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Fulltext Assessment of genotoxicity and cytotoxicity of standardized aqueous extract from leaves of Erythroxylum cuneatum in human HepG2 and WRL68 cells line

Wesam RK, Ghanya AN, Mizaton HH, Ilham M, Aishah A

Asian Pac J Trop Med, 2013 Oct;6(10):811-6.
PMID: 23870471 DOI: 10.1016/S1995-7645(13)60143-1

OBJECTIVE: To investigate the cytotoxicity and the genotoxicity of standardized aqueous of dry leaves of Erythroxylum cuneatum (E. cuneatum) in human HepG2 and WRL68 cells.
METHODS: The cytotoxicity of E. cuneatum extract was evaluated by both MTS and LDH assays. Genotoxicity study on E. cuneatum extract was assessed by the single cell gel electrophoresis (comet assay). The protective effect of E. cuneatum against menadione-induced cytotoxicity was also investigated.
RESULTS: Results from this study showed that E. cuneatum extract exhibited cytotoxic activities towards the cells with IC50 value of (125±12) and (125±14) μg/mL for HepG2 and WRL68 cells respectively, after 72 h incubation period as determined by MTS assay. LDH leakage was detected at (251±19) and (199.5±12.0) μg/mL for HepG2 and WRL68 respectively. Genotoxicity study results showed that treatment with E. cuneatum up to 1 mg/mL did not cause obvious DNA damage in WRL68 and HepG2 cells. Addition of E. cunaetum did not show significant protection towards menadione in WRL68 and HepG2 Cells.
CONCLUSIONS: E. cuneatum standardized aqueous extract might be developed in order to establish new pharmacological possibilities for its application.

Matched MeSH terms: Hep G2 Cells
Calophyllum inophyllum and Calophyllum soulattri source of anti-proliferative xanthones and their structure-activity relationships

Mah SH, Ee GC, Teh SS, Sukari MA

Nat Prod Res, 2015;29(1):98-101.
PMID: 25229947 DOI: 10.1080/14786419.2014.959949

Extensive chromatographic isolation and purification of the extracts of the stem bark of Calophyllum inophyllum and Calophyllum soulattri have resulted in 11 xanthones. C. inophyllum gave inophinnin (1), inophinone (2), pyranojacareubin (5), rheediaxanthone A (6), macluraxanthone (7) and 4-hydroxyxanthone (8), while C. soulattri afforded soulattrin (3), phylattrin (4), caloxanthone C (9), brasixanthone B (10) and trapezifolixanthone (11). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D NMR, GC-MS, IR and UV. Cytotoxicity screening (MTT assay) carried out in vitro on all the xanthones using five human cancer cell lines indicated good activities for some of these xanthones. The structure-activity relationship study revealed that the inhibitory activities exhibited by these xanthone derivatives to be closely related to the existence and nature of the pyrano and the prenyl substituent groups on their skeleton.

Matched MeSH terms: Hep G2 Cells
Cellular assessment of the extract of bambangan (Mangifera pajang) as a potential cytoprotective agent for the human hepatocellular HepG2 cell line

Abu Bakar MF, Mohamed M, Rahmat A, Burr SA, Fry JR

Food Chem, 2013 Jan 1;136(1):18-25.
PMID: 23017387 DOI: 10.1016/j.foodchem.2012.07.099

This study was conducted to investigate the potential of bambangan (Mangifera pajang) fruit extracts in the protection against oxidative damage caused by tert-butyl hydroperoxide in the human hepatocellular HepG2 cell line. Proteins which might be involved in the cytoprotective mechanism were investigated using western blotting technique. Quercetin was used as a positive control. The results showed that only the kernel extract of M. pajang and quercetin displayed cytoprotective activity in HepG2 cells, with EC(50) values of 1.2 and 5.3μg/ml, respectively. Expression of quinone reductase, glutathione reductase and methionine sulfoxide reductase A proteins were significantly up-regulated by quercetin, suggesting their involvement in the cytoprotective activity of quercetin. However, expressions of only glutathione reductase and methionine sulfoxide reductase A proteins were significantly up-regulated by the kernel extract, again suggesting their involvement in the cytoprotective activity of bambangan kernel extract. Future study is needed to investigate the involvement of other cytoprotective proteins in the cytoprotection mechanism.

Matched MeSH terms: Hep G2 Cells
Chalcones with electron-withdrawing and electron-donating substituents: anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis and regulation of apoptotic proteins

Mai CW, Yaeghoobi M, Abd-Rahman N, Kang YB, Pichika MR

Eur J Med Chem, 2014 Apr 22;77:378-87.
PMID: 24675137 DOI: 10.1016/j.ejmech.2014.03.002

In the present study, a series of 46 chalcones were synthesised and evaluated for antiproliferative activities against the human TRAIL-resistant breast (MCF-7, MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29), nasopharyngeal (CNE-1), erythromyeloblastoid (K-562) and T-lymphoblastoid (CEM-SS) cancer cells. The chalcone 38 containing an amino (-NH2) group on ring A was the most potent and selective against cancer cells. The effects of the chalcone 38 on regulation of 43 apoptosis-related markers in HT-29 cells were determined. The results showed that 20 apoptotic markers (Bad, Bax, Bcl-2, Bcl-w, Bid, Bim, CD40, Fas, HSP27, IGF-1, IGFBP-4, IGFBP-5, Livin, p21, Survivin, sTNF-R2, TRAIL-R2, XIAP, caspase-3 and caspase-8) were either up regulated or down regulated.

Matched MeSH terms: Hep G2 Cells
Characterization and biological properties of NanoCUR formulation and its effect on major human cytochrome P450 enzymes

Shamsi S, Chen Y, Lim LY

Int J Pharm, 2015 Nov 10;495(1):194-203.
PMID: 26319630 DOI: 10.1016/j.ijpharm.2015.08.066

Curcumin (CUR) has been formulated into a host of nano-sized formulations in a bid to improve its in vivo solubility, stability and bioavailability. The aim of this study was to investigate whether the encapsulation of CUR in nanocarriers would impede its biological interactivity, specifically its potential anti-cancer adjuvant activity via the modulation of CYP enzymes in vitro. NanoCUR, a micellar dispersion prepared via a thin film method using only Pluronic F127 as excipient, was amenable to lyophilization, and retained its nano-sized spherical dimensions (17-33 nm) upon reconstitution with water followed by dilution to 5 μM with HBSS or EMEM. NanoCUR was a weaker cytotoxic agent compared to CUR in solution (sCUR), affecting HepG2 cell viability only when the incubation time was prolonged from 4h to 48 h. Correlation with 2h uptake data suggests this was due to a lower cellular uptake rate of CUR from NanoCUR than from sCUR. The poorer CUR accessibility might also account for NanoCUR being a weaker inhibitor of CYP2C9 and CYP2D6 than sCUR. NanoCUR was, however, 1.76-fold more potent against the CYP3A4 (IC50 5.13 ± 0.91 μM) metabolic function. The higher activity against CYP3A4 might be attributed to the synergistic action of Pluronic F127, since the blank micellar dispersion also inhibited CYP3A4 activity. Both sCUR and NanoCUR had no effect on the CYP3A4 mRNA levels in the HepG2 cells. NanoCUR therefore, maintained most of the biological activities of CUR in vitro, albeit at a lower potency and response rate.

Matched MeSH terms: Hep G2 Cells
Fulltext Characterization and in vitro studies of the anticancer effect of oxidized carbon nanotubes functionalized with betulinic acid

Tan JM, Karthivashan G, Arulselvan P, Fakurazi S, Hussein MZ

Drug Des Devel Ther, 2014;8:2333-43.
PMID: 25429205 DOI: 10.2147/DDDT.S70650

Among the array of nanomaterials, carbon nanotubes have shown great potential as drug carriers in the field of nanomedicine, owing to their attractive physicochemical structure, which facilitates functionalization of therapeutic molecules onto their external walls or being encapsulated inside the tubes. The aim of this preliminary study was to formulate betulinic acid (BA), a poorly water-soluble drug, in oxidized multiwalled carbon nanotubes (MWCNT-COOH) for enhanced delivery efficiency into cancer cells with reduced cytotoxicity. The synthesized MWCNT-BA nanocomposite was characterized using ultraviolet-visible, Fourier transform infrared, thermogravimetric analysis, powder X-ray diffraction, and field emission scanning electron microscopy techniques. The loading of BA in MWCNT-COOH nanocarrier was estimated to be about 14.5%-14.8% (w/w), as determined by ultraviolet-visible and thermogravimetric analysis. Fourier transform infrared study shows that the peaks of the resulting MWCNT-BA nanocomposite correlate to the characteristic functional groups of BA and MWCNT-COOH. The powder X-ray diffraction results confirmed that the tubular structures of MWCNT-COOH were not affected by the drug loading mechanism of BA. The release profiles demonstrated that approximately 98% of BA could be released within 22 hours by phosphate-buffered saline solution at pH 7.4 compared with about 22% within 24 hours at pH 4.8. The biocompatibility studies revealed that MWCNT-BA at concentrations <50μg/mL expressed no cytotoxicity effects for mouse embryo fibroblast cells after 72 hours of treatment. The anticancer activity of MWCNT-BA was observed to be more sensitive to human lung cancer cell line when compared with human liver cancer cell line, with half maximal inhibitory concentration values of 2.7 and 11.0μg/mL, respectively. Our findings form a fundamental platform for further investigation of the MWCNT-BA formulation against different types of cancer cells.

Matched MeSH terms: Hep G2 Cells
Characterization of mutations in the FOXE1 gene in a cohort of unrelated Malaysian patients with congenital hypothyroidism and thyroid dysgenesis

Kang IN, Musa M, Harun F, Junit SM

Biochem Genet, 2010 Feb;48(1-2):141-51.
PMID: 20094846 DOI: 10.1007/s10528-009-9306-7

The FOXE1 gene was screened for mutations in a cohort of 34 unrelated patients with congenital hypothyroidism, 14 of whom had thyroid dysgenesis and 18 were normal (the thyroid status for 2 patients was unknown). The entire coding region of the FOXE1 gene was PCR-amplified, then analyzed using single-stranded conformational polymorphism, followed by confirmation by direct DNA sequencing. DNA sequencing analysis revealed a heterozygous A>G transition at nucleotide position 394 in one of the patients. The nucleotide transition changed asparagine to aspartate at codon 132 in the highly conserved region of the forkhead DNA binding domain of the FOXE1 gene. This mutation was not detected in a total of 104 normal healthy individuals screened. The binding ability of the mutant FOXE1 protein to the human thyroperoxidase (TPO) promoter was slightly reduced compared with the wild-type FOXE1. The mutation also caused a 5% loss of TPO transcriptional activity.

Matched MeSH terms: Hep G2 Cells
Cis-9, Trans-11 Conjugated Linoleic Acid Reduces Phosphoenolpyruvate Carboxykinase Expression and Hepatic Glucose Production in HepG2 Cells

Chai BK, Al-Shagga M, Pan Y, Then SM, Ting KN, Loh HS, et al.

Lipids, 2019 06;54(6-7):369-379.
PMID: 31124166 DOI: 10.1002/lipd.12154

Dysregulated hepatic gluconeogenesis is a hallmark of insulin resistance and type 2 diabetes mellitus (T2DM). Although existing drugs have been proven to improve gluconeogenesis, achieving this objective with functional food is of interest, especially using conjugated linoleic acid (CLA) found in dairy products. Both cis-9, trans-11 (c9,t11) and trans-10, cis-12 (t10,c12) isomers of CLA were tested in human (HepG2) and rat (H4IIE) hepatocytes for their potential effects on gluconeogenesis. The hepatocytes exposed for 24 h with 20 μM of c9,t11-CLA had attenuated the gluconeogenesis in both HepG2 and H4IIE by 62.5% and 80.1%, respectively. In contrast, t10,c12-CLA had no effect. Of note, in HepG2 cells, the exposure of c9,t11-CLA decreased the transcription of gluconeogenic enzymes, cytosolic phosphoenolpyruvate carboxykinase (PCK1) by 87.7%, and glucose-6-phosphatase catalytic subunit (G6PC) by 38.0%, while t10,c12-CLA increased the expression of G6PC, suggesting the isomer-specific effects of CLA on hepatic glucose production. In HepG2, the peroxisome proliferator-activated receptor (PPAR) agonist, rosiglitazone, reduced the glucose production by 72.9%. However, co-administration of c9,t11-CLA and rosiglitazone neither exacerbated nor attenuated the efficacy of rosiglitazone to inhibit glucose production; meanwhile, t10,c12-CLA abrogated the efficacy of rosiglitazone. Paradoxically, PPARγ antagonist GW 9662 also led to 70.2% reduction of glucose production and near undetectable PCK1 expression by abrogating CLA actions. Together, while the precise mechanisms by which CLA isomers modulate hepatic gluconeogenesis directly or via PPAR warrant further investigation, our findings establish that c9,t11-CLA suppresses gluconeogenesis by decreasing PEPCK on hepatocytes.

Matched MeSH terms: Hep G2 Cells
Clausenidin from Clausena excavata induces apoptosis in hepG2 cells via the mitochondrial pathway

Waziri PM, Abdullah R, Yeap SK, Omar AR, Abdul AB, Kassim NK, et al.

J Ethnopharmacol, 2016 Dec 24;194:549-558.
PMID: 27729282 DOI: 10.1016/j.jep.2016.10.030

ETHNOPHARMACOLOGICAL RELEVANCE: Clausena excavata Burm.f. is used locally in folk medicine for the treatment of cancer in South East Asia.
AIM OF THE STUDY: To determine the mechanism of action of pure clausenidin crystals in the induction of hepatocellular carcinoma (hepG2) cells apoptosis.
MATERIALS AND METHODS: Pure clausenidin was isolated from Clausena excavata Burm.f. and characterized using (1)H and (13)C NMR spectra. Clausenidin-induced cytotoxicity was determined by MTT assay. The morphology of hepG2 after treatment with clausenidin was determined by fluorescence and Scanning Electron Microscopy. The effect of clausenidin on the apoptotic genes and proteins were determined by real-time qPCR and protein array profiling, respectively. The involvement of the mitochondria in clausenidin-induced apoptosis was investigated using MMP, caspase 3 and 9 assays.
RESULTS: Clausenidin induced significant (p<0.05) and dose-dependent apoptosis of hepG2 cells. Cell cycle assay showed that clausenidin induced a G2/M phase arrest, caused mitochondrial membrane depolarization and significantly (p<0.05) increased expression of caspases 3 and 9, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, clausenidin caused decreased expression of the anti-apoptotic protein, Bcl 2 and increased expression of the pro-apoptotic protein, Bax. This finding was confirmed by the downregulation of Bcl-2 gene and upregulation of the Bax gene in the treated hepG2 cells.
CONCLUSION: Clausenidin extracted from Clausena excavata Burm.f. is an anti-hepG2 cell compound as shown by its ability to induce apoptosis through the mitochondrial pathway of apoptosis. Clausenidin can potentially be developed into an anticancer compound.

Matched MeSH terms: Hep G2 Cells
Fulltext Comparative proteomics reveals that YK51, a 4-Hydroxypandurantin-A analogue, downregulates the expression of proteins associated with dengue virus infection

Tan WL, Lee YK, Ho YF, Yusof R, Abdul Rahman N, Karsani SA

PeerJ, 2018;5:e3939.
PMID: 29404200 DOI: 10.7717/peerj.3939

Dengue is endemic throughout tropical and subtropical regions of the world. Currently, there is no clinically approved therapeutic drug available for this acute viral infection. Although the first dengue vaccine Dengvaxia has been approved for use in certain countries, it is limited to those without a previous dengue infection while the safety and efficacy of the vaccine in those elderly and younger children still need to be identified. Therefore, it is becoming increasingly important to develop therapeutics/drugs to combat dengue virus (DENV) infection. YK51 is a synthetic analogue of 4-Hydroxypandurantin A (a compound found in the crude extract of the rhizomes of Boesenbergia rotunda) that has been extensively studied by our research group. It has been shown to possess outstanding antiviral activity due to its inhibitory activity against NS2B/NS3 DENV2 protease. However, it is not known how YK51 affects the proteome of DENV infected cells. Therefore, we performed a comparative proteomics analysis to identify changes in protein expression in DENV infected HepG2 cells treated with YK51. Classical two-dimensional gel electrophoresis followed by protein identification using tandem mass spectrometry was employed in this study. Thirty proteins were found to be down-regulated with YK51 treatment. In silico analysis predicted that the down-regulation of eight of these proteins may inhibit viral infection. Our results suggested that apart from inhibiting the NS2B/NS3 DENV2 protease, YK51 may also be causing the down-regulation of a number of proteins that may be responsible in, and/or essential to virus infection. However, functional characterization of these proteins will be necessary before we can conclusively determine their roles in DENV infection.

Matched MeSH terms: Hep G2 Cells
Fulltext Construction and evaluation of V. cholerae O139 mutant, VCUSM21P, as a safe live attenuated cholera vaccine

Murugaiah C, Nik Mohd Noor NZ, Mustafa S, Manickam R, Pattabhiraman L

PLoS One, 2014;9(2):e81817.
PMID: 24505241 DOI: 10.1371/journal.pone.0081817

Cholera is a major infectious disease, affecting millions of lives annually. In endemic areas, implementation of vaccination strategy against cholera is vital. As the use of safer live vaccine that can induce protective immunity against Vibrio cholerae O139 infection is a promising approach for immunization, we have designed VCUSM21P, an oral cholera vaccine candidate, which has ctxA that encodes A subunit of ctx and mutated rtxA/C, ace and zot mutations. VCUSM21P was found not to disassemble the actin of HEp2 cells. It colonized the mice intestine approximately 1 log lower than that of the Wild Type (WT) strain obtained from Hospital Universiti Sains Malaysia. In the ileal loop assay, unlike WT challenge, 1×10⁶ and 1×10⁸ colony forming unit (CFU) of VCUSM21P was not reactogenic in non-immunized rabbits. Whereas, the reactogenicity caused by the WT in rabbits immunized with 1×10¹⁰ CFU of VCUSM21P was found to be reduced as evidenced by absence of fluid in loops administered with 1×10²-1×10⁷ CFU of WT. Oral immunization using 1×10¹⁰ CFU of VCUSM21P induced both IgA and IgG against Cholera Toxin (CT) and O139 lipopolysaccharides (LPS). The serum vibriocidal antibody titer had a peak rise of 2560 fold on week 4. Following Removable Intestinal Tie Adult Rabbit Diarrhoea (RITARD) experiment, the non-immunized rabbits were found not to be protected against lethal challenge with 1×10⁹ CFU WT, but 100% of immunized rabbits survived the challenge. In the past eleven years, V. cholerae O139 induced cholera has not been observed. However, attenuated VCUSM21P vaccine could be used for vaccination program against potentially fatal endemic or emerging cholera caused by V. cholerae O139.

Matched MeSH terms: Hep G2 Cells
Curcumin Modulates Hepatocellular Carcinoma by Reducing UNC119 Expression

Zhao Z, Malhotra A, Seng WY

J Environ Pathol Toxicol Oncol, 2019;38(3):195-203.
PMID: 31679307 DOI: 10.1615/JEnvironPatholToxicolOncol.2019029549

UNCI 19 expression has been reported to be significantly higher in hepatic cancer cells (HCC). However, the clinical significance of modulating UNC119 expression in HCC is not well understood. The study described here aimed to explore the potential of curcumin in modulation of UNC119 expression in HCC by assessment with quantitative real-time PCR, western blot, and immune-histochemical analyses in HCC cell lines and tissues. The biological functions of UNC119 in the proliferation, growth, and cycle of tumor cells were analyzed both in vitro and in vivo. UNC119 expression was upregulated in HCC cell lines and tissues as indicated by comparison with normal liver cells and tissues. Cellular function assays showed that higher levels of UNC119 not only promoted proliferation but also enhanced HCC cell migration and invasion. UNC119 promoted progression of the cell cycle and significantly promoted HCC cell growth through the Wnt/β-catenin signal pathway, and enhanced tumor migration and invasion by the TGF-β/EMT pathway. Curcumin efficiently inhibited HCC cell proliferation by blocking the Wnt/β-catenin pathway and inhabited migration and invasion by blocking the TGF-p/EMT signal pathway. Curcumin not only was beneficial for tumor remission but also contributed to the long-term survival of HCC-bearing mice. UNC119 was significantly upregulated and promoted cell growth in hepatic cancer cells and tissues by the Wnt/β-catenin signal pathway and migration by TGF-β/EMT signal pathway. Curcumin treatment inhibited cell proliferation, growth, migration, and invasion by inhibition of those pathways.

Matched MeSH terms: Hep G2 Cells
Fulltext Cytotoxic Effects of Pinnatane A Extracted from Walsura pinnata (Meliaceae) on Human Liver Cancer Cells

Zakaria N, Mahdzir MA, Yusoff M, Mohd Arshad N, Awang K, Nagoor NH

Molecules, 2018 Oct 23;23(11).
PMID: 30360475 DOI: 10.3390/molecules23112733

BACKGROUND: Pinnatane A from the bark of Walsura pinnata was investigated for its anti-cancer properties by analyzing the cytotoxic activities and cell cycle arrest mechanism induced in two different liver cancer cell lines.
METHODS: A 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to analyze the pinnatane A selectivity in inducing cell death in cancer and normal cells. Various biological assays were carried out to analyze the anti-cancer properties of pinnatane A, such as a live/dead assay for cell death microscopic visualization, cell cycle analysis using propidium iodide (PI) to identify the cell cycle arrest phase, annexin V-fluorescein isothiocyanate (annexin V-FITC)/PI flow cytometry assay to measure percentage of cell populations at different stages of apoptosis and necrosis, and DNA fragmentation assay to verify the late stage of apoptosis.
RESULTS: The MTT assay identified pinnatane A prominent dose- and time-dependent cytotoxicity effects in Hep3B and HepG2 cells, with minimal effect on normal cells. The live/dead assay showed significant cell death, while cell cycle analysis showed arrest at the G₀/G₁ phase in both cell lines. Annexin V-FITC/PI flow cytometry and DNA fragmentation assays identified apoptotic cell death in Hep3B and necrotic cell death in HepG2 cell lines.
CONCLUSIONS: Pinnatane A has the potential for further development as a chemotherapeutic agent prominently against human liver cells.

Matched MeSH terms: Hep G2 Cells
Cytotoxic and antioxidant effects of methoxylated stilbene analogues on HepG2 hepatoma and Chang liver cells: Implications for structure activity relationship

Hasiah AH, Ghazali AR, Weber JF, Velu S, Thomas NF, Inayat Hussain SH

Hum Exp Toxicol, 2011 Feb;30(2):138-44.
PMID: 20385705 DOI: 10.1177/0960327110368739

Stilbenes possess a variety of biological activities including chemopreventive activity. This study was conducted to evaluate the structural activity relationships of six methoxylated stilbene analogues with respect to their cytotoxic effects and antioxidant activities on HepG2 hepatoma and Chang liver cells. The cytotoxic and total antioxidant activities of six stilbene analogues were determined by MTT and Ferric Reducing Antioxidant Power (FRAP) assays, respectively. We found that the cis-methoxylated stilbene: (Z)-3,4,4'-trimethoxystilbene was the most potent and selective antiproliferative agent (IC₅₀ 89 µM) in HepG2 cells. For the total antioxidant activity, compounds possessing hydroxyl groups at the 4' position namely (E)-3-methoxy-4'-hydroxystilbene, (E)-3,5-dimethoxy-4'-hydroxystilbene (pterostilbene), (E)-4-methoxy-4'-hydroxystilbene showed the highest antioxidant activity. Structure activity relationship studies of these compounds demonstrated that the cytotoxic effect and antioxidant activities of the tested compounds in this study were structurally dependent.

Matched MeSH terms: Hep G2 Cells
Fulltext Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract

Namvar F, Rahman HS, Mohamad R, Baharara J, Mahdavi M, Amini E, et al.

Int J Nanomedicine, 2014;9:2479-88.
PMID: 24899805 DOI: 10.2147/IJN.S59661

Magnetic iron oxide nanoparticles (Fe3O4 MNPs) are among the most useful metal nanoparticles for multiple applications across a broad spectrum in the biomedical field, including the diagnosis and treatment of cancer. In previous work, we synthesized and characterized Fe3O4 MNPs using a simple, rapid, safe, efficient, one-step green method involving reduction of ferric chloride solution using brown seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and amino functional groups mainly relevant to polysaccharides, which acts as a potential stabilizer and metal reductant agent. The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4 MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa cells), and liver cancer (HepG2 cells). The cancer cells were treated with different concentrations of Fe3O4 MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity, resulting in an inhibitory concentration 50 (IC50) value of 23.83±1.1 μg/mL (HepG2), 18.75±2.1 μg/mL (MCF-7), 12.5±1.7 μg/mL (HeLa), and 6.4±2.3 μg/mL (Jurkat) 72 hours after treatment. Therefore, Jurkat cells were selected for further investigation. The representative dot plots from flow cytometric analysis of apoptosis showed that the percentages of cells in early apoptosis and late apoptosis were increased. Cell cycle analysis showed a significant increase in accumulation of Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9 in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4 MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer.

Matched MeSH terms: Hep G2 Cells
Cytotoxic effect of organotin(IV) benzylisopropyldithiocarbamate compounds on Chang liver cell and hepatocarcinoma HepG2 cell

Awang N, Kamaludin NF, Ghazali AR

Pak J Biol Sci, 2011 Aug 01;14(15):768-74.
PMID: 22303582

Cancer is one of the main causes of mortality and morbidity in world. New compounds are currently being synthesized to combat this disease. The organotins are gaining more attention as anti-cancer agents due to their potent cytotoxicity properties. In this study, a series of newly synthesized organotins namely dimethyltin (IV) (compound 1), dibutyltin (IV) (compound 2) and triphenyltin (IV) benzylisopropyldithiocarbamate (compound 3) were assessed for their cytotoxic activities against human Chang liver cells and hepatocarcinoma HepG2 cells. The cytotoxicity of these organotins in both cells upon 24 h treatment was assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Compound 2 and 3 exhibited potent cytotoxic activities towards both cells where the IC50 values were less then 10 microM. The IC50 value for compound 2 was 2.5 microM in Chang liver cells and 7.0 microM in HepG2 cells whereas compound 3 exhibited an IC50 value of 1.5 microM in Chang liver cells and 2.5 microM in HepG2 cells. Therefore, compound 2 and 3 were more toxic against human Chang liver cells as compared to hepatocarcinoma HepG2 cells. Interestingly, compound 1 did not have any IC50 value in both cells and hence can be classified as non-toxic. In conclusion, organotin (IV) benzylisopropyldithiocarbamate with insertion of dibutyl and triphenyl functional group possess potent cytotoxicity properties. Structural modification of these compounds can be carried out in further studies to produce less or non toxic effects towards normal human cell.

Matched MeSH terms: Hep G2 Cells/drug effects*
Fulltext Cytotoxicity anticancer activities of anastrozole against breast, liver hepatocellular, and prostate cancer cells

Hassan F, El-Hiti GA, Abd-Allateef M, Yousif E

Saudi Med J, 2017 Apr;38(4):359-365.
PMID: 28397941 DOI: 10.15537/smj.2017.4.17061

OBJECTIVES: To investigate the cytotoxic effect of anastrozole on breast (MCF7), liver hepatocellular (HepG2), and prostate (PC3) cancer cells. Methods: This is a prospective study. Anastrozole's mechanism of apoptosis in living cells was also determined by high content screening (HCS) assay. Methylthiazol tetrazolium (MTT) assay was carried out at the Centre of Biotechnology Research's, Al-Nahrain University, Baghdad, Iraq between July 2015 and October 2015. The HCS assay was performed at the Centre for Natural Product Research and Drug Discovery, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia between November 2015 and February 2016. Results: The most significant cytotoxic effect of anastrozole towards 3 cancer cell lines was obtained when its concentration was 400 µg/mL. The MCF7 cells were more sensitive to anastrozole compared with the HepG2 and PC-3 cells. There was a significant increase in membrane permeability, cytochrome c and nuclear intensity when anastrozole (200 µg/mL) was used compared with doxorubicin (20 µg/mL) as a standard. Also, there was a significant decrease in cell viability and mitochondrial membrane permeability when anastrozole (200 µg/mL) was used compared with positive control. Conclusion: Anastrozole showed cytotoxic effects against the MCF7, HepG2, and PC3 cell lines as determined in-vitro by the MTT assay. The HCS technique also showed toxic effect towards MCF7. It is evident that anastrozole inhibits the aromatase enzyme preventing the aromatization mechanism; however, it has a toxic effect.

Matched MeSH terms: Hep G2 Cells
Fulltext Cytotoxicity effect of degraded and undegraded kappa and iota carrageenan in human intestine and liver cell lines

Ariffin SH, Yeen WW, Abidin IZ, Abdul Wahab RM, Ariffin ZZ, Senafi S

BMC Complement Altern Med, 2014;14:508.
PMID: 25519220 DOI: 10.1186/1472-6882-14-508

Carrageenan is a linear sulphated polysaccharide extracted from red seaweed of the Rhodophyceae family. It has broad spectrum of applications in biomedical and biopharmaceutical field. In this study, we determined the cytotoxicity of degraded and undegraded carrageenan in human intestine (Caco-2; cancer and FHs 74 Int; normal) and liver (HepG2; cancer and Fa2N-4; normal) cell lines.

Matched MeSH terms: Hep G2 Cells
Fulltext Cytotoxicity effect of oil palm (Elaeis guineensis) kernel protein hydrolysates

Chang, S.K., Hamajima, H., Amin, I., Yanagita, T., Mohd. Esa, N., Baharuldin, M.T.H.

International Food Research Journal, 2014;21(3):909-914.
MyJurnal

This study was conducted to ascertain the cytotoxicity effect of oil palm (Elaeis guineensis) kernel protein hydrolysates (OPKHs) produced from its protein isolate. A modified microplate titer WST-1 [2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium] assay was used to investigate the cytotoxicity of hydrolysates produced from protease and pepsin-pancreatin hydrolysis at various concentrations (0.1, 1, 10, 100 μg/ml and 1 mg/ml) using HepG2 cell model. Additionally, peptide stimulation test using OPKHs at 1 mg/ml was carried out to investigate whether OPKHs could serve as growth factor for HepG2 cells other than affecting its viability. As a result, oleic acid appeared to normalize the WST-1 readings of HepG2 cells treated with both hydrolysates at 1 mg/ml. The presence of amino acids in OPKHs could stimulate the growth and prolongs the viability of HepG2 cells. Both OPKHs were non-cytotoxic to HepG2 cells at all tested concentrations even at high concentrations. This study indicated that pepsin-pancreatin and protease hydrolysates produced from oil palm kernel protein were non-cytotoxic on HepG2 cells.

Matched MeSH terms: Hep G2 Cells
Fulltext Delivery of chimeric hepatitis B core particles into liver cells

Lee KW, Tey BT, Ho KL, Tan WS

J Appl Microbiol, 2012 Jan;112(1):119-31.
PMID: 21992228 DOI: 10.1111/j.1365-2672.2011.05176.x

To display a liver-specific ligand on the hepatitis B virus core particles for cell-targeting delivery.

Matched MeSH terms: Hep G2 Cells

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