genes, uS8 (S8), uS4 (S9), eS31 (S27a), eL6 (L6), eL18 (L18), uL14 (L23), eL24 (L24), and eL30 (L30), in six NPC-derived cell lines (HONE-1, SUNE1, HK1, TW01, TW04, and C666-1). Their expression levels were compared with that of a nonmalignant nasopharyngeal epithelial cell line (NP69) using quantitative real-time PCR (RT-qPCR) assay. Of the eight genes studied, the expressions of four ribosomal protein genes uS8 (S8), uS4 (S9), eS31 (S27a), and uL14 (L23) were found to be significantly downregulated in NPC cell lines relative to NP69. Our findings provide novel empirical evidence of these four ribosomal protein genes as NPC-associated genetic factors and reinforce the relevance of ribosomal proteins in the carcinogenesis of nasopharyngeal cancer.
    Matched MeSH terms: Cell Line, Tumor
  2. Fulltext Synthesis and In Vitro Antiproliferative Activity of New 1-Phenyl-3-(4-(pyridin-3-yl)phenyl)urea Scaffold-Based Compounds
    Al-Sanea MM, Ali Khan MS, Abdelazem AZ, Lee SH, Mok PL, Gamal M, et al.
    Molecules, 2018 Jan 31;23(2).
    PMID: 29385071 DOI: 10.3390/molecules23020297
    A new series of 1-phenyl-3-(4-(pyridin-3-yl)phenyl)urea derivatives were synthesized and subjected to in vitro antiproliferative screening against National Cancer Institute (NCI)-60 human cancer cell lines of nine different cancer types. Fourteen compounds 5a-n were synthesized with three different solvent exposure moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure. Substituents with different π and σ values were added on the terminal phenyl group. Compounds 5a-e with a 4-hydroxymethylpiperidine moiety showed broad-spectrum antiproliferative activity with higher mean percentage inhibition values over the 60-cell line panel at 10 µM concentration. Compound 5a elicited lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose mode to determine median inhibitory concentration (IC50) values. The data revealed that urea compounds 5a and 5d are the most active derivatives, with significant efficacies and superior potencies than paclitaxel in 21 different cancer cell lines belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than gefitinib in 38 and 34 cancer cell lines, respectively, particularly colon cancer, breast cancer and melanoma cell lines.
    Matched MeSH terms: Cell Line, Tumor
  3. The evaluation expression of non-coding RNAs in response to HSV-G47∆ oncolytic virus infection in glioblastoma multiforme cancer stem cells
    Vazifehmand R, Ali DS, Othman Z, Chau DM, Stanslas J, Shafa M, et al.
    J Neurovirol, 2022 Dec;28(4-6):566-582.
    PMID: 35951174 DOI: 10.1007/s13365-022-01089-w
    Glioblastoma multiforme is the most aggressive astrocytes brain tumor. Glioblastoma cancer stem cells and hypoxia conditions are well-known major obstacles in treatment. Studies have revealed that non-coding RNAs serve a critical role in glioblastoma progression, invasion, and resistance to chemo-radiotherapy. The present study examined the expression levels of microRNAs (in normoxic condition) and long non-coding RNAs (in normoxic and hypoxic conditions) in glioblastoma stem cells treated with the HSV-G47∆. The expression levels of 43 miRNAs and 8 lncRNAs isolated from U251-GBM-CSCs were analyzed using a miRCURY LNA custom PCR array and a quantitative PCR assay, respectively. The data revealed that out of 43 miRNAs that only were checked in normoxic condition, the only 8 miRNAs, including miR-7-1, miR-let-7b, miR-130a, miR-137, miR-200b, miR-221, miR-222, and miR-874, were markedly upregulated. The expression levels of lncRNAs, including LEF1 antisense RNA 1 (LEF1-AS1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), long intergenic non-protein coding RNA 470 (LINC00470), tumor suppressor candidate 7 (TUSC7), HOX transcript antisense RNA (HOTAIR), nuclear paraspeckle assembly transcript 1 (NEAT1), and X inactive specific transcript (XIST), were markedly downregulated in the hypoxic microenvironment, and H19-imprinted maternally expressed transcript (H19) was not observed to be dysregulated in this environment. Under normoxic conditions, LEF1-AS1, MALAT1, LINC00470, H19, HOTAIR, NEAT1, and XIST were downregulated and TUSC7 was not targeted by HSV-G47∆. Overall, the present data shows HSVG47Δ treatment deregulates non-coding RNA expression in GBM-CSC tumor microenvironments.
    Matched MeSH terms: Cell Line, Tumor
  4. Fulltext Invasion and Metastasis Suppression by Anti-Neonatal Nav1.5 Antibodies in Breast Cancer
    Sharudin NA, Murtadha Noor Din AH, Azahar II, Mohd Azlan M, Yaacob NS, Sarmiento ME, et al.
    Asian Pac J Cancer Prev, 2022 Sep 01;23(9):2953-2964.
    PMID: 36172657 DOI: 10.31557/APJCP.2022.23.9.2953
    BACKGROUND: Detectable neonatal Nav1.5 (nNav1.5) expression in tumour breast tissue positive for lymph node metastasis and triple-negative subtype serves as a valid tumour-associated antigen to target and prevent breast cancer invasion and metastasis. Therapeutic antibodies against tumour antigens have become the predominant class of new drugs in cancer therapy because of their fewer adverse effects and high specificity.

    OBJECTIVE: This study was designed to investigate the therapeutic and anti-metastatic potential of the two newly obtained anti-nNav1.5 antibodies, polyclonal anti-nNav1.5 (pAb-nNav1.5) and monoclonal anti-nNav1.5 (mAb-nNav1.5), on breast cancer invasion and metastasis.

    METHODS: MDA-MB-231 and 4T1 cells were used as in vitro models to study the effect of pAb-nNav1.5 (59.2 µg/ml) and mAb-nNav1.5 (10 µg/ml) (24 hours treatment) on cell invasion. 4T1-induced mammary tumours in BALB/c female mice were used as an in vivo model to study the effect of a single dose of intravenous pAb-nNav1.5 (1 mg/ml) and mAb-nNav1.5 (1 mg/ml) on the occurrence of metastasis. Real-time PCR and immunofluorescence staining were conducted to assess the effect of antibody treatment on nNav1.5 mRNA and protein expression, respectively. The animals' body weight, organs, lesions, and tumour mass were also measured and compared.

    RESULTS: pAb-nNav1.5 and mAb-nNav1.5 treatments effectively suppressed the invasion of MDA-MB-231 and 4T1 cells in the 3D spheroid invasion assay. Both antibodies significantly reduced nNav1.5 gene and protein expression in these cell lines. Treatment with pAb-nNav1.5 and mAb-nNav1.5 successfully reduced mammary tumour tissue size and mass and prevented lesions in vital organs of the mammary tumour animal model whilst maintaining the animal's healthy weight. mRNA expression of nNav1.5 in mammary tumour tissues was only reduced by mAb-nNav1.5.

    CONCLUSION: Overall, this work verifies the uniqueness of targeting nNav1.5 in breast cancer invasion and metastasis prevention, but more importantly, humanised versions of mAb-nNav1.5 may be valuable passive immunotherapeutic agents to target nNav1.5 in breast cancer.

    Matched MeSH terms: Cell Line, Tumor
  5. Structural and functional insight into thiazolidinone derivatives as novel candidates for anticancer drug design: in vitro biological and in-silico strategies
    Channar PA, Aziz M, Ejaz SA, Chaudhry GE, Saeed A, Ujan R, et al.
    J Biomol Struct Dyn, 2023 Feb;41(3):942-953.
    PMID: 34927557 DOI: 10.1080/07391102.2021.2018045
    The compounds 2a-2h containing a thiazolidinone pharmacophore were synthesized via hetrerocylization of thiosemicarbazones with dimethyl acetylenedicarboxylate. The hybrid molecules were evaluated for anticancer activity against the human cell lines MCF-7, T47D (human breast adenocarcinoma) and HeLa (cervical cancer). Compounds 2c showed effective cytotoxicity on MCF-7 and HeLa (GI50 6.40 ± 0.10 μM/mL and GI5010.30 ± 1.09 μM/mL), and compound 2d also showed effective cytotoxicity against MCF-7 and HeLa cell lines i.e., (GI50 16.60 ± 0.21 μM/mL and GI50 15.02 ± 0.14 μM/mL). These findings were comparable to cisplatin (azane;dichloroplatinum) the standard drug (GI50 13.20 ± μM/mL and 15.10 μM/mL respectively) and consequently nominated for determination of the mode of cell death. The results revealed the cytotoxic effects of 2c and 2d by induction of apoptosis in MCF-7 and HeLa cell lines. Moreover the results were further supported by the Molecular Docking which predicts the binding interactions of the best anticancer ligands with Ribonucleotide reductase (RNR), which is essential enzyme required for de-novo synthesis of DNA precursors. Molecular dynamic simulations were also performed to determine the stability of protein-ligand complex under different simulated conditions. In addition, the computational studies including DFTs, ADMET properties suggested these compounds can act as lead molecules, for the synthesis of novel drug candidates for the treatment of specific cancer and its associated malignancies.
    Matched MeSH terms: Cell Line, Tumor
  6. Fulltext Synthesis of Bio-Inspired 1,3-Diarylpropene Derivatives via Heck Cross-Coupling and Cytotoxic Evaluation on Breast Cancer Cells
    Tan AS, Singh J, Rezali NS, Muhamad M, Nik Mohamed Kamal NNS, Six Y, et al.
    Molecules, 2022 Aug 23;27(17).
    PMID: 36080141 DOI: 10.3390/molecules27175373
    The Heck cross-coupling reaction is a well-established chemical tool for the synthesis of unsaturated compounds by formation of a new C-C bond. In this study, 1,3-diarylpropene derivatives, designed as structural analogues of stilbenoids and dihydrostilbenoids, were synthesised by the palladium-catalysed reactions of 2-amidoiodobenzene derivatives with either estragole or eugenol. The products were obtained with high (E) stereoselectivity but as two regioisomers. The ratios of isomers were found to be dependent on the nature of the allylbenzene partner and were rationalised by electronic effects exercising a determining influence in the β-hydride elimination step. In addition, the cytotoxic effects of all the Heck reaction products were evaluated against MCF-7 and MDA-MB-231 human breast cancer cells, with unpromising results. Among all, compound 7d exhibited weak cytotoxic activity towards MCF-7 cell lines with IC50 values of 47.92 µM in comparison with tamoxifen and was considered to have general toxicity (SI value < 2).
    Matched MeSH terms: Cell Line, Tumor
  7. Targeted delivery of paclitaxel drug using polymer-coated magnetic nanoparticles for fibrosarcoma therapy: in vitro and in vivo studies
    Al-Obaidy R, Haider AJ, Al-Musawi S, Arsad N
    Sci Rep, 2023 Feb 23;13(1):3180.
    PMID: 36823237 DOI: 10.1038/s41598-023-30221-x
    Fibrosarcoma is a rare type of cancer that affects cells known as fibroblasts that are malignant, locally recurring, and spreading tumor in fibrous tissue. In this work, an iron plate immersed in an aqueous solution of double added deionized water, supplemented with potassium permanganate solution (KMnO4) was carried out by the pulsed laser ablation in liquid method (PLAIL). Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using different laser wavelengths (1064, 532, and 266 nm) at a fluence of 28 J/cm2 with 100 shots of the iron plate to control the concentration, shape and size of the prepared high-stability SPIONs. The drug nanocarrier was synthesized by coating SPION with paclitaxel (PTX)-loaded chitosan (Cs) and polyethylene glycol (PEG). This nanosystem was functionalized by receptors that target folate (FA). The physiochemical characteristics of SPION@Cs-PTX-PEG-FA nanoparticles were evaluated and confirmed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-Ray diffraction (XRD), atomic force microscopy (AFM), and dynamic light scattering (DLS) methods. Cell internalization, cytotoxicity assay (MTT), apoptosis induction, and gene expression of SPION@Cs-PTX-PEG-FA were estimated in fibrosarcoma cell lines, respectively. In vivo studies used BALB/c tumor-bearing mice. The results showed that SPION@Cs-PTX-PEG-FA exhibited suitable physical stability, spherical shape, desirable size, and charge. SPION@Cs-PTX-PEG-FA inhibited proliferation and induced apoptosis of cancer cells (P tumor size compared to free PTX and control samples (P 
    Matched MeSH terms: Cell Line, Tumor
  8. Fulltext Phylattrin, a new cytotoxic xanthone from Calophyllum soulattri
    Mah SH, Ee GC, Teh SS, Rahmani M, Lim YM, Go R
    Molecules, 2012 Jul 10;17(7):8303-11.
    PMID: 22781442 DOI: 10.3390/molecules17078303
    Our continuing studies on secondary metabolites from the stem bark of Calophyllum soulattri has led to the isolation of another new diprenylated xanthone, phylattrin (1), in addition to five other xanthones and two common sterols. The xanthones are soulattrin (2), caloxanthone C (3), macluraxanthone (4), brasixanthone B (5) and trapezifolixanthone (6) while the sterols are stigmasterol (7) and β-sitosterol (8). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D-NMR, HRESIMS, IR and UV. Compounds 1-7 exhibited moderate cytotoxic activities against SNU-1, HeLa, Hep G2, NCI-H23, K562, Raji, LS174T, IMR-32 and SK-MEL-28 cells.
    Matched MeSH terms: Cell Line, Tumor
  9. Fulltext Antioxioxidant and antiapoptotic effects of Thymosin β4 in Aβ-induced SH-SY5Y cells via the 5-HTR1A/ERK axis
    Zhang GH, Chin KL, Yan SY, Pare R
    PLoS One, 2023;18(10):e0287817.
    PMID: 37788276 DOI: 10.1371/journal.pone.0287817
    Alzheimer's disease (AD) is a common amnestic cognitive impairment characterised by β-amyloid (Aβ) plaques deposit in the brain of the elderly. AD is a yet incurable disease due to its unknown exact pathogenesis and unavailability of effective remedies in clinical application. Thymosin β4 (Tβ4) is a housekeeping protein that plays important role in cell proliferation, migration and differentiation. It has the ability to protect and repair neurons however it is still unclear involvement in AD. Therefore, the aim of this study is to elucidate the role and mechanism of Tβ4 in mediating the improvement of AD. AD-like cell model was constructed in neuroblastoma cell line SH-SY5Y treated with Aβ. Overexpression of Tβ4 were done using lentivirus infection and downregulation through siRNA transfection. We performed western blot and flow cytometry to study the apoptosis and standard kits to measure the oxidative stress-associated biomarkers. There is significant increased in viability and decreased apoptosis in Tβ4 overexpression group compared to control. Furthermore, overexpression of Tβ4 suppressed the expression of pro-apoptotic markers such as Caspase-3, Caspase-8, and Bax meanwhile upregulated the expression of anti-apoptotic gene Bcl-2. Tβ4 alleviated oxidative damage by reducing MDA, LDH and ROS and increasing SOD and GSH-PX in Aβ-treated SH-SY5Y cells. We found that Tβ4 inhibit ERK/p38 MAPK pathway and intensify the expression of 5-HTR1A. Additionally, we showed that upregulation of 5-HTR1A dampened the Tβ4 to activate ERK signalling. In conclusion, our study revealed the neuroprotective role of Tβ4 in AD which may open up new therapeutic applications in AD treatment.
    Matched MeSH terms: Cell Line, Tumor
  10. Changes in the Proteome Profile of A549 Cells Following Helichrysetin-Induced Apoptosis Suggest the Involvement of DNA Damage Response and Cell Cycle Arrest-Associated Proteins
    Ho YF, Yajit NLM, Shiau JY, Malek SNA, Shyur LF, Karsani SA
    Appl Biochem Biotechnol, 2023 Nov;195(11):6867-6880.
    PMID: 36947367 DOI: 10.1007/s12010-023-04384-2
    Our previous findings demonstrated that Helichrysetin possessed promising anti-cancer activity. It was able to induce apoptosis in the A549 cell line. However, its mechanism of action is unknown. The present study aimed to unravel possible underlying molecular mechanisms of helichrysetin-induced apoptosis in A549 (human lung carcinoma) cells using comparative quantitative proteomics (iTRAQ labeled), followed by an exhaustive bioinformatics analysis. Our results suggested that DNA damage response (DDR) and cell cycle arrest were responsible for lung cancer cell death with helichrysetin treatment. Among proteins that changed in abundance were Nrf2 and HMOX1. They are oxidative stress-related proteins and were increased in abundance. BRAT1 was also increased in abundance, suggesting an increase in DNA damage repair, indicating the occurrence of DNA damage due to oxidative stress. However, several essential DDR downstream proteins such as p-ATM, BRCA1, FANCD2, and Rb1 that would further increase DNA damage were found to be dramatically decreased in relative abundance. Cell cycle-related proteins, p53, p21, and cyclin D1, were increased while cyclin A, cyclin E, and cdk2 were decreased. This is predicted to facilitate S-phase arrest. Furthermore, excessive DNA damage and prolonged arrest would in turn result in the induction of mitochondrial-mediated apoptosis. Based on these observations, we postulate that the effects of helichrysetin were in part via the suppression of DNA damage response which led to DNA damage and prolonged cell cycle arrest. Subsequently, this event initiated mitochondrial-mediated apoptosis in A549 lung cancer cells.
    Matched MeSH terms: Cell Line, Tumor
  11. Fulltext Radiosynthesis, Stability, Lipophilicity, and Cellular Uptake Evaluations of [131I]Iodine-α-Mangostin for Breast Cancer Diagnosis and Therapy
    Nurhidayah W, Widyasari EM, Daruwati I, Mahendra I, Subroto T, Khairul Ikram NK, et al.
    Int J Mol Sci, 2023 May 12;24(10).
    PMID: 37240025 DOI: 10.3390/ijms24108678
    The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [131I]Iodine-α-mangostin ([131I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [131I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including -20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [131I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [131I]I-AM has an RCP above 90% after three days of storage at -20 °C. A significant difference was obtained between [131I]I-AM uptake in T47D and Vero cells. Based on these results, [131I]I-AM has been prepared with high RCP, stable at -20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [131I]I-AM as a diagnostic and therapeutic agent for breast cancer.
    Matched MeSH terms: Cell Line, Tumor
  12. Therapeutic Potential of Albumin Nanoparticles Encapsulated Visnagin in MDA-MB-468 Triple-Negative Breast Cancer Cells
    Alsrhani A, Elderdery AY, Alzahrani B, Alzerwi NAN, Althobiti MM, Rayzah M, et al.
    Molecules, 2023 Apr 04;28(7).
    PMID: 37049991 DOI: 10.3390/molecules28073228
    Breast cancer is among the most recurrent malignancies, and its prevalence is rising. With only a few treatment options available, there is an immediate need to search for better alternatives. In this regard, nanotechnology has been applied to develop potential chemotherapeutic techniques, particularly for cancer therapy. Specifically, albumin-based nanoparticles are a developing platform for the administration of diverse chemotherapy drugs owing to their biocompatibility and non-toxicity. Visnagin, a naturally derived furanochromone, treats cancers, epilepsy, angina, coughs, and inflammatory illnesses. In the current study, the synthesis and characterization of albumin visnagin (AV) nanoparticles (NPs) using a variety of techniques such as transmission electron microscopy, UV-visible, Fourier transform infrared, energy dispersive X-ray composition analysis, field emission scanning electron microscopy, photoluminescence, X-Ray diffraction, and dynamic light scattering analyses have been carried out. The MTT test, dual AO/EB, DCFH-DA, Annexin-V-FITC/PI, Propidium iodide staining techniques as well as analysis of apoptotic proteins, antioxidant enzymes, and PI3K/Akt/mTOR signaling analysis was performed to examine the NPs' efficacy to suppress MDA-MB-468 cell lines. The NPs decreased cell viability increased the amount of ROS in the cells, disrupted membrane integrity, decreased the level of antioxidant enzymes, induced cell cycle arrest, and activated the PI3K/Akt/mTOR signaling cascade, ultimately leading to cell death. Thus, AV NPs possesses huge potential to be employed as a strong anticancer therapy alternative.
    Matched MeSH terms: Cell Line, Tumor
  13. Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy
    Lim YY, Zaidi AMA, Miskon A
    Molecules, 2023 Mar 24;28(7).
    PMID: 37049685 DOI: 10.3390/molecules28072920
    Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands' roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.
    Matched MeSH terms: Cell Line, Tumor
  14. Cluster of differentiation 147 (CD147) as potential membrane protein biomarker for bladder cancer cells
    Roslan A, Said DS, Sulaiman N, Mohd Ghani KA, Nurdin A
    J Pharm Biomed Anal, 2023 Nov 30;236:115729.
    PMID: 37778199 DOI: 10.1016/j.jpba.2023.115729
    Studies reveal that alterations in membrane protein (MP) patterns are associated with underlying drug resistance to chemotherapy. Therefore, the tryptic-digested MPs from the bladder cancer cell line were subjected to global proteomics using LC-MS/MS to identify the highly expressed potential MPs in bladder cancer cells. Our findings revealed the identification of MP biomarkers, CD147, and caveolin-1. Immunocytochemistry analysis confirmed the presence of CD147 on the cell membrane, while caveolin-1 showed positive signals without apparent staining on the membrane, suggesting its existence in multiple locations. Western blot analysis confirmed the higher expression of CD147 in non-invasive (RT 112) and metastatic (UM-UC-13) bladder cancer cells compared to invasive bladder cancer cells (5637 and J82), suggesting its potential as an MP biomarker for both of the former subtypes. The identified MPs could be used as drug therapy targets aimed at improving drug sensitivity and enhancing treatment outcomes in bladder cancer patients. SIGNIFICANCE: Identification of the membrane proteins associated with bladder cancer recurrence is crucial to understanding the mechanisms underlying the drug resistance to chemotherapy.
    Matched MeSH terms: Cell Line, Tumor
  15. Circular RNA ZNF800 (hsa_circ_0082096) regulates cancer stem cell properties and tumor growth in colorectal cancer
    Rengganaten V, Huang CJ, Wang ML, Chien Y, Tsai PH, Lan YT, et al.
    BMC Cancer, 2023 Nov 10;23(1):1088.
    PMID: 37950151 DOI: 10.1186/s12885-023-11571-1
    BACKGROUND: Cancer stem cells form a rare cell population in tumors that contributes to metastasis, recurrence and chemoresistance in cancer patients. Circular RNAs (circRNAs) are post-transcriptional regulators of gene expression that sponge targeted microRNA (miRNAs) to affect a multitude of downstream cellular processes. We previously showed in an expression profiling study that circZNF800 (hsa_circ_0082096) was up-regulated in cancer stem cell-enriched spheroids derived from colorectal cancer (CRC) cell lines.

    METHODS: Spheroids were generated in suspension spheroidal culture. The ZNF800 mRNA, pluripotency stem cell markers and circZNF800 levels were determined by quantitative RT-PCR. CircZNF800-miRNA interactions were shown in RNA pulldown assays and the miRNA levels determined by stem-loop qRT-PCR. The effects of circZNF800 on cell proliferation were tested by EdU staining followed by flowcytometry. Expression of stem cell markers CD44/CD133, Lgr5 and SOX9 was demonstrated in immunofluorescence microscopy. To manipulate the cellular levels of circZNF800, circZNF800 over-expression was achieved via transfection of in vitro synthesized and circularized circZNF800, and knockdown attained using a CRISPR-Cas13d-circZNF800 vector system. Xenografted nude mice were used to demonstrate effects of circZNF800 over-expression and knockdown on tumor growth in vivo.

    RESULTS: CircZNF800 was shown to be over-expressed in late-stage tumor tissues of CRC patients. Data showed that circZNF800 impeded expression of miR-140-3p, miR-382-5p and miR-579-3p while promoted the mRNA levels of ALK/ACVR1C, FZD3 and WNT5A targeted by the miRNAs, as supported by alignments of seed sequences between the circZNF800-miRNA, and miRNA-mRNA paired interactions. Analysis in CRC cells and biopsied tissues showed that circZNF800 positively regulated the expression of intestinal stem cell, pluripotency and cancer stem cell markers, and promoted CRC cell proliferation, spheroid and colony formation in vitro, all of which are cancer stem cell properties. In xenografted mice, circZNF800 over-expression promoted tumor growth, while circZNF800 knockdown via administration of CRISPR Cas13d-circZNF800 viral particles at the CRC tumor sites impeded tumor growth.

    CONCLUSIONS: CircZNF800 is an oncogenic factor that regulate cancer stem cell properties to lead colorectal tumorigenesis, and may be used as a predictive marker for tumor progression and the CRISPR Cas13d-circZNF800 knockdown strategy for therapeutic intervention of colorectal cancer.

    Matched MeSH terms: Cell Line, Tumor
  16. c(RGDfK) anchored surface manipulated liposome for tumor-targeted tyrosine kinase inhibitor (TKI) delivery to potentiate liver anticancer activity
    Deepak P, Kumar P, Arya DK, Pandey P, Kumar S, Parida BP, et al.
    Int J Pharm, 2023 Jul 25;642:123160.
    PMID: 37379892 DOI: 10.1016/j.ijpharm.2023.123160
    Current anticancer drug research includes tumor-targeted administration as a critical component because it is the best strategy to boost efficacy and decrease toxicity. Low drug concentration in cancer cells, nonspecific distribution, rapid clearance, multiple drug resistance, severe side effects, and other factors contribute to the disappointing results of traditional chemotherapy. As an innovative technique of treatments for hepatocellular carcinoma (HCC) in recent years, nanocarrier-mediated targeted drug delivery systems can overcome the aforesaid limitations via enhanced permeability and retention effect (EPR) and active targeting. Epidermal growth factor receptor (EGFR) inhibitor Gefitinib (Gefi) has dramatic effects on hepatocellular carcinoma. Herein, we developed and assessed an αvβ3 integrin receptor targeted c(RGDfK) surface modified liposomes for better targeting selectivity and therapeutic efficacy of Gefi on HCC cells. The conventional and modified Gefi loaded liposomes, i.e., denoted as Gefi-L and Gefi-c(RGDfK)-L, respectively, were prepared through the ethanol injection method and optimized via Box Behnken design (BBD). The FTIR and 1H NMR spectroscopy verified that the c(RGDfK) pentapeptides had formed an amide bond with the liposome surface. In addition, the particle size, Polydispersity index, zeta potential, encapsulation efficiency, and in-vitro Gefi release of the Gefi-L and Gefi-c(RGDfK)-L were measured and analyzed. As indicated by the MTT assay on HepG2 cells, Gefi-c(RGDfK)-L displayed considerably higher cytotoxicity than Gefi-L or Gefi alone. Throughout the incubation period, HepG2 cells took up significantly more Gefi-c(RGDfK)-L than Gefi-L. According to the in vivo biodistribution analysis, Gefi-c(RGDfK)-L accumulated more strongly at the tumor site than Gefi-L and free Gefi. Furthermore, HCC-bearing rats treated with Gefi-c(RGDfK)-L showed a substantial drop in liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, and total bilirubin levels) compared to the disease control group. Gefi-c(RGDfK)-L suppresses tumour growth more effectively than Gefi-L and free Gefi, according to an in vivo analysis of their anticancer activities. Thus, c(RGDfK)-surface modified liposomes, i.e., Gefi-c(RGDfK)-L may serve as an efficient carrier for the targeted delivery of anticancer drugs.
    Matched MeSH terms: Cell Line, Tumor
  17. Fulltext Epigenetic regulation of temozolomide resistance in human cancers with an emphasis on brain tumors: Function of non-coding RNAs
    Rezaee A, Tehrany PM, Tirabadi FJ, Sanadgol N, Karimi AS, Ajdari A, et al.
    Biomed Pharmacother, 2023 Sep;165:115187.
    PMID: 37499452 DOI: 10.1016/j.biopha.2023.115187
    Brain tumors, which are highly malignant, pose a significant threat to health and often result in substantial rates of mortality and morbidity worldwide. The brain cancer therapy has been challenging due to obstacles such as the BBB, which hinders effective delivery of therapeutic agents. Additionally, the emergence of drug resistance further complicates the management of brain tumors. TMZ is utilized in brain cancer removal, but resistance is a drawback. ncRNAs are implicated in various diseases, and their involvement in the cancer is particularly noteworthy. The focus of the current manuscript is to explore the involvement of ncRNAs in controlling drug resistance, specifically in the context of resistance to the chemotherapy drug TMZ. The review emphasizes the function of ncRNAs, particularly miRNAs, in modulating the growth and invasion of brain tumors, which significantly influences their response to TMZ treatment. Through their interactions with various molecular pathways, miRNAs are modulators of TMZ response. Similarly, lncRNAs also associate with molecular pathways and miRNAs, affecting the efficacy of TMZ chemotherapy. Given their functional properties, lncRNAs can either induce or suppress TMZ resistance in brain tumors. Furthermore, circRNAs, which are cancer controllers, regulate miRNAs by acting as sponges, thereby impacting the response to TMZ chemotherapy. The review explores the correlation between ncRNAs and TMZ chemotherapy, shedding light on the underlying molecular pathways involved in this process.
    Matched MeSH terms: Cell Line, Tumor
  18. Fulltext The anticancer mechanism of action of selected polyphenols in triple-negative breast cancer (TNBC)
    Farghadani R, Naidu R
    Biomed Pharmacother, 2023 Sep;165:115170.
    PMID: 37481930 DOI: 10.1016/j.biopha.2023.115170
    Breast cancer is a leadingcause of cancer-related deaths in women globally, with triple-negative breast cancer (TNBC) being an aggressive subtype that lacks targeted therapies and is associated with a poor prognosis. Polyphenols, naturally occurring compounds in plants, have been investigated as a potential therapeutic strategy for TNBC. This review provides an overview of the anticancer effects of polyphenols in TNBC and their mechanisms of action. Several polyphenols, including resveratrol, quercetin, kaempferol, genistein, epigallocatechin-3-gallate, apigenin, fisetin, hesperetin and luteolin, have been shown to inhibit TNBC cell proliferation, induce cell cycle arrest, promote apoptosis, and suppress migration/invasion in preclinical models. The molecular mechanisms underlying their anticancer effects involve the modulation of several signalling pathways, such as PI3K/Akt, MAPK, STATT, and NF-κB pathways. Polyphenols also exhibit synergistic effects with chemotherapy drugs, making them promising candidates for combination therapy. The review also highlights clinical trials investigating the potential use of polyphenols, individually or in combination therapy, against breast cancer. This review deepens the under-standing of the mechanism of action of respective polyphenols and provides valuable insights into the potential use of polyphenols as a therapeutic strategy for TNBC, and lays the groundwork for future research in this area.
    Matched MeSH terms: Cell Line, Tumor
  19. Fulltext Acquired radioresistance in EMT6 mouse mammary carcinoma cell line is mediated by CTLA-4 and PD-1 through JAK/STAT/PI3K pathway
    Sham NFR, Hasani NAH, Hasan N, Karim MKA, Fuad SBSA, Hasbullah HH, et al.
    Sci Rep, 2023 Feb 22;13(1):3108.
    PMID: 36813833 DOI: 10.1038/s41598-023-29925-x
    Cancer recurrence is often associated with the acquisition of radioresistance by cancer tissues due to failure in radiotherapy. The underlying mechanism leading to the development of acquired radioresistance in the EMT6 mouse mammary carcinoma cell line and the potential pathway involved was investigated by comparing differential gene expressions between parental and acquired radioresistance cells. EMT6 cell line was exposed to 2 Gy/per cycle of gamma-ray and the survival fraction between EMT6-treated and parental cells was compared. EMT6RR_MJI (acquired radioresistance) cells was developed after 8 cycles of fractionated irradiation. The development of EMT6RR_MJI cells was confirmed with further irradiation at different doses of gamma-ray, and both the survival fraction and migration rates were measured. Higher survival fraction and migration rates were obtained in EMT6RR_MJI cells after exposure to 4 Gy and 8 Gy gamma-ray irradiations compared to their parental cells. Gene expression between EMT6RR_MJI and parental cells was compared, and 16 genes identified to possess more than tenfold changes were selected and validated using RT-PCR. Out of these genes, 5 were significantly up-regulated i.e., IL-6, PDL-1, AXL, GAS6 and APCDD1. Based on pathway analysis software, the development of acquired radioresistance in EMT6RR_MJI was hypothesized through JAK/STAT/PI3K pathway. Presently, CTLA-4 and PD-1 were determined to be associated with JAK/STAT/PI3K pathway, where both their expressions were significantly increased in EMT6RR_MJI compared to parental cells in the 1st, 4th and 8th cycle of radiation. As a conclusion, the current findings provided a mechanistic platform for the development of acquired radioresistance in EMT6RR_MJI through overexpression of CTLA-4 and PD-1, and novel knowledge on therapeutic targets for recurrent radioresistant cancers.
    Matched MeSH terms: Cell Line, Tumor
  20. Fulltext Viral persistence in colorectal cancer cells infected by Newcastle disease virus
    Chia SL, Yusoff K, Shafee N
    Virol J, 2014 May 16;11:91.
    PMID: 24886301 DOI: 10.1186/1743-422X-11-91
    BACKGROUND: Newcastle disease virus (NDV), a single-stranded RNA virus of the family Paramyxoviridae, is a candidate virotherapy agent in cancer treatment. Promising responses were observed in clinical studies. Despite its high potential, the possibility of the virus to develop a persistent form of infection in cancer cells has not been investigated. Occurrence of persistent infection by NDV in cancer cells may cause the cells to be less susceptible to the virus killing. This would give rise to a population of cancer cells that remains viable and resistant to treatment.

    RESULTS: During infection experiment in a series of colorectal cancer cell lines, we adventitiously observed a development of persistent infection by NDV in SW480 cells, but not in other cell lines tested. This cell population, designated as SW480P, showed resistancy towards NDV killing in a re-infection experiment. The SW480P cells retained NDV genome and produced virus progeny with reduced plaque forming ability.

    CONCLUSION: These observations showed that NDV could develop persistent infection in cancer cells and this factor needs to be taken into consideration when using NDV in clinical settings.

    Matched MeSH terms: Cell Line, Tumor
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