Displaying publications 21 - 40 of 1718 in total

Abstract:
Sort:
  1. Vector-Mediated Cancer Gene Therapy Reduces Toxicity and Inhibition of Lung Carcinoma Growth in Nude Mice
    Khalaf AT, Wan J, Wei H, Fubing S, Zainol J, Kadir SYA, et al.
    Appl Biochem Biotechnol, 2024 Jan;196(1):261-274.
    PMID: 37119504 DOI: 10.1007/s12010-023-04463-4
    Replication-competent oncolytic adenovirus (TOA2) gene therapy is a recently introduced anti-tumor treatment regimen with superior results. The biodistribution studies of virus vector-based medicine seem more cautious and have been given much attention recently in terms of its quality and safety in preclinical trials. The current study determined the biodistribution and safety of a replication-competent adenovirus in different organs to predict its toxicity threshold. The present study has used TOA2, while biodistribution analysis was performed in human lung carcinoma A549-induced tumor-bearing nude mice model. Intratumoral injection was applied onto tumor-bearing mice with the adenovirus (3×1010 VP per mouse). Mice were sacrificed at the end of the experiment and the organs were dissected. Biodistribution analysis was done with complete hexon gene detection in each organ using quantitative real-time polymerase chain reaction (qRT-PCR). The biodistribution and concentration profiles showed that the TOA2 is well distributed in the entire tumor tissue. After dose 3 at day 11, the concentration of the virus has increased in the tumor tissue from 2240.54 (± 01.69) copies/100 ng genome to 13,120.28 (± 88.21) copies/100 ng genome on the 18th day, which eventually approached 336.45 (± 23.41) copies/100ng genome on the day 36. On the contrary, the concentration of the same decreased in the order of the liver, kidney, spleen, lung, and heart over time but no distributional traces in gonads. But the concentration found decreased dramatically in blood and other organs, while at the end of the experiment no detectable distribution was seen besides tumor tissue. The study confirms that adenovirus-based tumor therapy using conditionally replicating competent oncolytic TOA2 exhibited great efficiency with no toxicity at all.
    Matched MeSH terms: Cell Line, Tumor
  2. Fulltext Zerumbone-incorporated liquid crystalline nanoparticles inhibit proliferation and migration of non-small-cell lung cancer in vitro
    Manandhar B, Paudel KR, Clarence DD, De Rubis G, Madheswaran T, Panneerselvam J, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Jan;397(1):343-356.
    PMID: 37439806 DOI: 10.1007/s00210-023-02603-5
    Lung cancer is the second most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Zerumbone (ZER) is natural compound commonly found in the roots of Zingiber zerumbet which has recently demonstrated anti-cancer activity in both in vitro and in vivo studies. Despite their medical benefits, ZER has low aqueous solubility, poor GI absorption and oral bioavailability that hinders its effectiveness. Liquid crystalline nanoparticles (LCNs) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. This study aimed to formulate ZER-loaded LCNs and investigate their effectiveness against NSCLC in vitro using A549 lung cancer cells. ZER-LCNs, prepared in the study, inhibited the proliferation and migration of A549 cells. These inhibitory effects were superior to the effects of ZER alone at a concentration 10 times lower than that of free ZER, demonstrating a potent anti-cancer activity of ZER-LCNs. The underlying mechanisms of the anti-cancer effects by ZER-LCNs were associated with the transcriptional regulation of tumor suppressor genes P53 and PTEN, and metastasis-associated gene KRT18. The protein array data showed downregulation of several proliferation associated proteins such as AXL, HER1, PGRN, and BIRC5 and metastasis-associated proteins such as DKK1, CAPG, CTSS, CTSB, CTSD, and PLAU. This study provides evidence of potential for increasing the potency and effectiveness of ZER with LCN formulation and developing ZER-LCNs as a treatment strategy for mitigation and treatment of NSCLC.
    Matched MeSH terms: Cell Line, Tumor
  3. New dammarane-type triterpenoids from Aglaia elliptica (C.DC.) blume
    Farabi K, Harneti D, Darwati, Nurlelasari, Mayanti T, Maharani R, et al.
    Nat Prod Res, 2024;38(2):227-235.
    PMID: 35994369 DOI: 10.1080/14786419.2022.2114472
    Three new dammarane-type triterpenoids, namely elliptaglin A-C (1-3) were isolated from the stem bark of Aglaia elliptica (C.DC.) Blume along with three known derivatives, namely (20S)-hydroxydammar-24-en-3-on (4), cabralealactone (5), and E-25-hydroperoxydammar-23-en-20-ol-3-one (6). Subsequently, their chemical structures were determined using HR-ESI-MS, FTIR, 1D and 2D-NMR spectroscopic analysis as well as comparison with previous studies. The cytotoxicity activities of the isolated compounds against MCF-7 breast cancer and B16-F10 melanoma cell lines were then tested using PrestoBlue reagent. The analysis results showed that elliptaglin B (2) had the strongest activity against both cell lines with IC50 values of 60.98 and 51.83 µM, respectively.
    Matched MeSH terms: Cell Line, Tumor
  4. Phenolics and triterpenoids from stem bark of Calophyllum lanigerum var. austrocoriaceum (Whitmore) P. F. Stevens and their cytotoxic activities
    Mokhtar N, Karunakaran T, Santhanam R, Abu Bakar MH, Jong VYM
    Nat Prod Res, 2024;38(5):873-878.
    PMID: 37005001 DOI: 10.1080/14786419.2023.2196075
    Genus Calophyllum is well-known for its phenolic constituents, especially coumarins, which have shown to have a wide range of significant biological activities. In this study, four known phenolic constituents and two triterpenoids have been isolated from the stem bark of Calophyllum lanigerum. The compounds were two pyranochromanone acids are known as caloteysmannic acid (1), isocalolongic acid (2), a simple dihydroxyxanthone, namely euxanthone (3), one coumarin named calanone (4), and two common triterpenoids, friedelin (5), and stigmasterol (6). Chromanone acids were reported for the first time in this Calophyllum species. Cytotoxic evaluations were carried out on n-hexane extract (87.14 ± 2.04 µg/mL; 81.46 ± 2.42 µg/mL) followed by the chromanone acids (1 [79.96 ± 2.39 µM; 83.41 ± 3.39 µM] & 2 [57.88 ± 2.34; 53.04 ± 3.18 µM]) against two cancerous cell lines, MDA-MB-231 and MG-63 cell lines, respectively. The results showed that all tested samples exhibited moderate cytotoxicity.
    Matched MeSH terms: Cell Line
  5. Fulltext Synthesis and Characterization of Graphene Oxide/Polyethylene Glycol/Folic Acid/Brucine Nanocomposites and Their Anticancer Activity on HepG2 Cells
    Ibrahim IAA, Alzahrani AR, Alanazi IM, Shahzad N, Shahid I, Falemban AH, et al.
    Int J Nanomedicine, 2024;19:1109-1124.
    PMID: 38344441 DOI: 10.2147/IJN.S445206
    BACKGROUND: Liver cancer is the sixth most prevalent form of cancer and the second major cause of cancer-associated mortalities worldwide. Cancer nanotechnology has the ability to fundamentally alter cancer treatment, diagnosis, and detection.

    OBJECTIVE: In this study, we explained the development of graphene oxide/polyethylene glycol/folic acid/brucine nanocomposites (GO/PEG/Bru-FA NCs) and evaluated their antimicrobial and anticancer effect on the liver cancer HepG2 cells.

    METHODOLOGY: The GO/PEG/Bru-FA NCs were prepared using the co-precipitation technique and characterized using various techniques. The cytotoxicity of the GO/PEG/Bru-FA NCs was tested against both liver cancer HepG2 and non-malignant Vero cells using an MTT assay. The antimicrobial activity of the GO/PEG/Bru-FA NCs was tested against several pathogens using the well diffusion technique. The effects of GO/PEG/Bru-FA NCs on endogenous ROS accumulation, apoptosis, and MMP levels were examined using corresponding fluorescent staining assays, respectively. The apoptotic protein expressions, such as Bax, Bcl-2, and caspases, were studied using the corresponding kits.

    RESULTS: The findings of various characterization assays revealed the development of GO/PEG/Bru-FA NCs with face-centered spherical morphology and an agglomerated appearance with an average size of 197.40 nm. The GO/PEG/Bru-FA NCs treatment remarkably inhibited the growth of the tested pathogens. The findings of the MTT assay evidenced that the GO/PEG/Bru-FA NCs effectively reduced the HepG2 cell growth while not showing toxicity to the Vero cells. The findings of the fluorescent assay proved that the GO/PEG/Bru-FA NCs increased ROS generation, reduced MMP levels, and promoted apoptosis in the HepG2 cells. The levels of Bax, caspase-9, and -3 were increased, and Bcl-2 was reduced in the GO/PEG/Bru-FA NCs-treated HepG2 cells.

    CONCLUSION: The results of this work demonstrate that GO/PEG/Bru-FA NCs suppress viability and induce apoptosis in HepG2 cells, indicating their potential as an anticancer candidate.

    Matched MeSH terms: Cell Line, Tumor
  6. Synthesis, spectral characterisation, biocidal investigation, in-silico and molecular docking studies of 4-[(2-chloro-4-methylphenyl)carbamoyl]butanoic acid derived triorganotin(IV) compounds
    Hanifa B, Bibi N, Sirajuddin M, Tiekink ERT, Kubicki M, Khan I, et al.
    J Biomol Struct Dyn, 2024;42(4):1826-1845.
    PMID: 37114651 DOI: 10.1080/07391102.2023.2204160
    Three triorganotin(IV) compounds, R3Sn(L), with R = CH3 (1), n-C4H9 (2) and C6H5 (3), and LH = 4-[(2-chloro-4-methylphenyl)carbamoyl]butanoic acid, were prepared and confirmed by various techniques. A five-coordinate, distorted trigonal-bipyramidal geometry was elucidated for tin(IV) centres both in solution and solid states. An intercalation mode was confirmed for the compound SS-DNA interaction by UV-visible, viscometric techniques and molecular docking. MD simulation revealed stable binding of LH with SS-DNA. Anti-bacterial investigation revealed 2 to be generally the most potent, especially against Sa and Ab, i.e. having the lowest MIC values (≤0.25 μg/mL) compared to the standard anti-biotics vancomycin-HCl (MIC = 1 μg/mL) and colistin-sulphate (MIC = 0.25 μg/mL). Similarly, the anti-fungal profile shows 2 exhibits 100% inhibition against Ca and Cn fungal strains and has MIC values (≤0.25 μg/mL) comparatively lower than standard drug fluconazole (0.125 and 8 μg/mL for Ca and Cn, respectively). Compound 2 has the greatest activity with CC50 ≤ 25 μg/mL and HC50 > 32 μg/mL performed against HEC239 and RBC cell lines. The anti-cancer potential was assessed against the MG-U87 cell line, using cisplatin as the standard (133 µM), indicates 2 displays the greatest activity (IC50: 5.521 µM) at a 5 µM dose. The greatest anti-leishmanial potential was observed for 2 (87.75 at 1000 μg/mL) in comparison to amphotericin B (90.67). The biological assay correlates with the observed maximum of 89% scavenging activity exhibited by 2. The Swiss-ADME data publicised the screened compounds generally follow the rule of 5 of drug-likeness and have good bioavailability potential.
    Matched MeSH terms: Cell Line
  7. The Effects of Tiger Milk Mushroom Lignosus rhinocerus TM02® (Agaricomycetes) on Leukemogenicity Tyrosine Kinase Cell Lines
    Yahya TSANT, Azmi NC, Yee FS, Chyang PJ, Ting NS, Seng TC
    Int J Med Mushrooms, 2024;26(3):55-66.
    PMID: 38505903 DOI: 10.1615/IntJMedMushrooms.2024052325
    Leukemia can be a result of genetic changes associated with protein tyrosine kinase activity such as in MPL W515L and BCR/ABL genes. However, the current conventional treatment of leukemia produces severe side effects that urge the approach to use natural products. A medicinal mushroom, Lignosus rhinocerus shows potential as an anti-cancer treatment. To investigate the efficacy and mechanism of action of the L. rhinocerus cultivar (TM02®) extract on leukemogenic tyrosine kinase cell lines, a cold-water extract (CWE) was produced by using TM02® sclerotia powder at 4°C. The carbohydrate and protein contents were found to be 77.24% and 1.75% respectively. In comparison to the normal Ba/F3 cell, the CWE TM02® shows significant effects on exhibiting proliferation of Ba/F3 expressed MPL W515L and BCR/ABL, possibly due to the presence of phenolic compounds and antioxidant properties of TM02®, which contribute to act on various signaling pathways, and the reported apoptotic activity of CWE TM02®. In contrast, CWE TM02® significantly exhibited high scavenging activity of both Ba/F3 expressed MPL W515L and BCR/ABL. At concentrations of 125 μg/mL and 500 μg/mL of CWE TM02® decreased 49.5% and 67.5% of cell migration activity of Ba/F3 expressed MPL W515L and BCR/ABL respectively. Therefore, we postulate that CWE TM02® has the capability to mediate the migration route of the leukemogenic tyrosine kinase cell lines.
    Matched MeSH terms: Cell Line
  8. The Standardized Extract of Centella asiatica and Its Fractions Exert Antioxidative and Anti-Neuroinflammatory Effects on Microglial Cells and Regulate the Nrf2/HO-1 Signaling Pathway
    Hambali A, Jusril NA, Md Hashim NF, Abd Manan N, Adam SK, Mehat MZ, et al.
    J Alzheimers Dis, 2024;99(s1):S119-S138.
    PMID: 38250772 DOI: 10.3233/JAD-230875
    BACKGROUND: Neuroinflammation and oxidative stress can aggravate the progression of Alzheimer's disease (AD). Centella asiatica has been traditionally consumed for memory and cognition. The triterpenes (asiaticoside, madecassoside, asiatic acid, madecassic acid) have been standardized in the ethanolic extract of Centella asiatica (SECA). The bioactivity of the triterpenes in different solvent polarities of SECA is still unknown.

    OBJECTIVE: In this study, the antioxidative and anti-neuroinflammatory effects of SECA and its fractions were explored on lipopolysaccharides (LPS)-induced microglial cells.

    METHODS: HPLC measured the four triterpenes in SECA and its fractions. SECA and its fractions were tested for cytotoxicity on microglial cells using MTT assay. NO, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), ROS, and MDA (lipid peroxidation) produced by LPS-induced microglial cells were measured by colorimetric assays and ELISA. Nrf2 and HO-1 protein expressions were measured using western blotting.

    RESULTS: The SECA and its fractions were non-toxic to BV2 microglial cells at tested concentrations. The levels of NO, TNF-α, IL-6, ROS, and lipid peroxidation in LPS-induced BV2 microglial cells were significantly reduced (p 

    Matched MeSH terms: Cell Line
  9. Anticancer effect of aromatic isoniazid derivatives in human gastric adenocarcinoma cells
    Barathan M, Shivashekaregowda NKH, Hoong SM, Vellasamy KM, Vadivelu J
    Toxicol Appl Pharmacol, 2023 Dec 15;481:116767.
    PMID: 38007073 DOI: 10.1016/j.taap.2023.116767
    Current treatments for stomach cancer are often effective in curing cancer. However, these treatments can also have significant side effects, and they may not be effective in all cases. Hence synthetic compounds exhibit promise as potential agents for cancer treatment. In a previous study, we identified (E)-N'- (2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) as a novel antimycobacterial derivative of isoniazid with cytotoxic effects on the MCF-7 breast cancer cell line. This led us to investigate the potential anti-cancer properties of ITHB4 against adenocarcinoma gastric (AGS) cell line. The cytotoxic effect of ITHB4 has been determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and further confirmed for anticancer properties by means of apoptosis, reactive oxygen species (ROS), nuclear fragmentation, lactate dehydrogenase (LDH), caspases, cytokines and morphological including phenotypic changes of cells assay. The ITHB4 demonstrated a lower IC50 in inhibiting growth of AGS cells at 24 h compared to 48 and 72 h. ITHB4 has also shown no toxicity human immune cells. Treatment of ITHB4 against AGS for 24 h eventually lead to formation of early apoptotic AGS cells, reduced mitochondrial membrane potential, nuclear condensation, and nuclear fragmentation lastly increased in ROS levels together with the release of LDH, and secretion of caspases. The altered cytokine profile in ITHB4 treated AGS hints at the possibility that ITHB4 may possess anti-tumor and anti-inflammatory properties. Our results in this study demonstrate that ITHB4 has almost similar chemotherapeutic properties against gastric adenocarcinoma cells compared to breast cancer cell. This is suggesting that the anticancer capabilities of this compound should be in vivo and clinically assessed.
    Matched MeSH terms: Cell Line, Tumor
  10. Fulltext Berberine nanostructures attenuate ß-catenin, a key component of epithelial mesenchymal transition in lung adenocarcinoma
    Malyla V, De Rubis G, Paudel KR, Chellappan DK, Hansbro NG, Hansbro PM, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec;396(12):3595-3603.
    PMID: 37266589 DOI: 10.1007/s00210-023-02553-y
    Lung cancer (LC) is the leading cause of cancer-related deaths globally. It accounts for more than 1.9 million cases each year due to its complex and poorly understood molecular mechanisms that result in unregulated cell proliferation and metastasis. β-Catenin is a developmentally active protein that controls cell proliferation, metastasis, polarity and cell fate during homeostasis and aids in cancer progression via epithelial-mesenchymal transition. Therefore, inhibition of the β-catenin pathway could attenuate the progression of LC. Berberine, an isoquinoline alkaloid which is known for its anti-cancer and anti-inflammatory properties, demonstrates poor solubility and bioavailability. In our study, we have encapsulated berberine into liquid crystalline nanoparticles to improve its physiochemical functions and studied if these nanoparticles target the β-catenin pathway to inhibit the human lung adenocarcinoma cell line (A549) at both gene and protein levels. We observed for the first time that berberine liquid crystalline nanoparticles at 5 µM significantly attenuate the expression of the β-catenin gene and protein. The interaction between berberine and β-catenin was further validated by molecular simulation studies. Targeting β-catenin with berberine nanoparticles represents a promising strategy for the management of lung cancer progression.
    Matched MeSH terms: Cell Line, Tumor
  11. 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
  12. Fulltext CRNDE: A Pivotal Oncogenic Long Non-Coding RNA in Cancers
    Hor YZ, Salvamani S, Gunasekaran B, Yian KR
    Yale J Biol Med, 2023 Dec;96(4):511-526.
    PMID: 38161583 DOI: 10.59249/VHYE2306
    Colorectal Neoplasia Differentially Expressed (CRNDE), a long non-coding RNA that was initially identified as aberrantly expressed in colorectal cancer (CRC) has also been observed to exhibit elevated expression in various other human malignancies. Recent research has accumulated substantial evidence implicating CRNDE as an oncogenic player, exerting influence over critical cellular processes linked to cancer progression. Particularly, its regulatory interactions with microRNAs and proteins have been shown to modulate pathways that contribute to carcinogenesis and tumorigenesis. This review will comprehensively outline the roles of CRNDE in colorectal, liver, glioma, lung, cervical, gastric and prostate cancer, elucidating the mechanisms involved in modulating proliferation, apoptosis, migration, invasion, angiogenesis, and radio/chemoresistance. Furthermore, the review highlights CRNDE's potential as a multifaceted biomarker, owing to its presence in diverse biological samples and stable properties, thereby underscoring its diagnostic, therapeutic, and prognostic applications. This review aims to provide comprehensive insights of CRNDE-mediated oncogenesis and identify CRNDE as a promising target for future clinical interventions.
    Matched MeSH terms: Cell Line, Tumor
  13. 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
  14. 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
  15. 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
  16. New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis
    Sadrkhanloo M, Paskeh MDA, Hashemi M, Raesi R, Bahonar A, Nakhaee Z, et al.
    Pathol Res Pract, 2023 Nov;251:154902.
    PMID: 37922723 DOI: 10.1016/j.prp.2023.154902
    Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventional and current treatments fail to completely eradicate tumor cells, so new therapeutics targeting genes may be considered. PI3K/Akt is a regulator of events such as growth, cell death, migration, and differentiation, and its expression changes during cancer progression. PTEN reduces PI3K/Akt expression, and its mutations and depletions have been reported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and downregulation of PTEN in OS. Increasing PTEN expression may suppress PI3K/Akt to minimize tumorigenesis. In addition, PI3K/Akt shows a positive association with growth, metastasis, EMT and metabolism of OS cells and inhibits apoptosis. Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance.
    Matched MeSH terms: Cell Line, Tumor
  17. Fulltext High-throughput screening of ancient forest plant extracts shows cytotoxicity towards triple-negative breast cancer
    Li Y, Ling Ma N, Chen H, Zhong J, Zhang D, Peng W, et al.
    Environ Int, 2023 Nov;181:108279.
    PMID: 37924601 DOI: 10.1016/j.envint.2023.108279
    According to the World Health Organization, women's breast cancer is among the most common cancers with 7.8 million diagnosed cases during 2016-2020 and encompasses 15 % of all female cancer-related mortalities. These mortality events from triple-negative breast cancer are a significant health issue worldwide calling for a continuous search of bioactive compounds for better cancer treatments. Historically, plants are important sources for identifying such new bioactive chemicals for treatments. Here we use high-throughput screening and mass spectrometry analyses of extracts from 100 plant species collected in Chinese ancient forests to detect novel bioactive breast cancer phytochemicals. First, to study the effects on viability of the plant extracts, we used a MTT and CCK-8 cytotoxicity assay employing triple-negative breast cancer (TNBC) MDA-MB-231 and normal epithelial MCF-10A cell lines and cell cycle arrest to estimate apoptosis using flow cytometry for the most potent three speices. Based on these analyses, the final most potent extracts were from the Amur honeysuckle (Lonicera maackii) wood/root bark and Nigaki (Picrasma quassioides) wood/root bark. Then, 5 × 106 MDA-MB-231 cells were injected subcutaneously into the right hind leg of nude mice and a tumour was allowed to grow before treatment for seven days. Subsequently, the four exposed groups received gavage extracts from Amur honeysuckle and Nigaki (Amur honeysuckle wood distilled water, Amur honeysuckle root bark ethanol, Nigaki wood ethanol or Nigaki root bark distilled water/ethanol (1:1) extracts) in phosphate-buffered saline (PBS), while the control group received only PBS. The tumour weight of treated nude mice was reduced significantly by 60.5 % within 2 weeks, while on average killing 70 % of the MDA-MB-231 breast cancer cells after 48 h treatment (MTT test). In addition, screening of target genes using the Swiss Target Prediction, STITCH, STRING and NCBI-gene database showed that the four plant extracts possess desirable activity towards several known breast cancer genes. This reflects that the extracts may kill MBD-MB-231 breast cancer cells. This is the first screening of plant extracts with high efficiency in 2 decades, showing promising results for future development of novel cancer treatments.
    Matched MeSH terms: Cell Line, Tumor
  18. Selective pks+ Escherichia coli strains induce cell cycle arrest and apoptosis in colon cancer cell line
    Zulpa AK, Barathan M, Iyadorai T, Mariappan V, Vadivelu J, Teh CSJ, et al.
    World J Microbiol Biotechnol, 2023 Oct 06;39(12):333.
    PMID: 37801157 DOI: 10.1007/s11274-023-03767-1
    pks+ Escherichia coli (E. coli) triggers genomic instability in normal colon cells which leads to colorectal cancer (CRC) tumorigenesis. Previously, we reported a significant presentation of pks+ E. coli strains in CRC patients' biopsies as compared to healthy cohorts. In this work, using an in vitro infection model, we further explored the ability of these strains in modulating cell cycle arrest and activation of apoptotic mediators in both primary colon epithelial cells (PCE) and CRC cells (HCT-116). Sixteen strains, of which eight tumours and the matching non-malignant tissues, respectively, from eight pks+ E. coli CRC patients were subjected to BrDU staining and cell cycle analysis via flow cytometry, while a subset of these strains underwent analysis of apoptotic mediators including caspase proteins, cellular reactive oxygen species (cROS) and mitochondrial membrane potential (MMP) via spectrophotometry as well as proinflammatory cytokines via flow cytometry. Data revealed that all strains exerted S-phase cell cycle blockade in both cells and G2/M phase in PCE cells only. Moreover, more significant upregulation of Caspase 9, cROS, proinflammatory cytokines and prominent downregulation of MMP were detected in HCT-116 cells indicating the potential role of pks related bacterial toxin as anticancer agent as compared to PCE cells which undergo cellular senescence leading to cell death without apparent upregulation of apoptotic mediators. These findings suggest the existence of discrepancies underlying the mechanism of action of pks+ E. coli on both cancer and normal cell lines. This work propounds the rationale to further understand the mechanism underlying pks+ E. coli-mediated CRC tumorigenesis and cancer killing.
    Matched MeSH terms: Cell Line; Cell Line, Tumor
  19. Hyaluronic acid-functionalized lipoplexes and polyplexes as emerging nanocarriers for receptor-targeted cancer therapy
    Chandra J, Molugulu N, Annadurai S, Wahab S, Karwasra R, Singh S, et al.
    Environ Res, 2023 Sep 15;233:116506.
    PMID: 37369307 DOI: 10.1016/j.envres.2023.116506
    Cancer is an intricate disease that develops as a response to a combination of hereditary and environmental risk factors, which then result in a variety of changes to the genome. The cluster of differentiation (CD44) is a type of transmembrane glycoprotein that serves as a potential biomarker for cancer stem cells (CSC) and viable targets for therapeutic intervention in the context of cancer therapy. Hyaluronic acid (HA) is a linear polysaccharide that exhibits a notable affinity for the CD44 receptor. This characteristic renders it a promising candidate for therapeutic interventions aimed at selectively targeting CD44-positive cancer cells. Treating cancer via non-viral vector-based gene delivery has changed the notion of curing illness through the incorporation of therapeutic genes into the organism. The objective of this review is to provide an overview of various hyaluronic acid-modified lipoplexes and polyplexes as potential drug delivery methods for specific forms of cancer by effectively targeting CD44.
    Matched MeSH terms: Cell Line, Tumor
  20. 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
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links