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Fulltext Aqueous fraction of Nephelium ramboutan-ake rind induces mitochondrial-mediated apoptosis in HT-29 human colorectal adenocarcinoma cells

Chan CK, Goh BH, Kamarudin MN, Kadir HA

Molecules, 2012 May 31;17(6):6633-57.
PMID: 22728359 DOI: 10.3390/molecules17066633

The aim of this study was to investigate the cytotoxic and apoptotic effects of Nephelium ramboutan-ake (pulasan) rind in selected human cancer cell lines. The crude ethanol extract and fractions (ethyl acetate and aqueous) of N. ramboutan-ake inhibited the growth of HT-29, HCT-116, MDA-MB-231, Ca Ski cells according to MTT assays. The N. ramboutan-ake aqueous fraction (NRAF) was found to exert the greatest cytotoxic effect against HT-29 in a dose-dependent manner. Evidence of apoptotic cell death was revealed by features such as chromatin condensation, nuclear fragmentation and apoptotic body formation. The result from a TUNEL assay strongly suggested that NRAF brings about DNA fragmentation in HT-29 cells. Phosphatidylserine (PS) externalization on the outer leaflet of plasma membranes was detected with annexin V-FITC/PI binding, confirming the early stage of apoptosis. The mitochondrial permeability transition is an important step in the induction of cellular apoptosis, and the results clearly suggested that NRAF led to collapse of mitochondrial transmembrane potential in HT-29 cells. This attenuation of mitochondrial membrane potential (Δψm) was accompanied by increased production of ROS and depletion of GSH, an increase of Bax protein expression, and induced-activation of caspase-3/7 and caspase-9. These combined results suggest that NRAF induces mitochondrial-mediated apoptosis.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Anticancer properties and phenolic contents of sequentially prepared extracts from different parts of selected medicinal plants indigenous to Malaysia

Ismail M, Bagalkotkar G, Iqbal S, Adamu HA

Molecules, 2012 May 14;17(5):5745-56.
PMID: 22628046 DOI: 10.3390/molecules17055745

Different parts of four edible medicinal plants (Casearia capitellata, Baccaurea motleyana, Phyllanthus pulcher and Strobilanthus crispus), indigenous to Malaysia, were extracted in different solvents, sequentially. The obtained 28 extracts were evaluated for their in vitro anticancer properties, using the MTS assay, on four human cancer cell lines: colon (HT-29), breast (MCF-7), prostate (DU-145) and lung (H460) cancers. The best anticancer activity was observed for the ethyl acetate (EA) extract of Casearia capitellata leaves on MCF-7 cell lines with IC₅₀ 2.0 μg/mL and its methanolic (MeOH) extract showed an outstanding activity against lung cancer cell lines. Dichloromethane (DCM) extract of Phyllanthus pulcher aerial parts showed the highest anticancer activity against DU-145 cell lines, while significant activity was exhibited by DCM extract of Phyllanthus pulcher roots on colon cancer cell lines with IC50 value of 8.1 μg/mL. Total phenolic content (TPC) ranged over 1-40 mg gallic acid equivalents (GAE)/g. For all the samples, highest yields of phenolics were obtained for MeOH extracts. Among all the extracts analyzed, the MeOH extracts of Strobilanthus crispus leaves exhibited the highest TPC than other samples (p < 0.05). This study shows that the nature of phenol determines its anticaner activity and not the number of phenols present.

Matched MeSH terms: Inhibitory Concentration 50
Dihydroquinazolin-4(1H)-one derivatives as novel and potential leads for diabetic management

Babatunde O, Hameed S, Salar U, Chigurupati S, Wadood A, Rehman AU, et al.

Mol Divers, 2021 Mar 01.
PMID: 33650031 DOI: 10.1007/s11030-021-10196-5

A variety of dihydroquinazolin-4(1H)-one derivatives (1-37) were synthesized via "one-pot" three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C-NMR. Compounds were subjected to α-amylase and α-glucosidase inhibitory activities. A number of derivatives exhibited significant to moderate inhibition potential against α-amylase (IC50 = 23.33 ± 0.02-88.65 ± 0.23 μM) and α-glucosidase (IC50 = 25.01 ± 0.12-89.99 ± 0.09 μM) enzymes, respectively. Results were compared with the standard acarbose (IC50 = 17.08 ± 0.07 μM for α-amylase and IC50 = 17.67 ± 0.09 μM for α-glucosidase). Structure-activity relationship (SAR) was rationalized by analyzing the substituents effects on inhibitory potential. Kinetic studies were implemented to find the mode of inhibition by compounds which revealed competitive inhibition for α-amylase and non-competitive inhibition for α-glucosidase. However, in silico study identified several important binding interactions of ligands (synthetic analogues) with the active site of both enzymes.

Matched MeSH terms: Inhibitory Concentration 50
Effects of Clitoria ternatea leaf extract on growth and morphogenesis of Aspergillus niger

Kamilla L, Mansor SM, Ramanathan S, Sasidharan S

Microsc Microanal, 2009 Aug;15(4):366-72.
PMID: 19575837 DOI: 10.1017/S1431927609090783

Clitoria ternatea is known for its antimicrobial activity but the antifungal effects of leaf extract on growth and morphogenesis of Aspergillus niger have not been observed. The extract showed a favorable antifungal activity against A. niger with a minimum inhibition concentration 0.8 mg/mL and minimum fungicidal concentration 1.6 mg/mL, respectively. The leaf extract exhibited considerable antifungal activity against filamentous fungi in a dose-dependent manner with 0.4 mg/mL IC50 value on hyphal growth of A. niger. The main changes observed under scanning electron microscopy after C. ternatea extract treatment were loss of cytoplasm in fungal hyphae and the hyphal wall and its diameter became markedly thinner, distorted, and resulted in cell wall disruption. In addition, conidiophore alterations were also observed when A. niger was treated with C. ternatea leaf extract.

Matched MeSH terms: Inhibitory Concentration 50
Functional Validation of DownRegulated MicroRNAs in HeLa Cells Treated with Polyalthia longifolia Leaf Extract Using Different Microscopic Approaches: A Morphological Alteration-Based Validation

Shanmugapriya, Vijayarathna S, Sasidharan S

Microsc Microanal, 2019 10;25(5):1263-1272.
PMID: 31383043 DOI: 10.1017/S1431927619014776

Several microscopy methods have been developed to assess the morphological changes in cells in the investigations of the mode of cell death in response to a stimulus. Our recent finding on the treatment of the IC50 concentration (26.67 μg/mL) of Polyalthia longifolia leaf extract indicated the induction of apoptotic cell death via the regulation of miRNA in HeLa cells. Hence, the current study was conducted to validate the function of these downregulated microRNAs in P. longifolia-treated HeLa cells using microscopic approaches. These include scanning electron microscope (SEM), transmission electron microscope (TEM), and acridine orange/propidium iodide (AO/PI)-based fluorescent microscopy techniques by observing the morphological alterations to cells after transfection with mimic miRNA. Interestingly, the morphological changes observed in this study demonstrated the apoptotic hallmarks, for instance, cell blebbing, cell shrinkage, cytoplasmic and nuclear condensation, vacuolization, cytoplasmic extrusion, and the formation of apoptotic bodies, which proved the role of dysregulated miRNAs in apoptotic HeLa cell death after treatment with the P. longifolia leaf extract. Conclusively, the current study proved the crucial role of downregulated miR-484 and miR-221-5p in the induction of apoptotic cell death in P. longifolia-treated HeLa cells using three approaches-SEM, TEM, and AO/PI-based fluorescent microscope.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Transcriptome Profiling of Toxoplasma gondii-Infected Human Cerebromicrovascular Endothelial Cell Response to Treatment with Monensin

Harun MSR, Taylor M, Zhu XQ, Elsheikha HM

Microorganisms, 2020 Jun 04;8(6).
PMID: 32512820 DOI: 10.3390/microorganisms8060842

Central to the progression of cerebral toxoplasmosis is the interaction of Toxoplasma gondii with the blood-brain barrier (BBB) endothelial cells. In the present work, we tested the hypothesis that inhibition of Wnt pathway signalling by the monovalent ionophore monensin reduces the growth of T. gondii infecting human brain microvascular endothelial cells (hBMECs) or microglial cells. The anti-parasitic effect of monensin (a Wnt signalling inhibitor) on the in vitro growth of T. gondii tachyzoites was investigated using two methods (Sulforhodamine B staining and microscopic parasite counting). The monensin inhibited T. gondii growth (50% inhibitory concentration [IC50] = 0.61 μM) with a selective index = 8.48 when tested against hBMECs (50% cytotoxic concentration [CC50] = 5.17 μM). However, IC50 of monensin was 4.13 μM with a SI = 13.82 when tested against microglia cells (CC50 = 57.08 μM), suggesting less sensitivity of microglia cells to monensin treatment. The effect of T. gondii on the integrity of the BBB was assessed by the transendothelial electrical resistance (TEER) assay using an in vitro human BBB model. The results showed that T. gondii infection significantly decreased hBMECs' TEER resistance, which was rescued when cells were treated with 0.1 µM monensin, probably due to the anti-parasitic activity of monensin. We also investigated the host-targeted effects of 0.1 µM monensin on global gene expression in hBMECs with or without T. gondii infection. Treatment of hBMECs with monensin did not significantly influence the expression of genes involved in the Wnt signalling pathway, suggesting that although inhibition of the Wnt signalling pathway did not play a significant role in T. gondii infection of hBMECs, monensin was still effective in limiting the growth of T. gondii. On the contrary, monensin treatment downregulated pathways related to steroids, cholesterol and protein biosynthesis and their transport between endoplasmic reticulum and Golgi apparatus, and deregulated pathways related to cell cycle and DNA synthesis and repair mechanisms. These results provide new insight into the host-modulatory effect of monensin during T. gondii infection, which merits further investigation.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext First report on a novel Nigrospora sphaerica isolated from Catharanthus roseus plant with anticarcinogenic properties

Ayob FW, Simarani K, Zainal Abidin N, Mohamad J

Microb Biotechnol, 2017 Jul;10(4):926-932.
PMID: 28612376 DOI: 10.1111/1751-7915.12603

This paper reports on the vinca alkaloid produced by a novel Nigrospora sphaerica isolated from Catharanthus roseus. Through liquid chromatography-mass spectrometry (LCMS), only the crude mycelia extract of this fungus was positive for determination of vinblastine. This vinca alkaloid was then purified by using high-performance liquid chromatography (HPLC) and tested for cytotoxicity activity using MTT assays. The breast cell line cancer (MDA-MB 231) was treated with a purified vinblastine which was intracellulary produced by N. sphaerica. The purified vinblastine from extracted leaf of C. roseus was used as a standard comparison. A positive result with a value of half maximal inhibitory concentration (IC50 ) of > 32 μg ml-1 was observed compared with standard (IC50 ) of 350 μg ml-1 only. It showed that a vinblastine produced by N. sphaerica has a high cytotoxicity activity even though the concentration of vinblastine produced by this endophytic fungus was only 0.868 μg ml-1 .

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Gamma-tocotrienol Alters Protein Expression of HepG2 Cell Line

Farahani, A.S.R., Zakiah, J., Abdul Rahman, M., Karsani, S.A., Wan, Ngah Wz

Medicine & Health, 2008;3(2):256-262.
MyJurnal

Gamma-tocotrienol (GTT) has been shown to exhibit significant antitumor activity in a variety of tumor cells. Previous findings have demonstrated that GTT had antiprolifera-tive effects on a liver cancer cell line (HepG2) with an IC50 value of 170μM. In this study, two dimensional gel electrophoresis (2DE) was used to determine changes in protein expression in HepG2 cell line following treatment with GTT. The ultimate aim is to identify the possible molecular mechanisms involved in GTT antitumor activity. This study is focused on obtaining a 2DE protein profile for HepG2 cell line with and without
GTT treatment. In the preliminary analysis of the resulting 2DE profiles, 18 protein spots were found to be differentially expressed in cells treated with GTT. This observa-tion is confirmed by extending the analysis to a larger sample size. By studying the effects of GTT treatment on differential protein expression in HepG2 cells the underly-ing mechanisms involved in the antitumor activity of GTT may be elucidated.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Effects of gelam honey on oxidative stress in lung cancer cells

Gunasekaran, G., Muhamad Fitri C.A., Chandrashegkar, S., Hajar Amalnina A.B., Raishan, S., Nurul Faiznani, Z., et al.

Medicine & Health, 2017;12(2):202-209.
MyJurnal

Madu gelam telah didapati mempunyai kesan anti-oksidatif, anti-kanser dan antiinflamasi
terhadap banyak jenis kanser. Tujuan kajian ini adalah untuk menentukan
kesan madu gelam terhadap aras tekanan oksidatif sel kanser peparu manusia.
IC50 madu gelam ditentukan dengan merawat sel A549 dengan dos madu yang
berbeza (50-200 mg/ml). Sel dibahagikan kepada 4 kumpulan dan diaruh tekanan
oksidatif dengan menggunakan hidrogen peroksida (H2
O2
) mengikut kumpulan
tertentu: kawalan, H2
O2
, madu gelam, H2
O2
+ madu gelam. Selepas 24 jam
rawatan, biopetanda tekanan oksidatif seperti malondialdehid (MDA) dan protein
karbonil ditentukan. Aruhan tekanan oksidatif meningkatkan aras MDA (p

Matched MeSH terms: Inhibitory Concentration 50
An efficient ionic liquid mediated synthesis, cholinesterase inhibitory activity and molecular modeling study of novel piperidone embedded α,β-unsaturated ketones

Kia Y, Osman H, Kumar RS, Murugaiyah V, Basiri A, Khaw KY, et al.

Med Chem, 2014;10(5):512-20.
PMID: 24138113

A series of hitherto unreported piperidone embedded α,β-unsaturated ketones were synthesized efficiently in ionic solvent and evaluated for cholinesterase inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Most of the synthesized compounds displayed good enzyme inhibition; therein compounds 7i and 7f displayed significant activity against AChE with IC50 values of 1.47 and 1.74 µM, respectively. Compound 6g showed the highest BChE inhibitory potency with IC50 value of 3.41 µM, being 5 times more potent than galanthamine. Molecular modeling simulation was performed using AChE and BChE receptors extracted from crystal structure of human AChE and human BChE to determine the amino acid residues involved in the binding interaction of synthesized compounds and their relevant receptors.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Mushrooms: a potential natural source of anti-inflammatory compounds for medical applications

Elsayed EA, El Enshasy H, Wadaan MA, Aziz R

Mediators Inflamm, 2014;2014:805841.
PMID: 25505823 DOI: 10.1155/2014/805841

For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Betulinic acid was more cytotoxic towards the human breast cancer cell line MDA-MB-231 than the human promyelocytic leukaemia cell line HL-60

Latifah Saiful Yazan, Faujan Ahmad, Ooi, Choong Li, Raha Abdul Rahim, Hisyam Abdul Hamid, Lee, Pei Sze

Malaysian Journal of Pharmaceutical Science, 2009;7(1):23-37.
MyJurnal

Betulinic acid (BA) is a pentacyclic triterpene found in several botanical sources that has been shown to cause apoptosis in a number of cell lines. This study was undertaken to determine the in vitro cytotoxic properties of BA towards the human mammary carcinoma cell line MDA-MB-231 and the human promyelocytic leukaemia cell line HL-60 and the mode of the induced cell death. The cytotoxicity and mode of cell death of BA were determined using the MTT assay and DNA fragmentation analysis, respectively. In our study, the compound was found to be cytotoxic to MDA-MB-231 and HL-60 cells with IC50 values of 58 μg/mL and 134 μg/mL, respectively. Cells treated with high concentrations of BA exhibited features characteristic of apoptosis such as blebbing, shrinking and a number of small cytoplasm body masses when viewed under an inverted light microscope after 24h. The incidence of apoptosis in MDA-MB-231 was further confirmed by the DNA fragmentation analysis, with the formation of DNA fragments of oligonucleosomal size (180-200 base pairs), giving a ladder-like pattern on agarose gel electrophoresis. BA was more cytotoxic towards MDA-MB-231 than HL-60 cells, and induced apoptosis in MDA-MB-231 cells.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Anti-proliferation effects of benzimidazole analogues on gastric cancer: structure analysis relationship

Wan Mohd Ikhtiaruddin, Abdah Md Akim, Hasiah Ab Hamid, Norhaizan Mohd Esa, Norizan Ahmat

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):50-50.
MyJurnal

Introduction: Benzimidazole analogues are bicyclic compounds that had been synthesized comprising the fusion of benzene and imidazole. It gains interest in research as it poses numerous therapeutic potential such as anti-ulcer, anti-malarial, anti-helminthic, anti-fungal, anti-inflammatory, and anti-cancer. Hence, this work aims to screen novel benzimidazole analogues using MTT assay for potential anti-proliferation activities on gastric cancer, which is the second cause of cancer-related death. Methods: MTT assay was conducted following standard protocol on HGT-1 gastric cancer cells. Cells were seeded and allowed to attach overnight before being introduced with various con-centration of benzimidazole analogues up to 72 hours and the optical density of the MTT was recorded using 560 nm wavelength. Two-Way ANOVA was used to analyse all data, followed by post-hoc Tukey test and the structure analysis relationship was analysed using MTT result. Results: From five analogues, only compound 4 showed an-ti-proliferation activity with IC50 8.212 ± 0.813 μM at 72 hours. Compound 4 had hydroxyl group at ortho- and para- position and remarkably, compound 2 which contained the hydroxyl group at ortho- and meta- position together with compound 5 which contained the combination of meta- and para- induced proliferation on gastric cancer. Conclusion: Different position of hydroxyl group on the benzene ring gives different activities on gastric cancer and from the experiment, only compound 4 had the anti-proliferative activity.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Determinations of secondary metabolites and its antioxidant activities of various fractions of Albizia myriophylla Bark and evaluations of anti-obesity effect of methanolic extract of Albizia myriophylla in high-fat diet mice

Goh Yong Meng, Mahdi Ebrahimi, Nurmawati Syakroni, Mohammad Fasakh Jahroumi, Tarlan Jaafarpour, Azmah Saat

Malaysian Journal of Medicine and Health Sciences, 2019;15(107):5-5.
MyJurnal

Introduction: This study examined the antioxidant activity and phenolic, flavonoid and saponin contents from mul-tiple solvent extracts of Albizia myriophylla (ABZ) bark. Antioxidant activity of the methanol extract and its derived fractions namely hexane, chloroform, ethyl acetate, butanol and a residual aqueous fraction of the bark of ABZ was assessed. Methods: All the extracts showed a significant presence of phenolic, flavonoids and saponins. In DPPH (1, 1-diphenyl-2-picrylhidrazyl) radical scavenging test, ABTS (2-2’-azinobis 3-ethyl-6-sulfonic acid) radical scavenging test and reducing activity on ferrous iron (FRAP) test, the total antioxidant capacity was found to be varied in different fractions. Results: The IC50 calculated value of the three assays showed that the methanolic extract of ABZ bark had the lowest IC50 value for each assay, compared to the other extracts signifying highest anti-oxidant activity. Methan-olic extract of ABZ was tested in high-fat diet induced mice, which showed reduce adipocyte cellularity and reduces the cholesterol, triglyceride, LDL level while increasing the HDL level. Conclusion: The antioxidant capacity with probable free radical scavenging activity of the methanolic extract of ABZ may be useful for the treatment of chronic inflammatory-related metabolic diseases such as obesity.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Synthesis, characterization and biological properties of copper(II) and zinc(II) complexes against blood-stage Plasmodium falciparum

Lai, Jing-Wei, Ng, Chew-Hee, Lim, Yvonne Ai-Lian, Mohd Jamil Maah

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):1-1.
MyJurnal

Introduction: The spread of multidrug-resistant malaria parasite – Plasmodium sp. to commercially available antimalarial drugs, i.e. artemisinin-based combination therapies (ACTs) and chloroquine (CQ), has become a global treat to eliminate malaria. To limit the impact of antimalarial drug resistance, a new potent and affordable alternative is urgently needed. A number of metal-based compounds (metallodrugs) have been found active against Plasmodium falciparum, the species that causes potentially fatal cerebral malaria, as they are ease in ligand grafting of multi-functional groups. Ferroquine (FQ) is one of the metalloantimalarial drugs that is currently undergoing clinical trials. Methods: In this study, a series of ternary copper(II) and zinc(II) complexes – Cu(phen)(edda) 1, Zn(phen)(edda) 2, [Cu(phen)(cdmg)] NO3 3 and [Zn(phen)(c-dmg)]NO3 4 were synthesized and characterized by the following tests: Fourier transformed infrared (FTIR), CHN elemental analysis, UV-Vis spectroscopy, molar conductivity and magnetic susceptibility measurements. Results: In vitro hemolytic and antimalarial assays using SYBR Green I dye were done to determine the biological properties of these complexes. Preliminary biological evaluation demonstrated that all the complexes 1, 2, 3 and 4 exhibit toxicity against the sensitive blood-stage Plasmodium falciparum 3D7 with IC50 in μM range. Conclusion: Thus, metal complex is a potentially viable candidate as antimalarial drug to overcome the emergence of drug resistance.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Mosquito larvicidal potential of tropical seaweeds: acetylcholinesterase inhibitory effects of bryopsis pennata, padina australis and sargassum binderi on Aedes aegypti (L.) and Aedes albopictus skuse

Ke-Xin Yu, Rohani Ahmad, Ching-Lee Wong, Ibrahim Jantan

Malaysian Journal of Medicine and Health Sciences, 2020;16(101):125-130.
MyJurnal

Introduction: Inhibition of the cholinesterase’s function leads to paralysis and death. This mechanism is served as a common mode of action of insecticide. The three tropical seaweeds, namely Bryopsis pennata, Padina australis and Sargassum binderi were reported for its potential mosquito larvicidal effect. In the present study, these seaweeds were evaluated for their potential as a cholinesterase inhibitor in the mechanism of larvicidal action. Methods: Ace- tylcholinsterase (AChE) inhibition assay was carried out based on the colorimetric method using a microplate reader. Phytochemical content of the seaweed extracts was screened by using liquid chromatography-mass spectroscopy (LC-MS). Results: Green seaweed B. pennata showed the strongest inhibition effect towards in vitro AChE by using
tissue homogenates of Aedes aegypti (IC50 value = 0.84 mg mL ) and Aedes albopictus as the enzyme source (IC
-1
value = 0.92 mg mL-1). The pattern of Lineweaver-Burk plots revealed that B. pennata was a mixed type inhibitor of
AChE, as the readings of Km, Vmax, Ki and Ki’, indicates that it had a strong inhibition ability with high binding affin- ity towards both free enzyme and enzyme-substrate complex. Conclusion: These findings suggest the compound(s) in
B. pennata extract serves as a promising source that could be developed into a mosquito larvicidal agent with AChE inhibition effect.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Curcumin from turmeric (Curcuma longa) induced apoptosis in human mammary carcinoma cells (MDA-MB-231)

Latifah, S. Y., Faujan, H. A., Sze, L. P., Raha, A. R., Hisyam, A. H., Li, O. C.

Malaysian Journal of Medicine and Health Sciences, 2006;2(2):71-79.
MyJurnal

Introduction: Curcumin, a natural compound present in turmeric (Curcuma longa) has been known to possess both anti-inflammatory and antioxidant effects. Objectives: The objectives of the study were to evaluate the cytotoxic activities and to determine the mode of cell death induced by curcumin towards the human mammary carcinoma cells (MDAMB-231). Methodology: Cytotoxicity of curcumin and its effect on cell viability were determined by using MTT assay and trypan blue dye exclusion method, respectively. The mode of cell death was detected by viewing under a light microscope and through DNA fragmentation analysis. Results and discussion: Curcumin was cytotoxic to MDA-MB-231 cells with the IC50 of 17.25 ì g/ml. Cell viability treatment using curcumin at concentrations of 30 ì g/ml and 10 ì g/ml was significantly (p

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Differential expression patterns of leukaemia associated genes in leukaemia cell lines compared to healthy controls

Ang Pei-Shen, Rajesh Ramasamy, Noor Hamidah Hussin, Cheong Soon-Keng, Seow Heng-Fong, Maha Abdullah

Malaysian Journal of Medicine and Health Sciences, 2016;12(1):0-0.
MyJurnal

Introduction: The phenotype and genotype of cancer cells portray hallmarks of cancer which may
have clinical value. Cancer cell lines are ideal models to study and confirm these characteristics. We
previously established two subtracted cDNA libraries with differentially expressed genes from an
acute myeloid leukaemia patient with poor prognosis (PP) and good prognosis (GP). Objective: To
compare gene expression of the leukaemia associated genes with selected biological characteristics
in leukaemia cell lines and normal controls. Methodology: Expression of 28 PP genes associated
with early fetal/embryonic development, HOX-related genes, hematopoiesis and aerobic glycolysis/
hypoxia genes and 36 GP genes involved in oxidative phosphorylation, protein synthesis, chromatin
remodelling and cell motility were examined in B-lymphoid (BV173, Reh and RS4;11) and myeloid
(HL-60, K562) leukaemia cell lines after 72h in culture as well as peripheral blood mononuclear cells
from healthy controls (N=5) using semi-quantitative polymerase chain reaction (PCR) method. Cell
cycle profiles were analysed on flow cytometry while MTT cytotoxicity assay was used to determine
drug resistance to epirubicin. Results: Genes expressed significantly higher in B-lymphoid leukaemia
cell lines compared to healthy controls were mostly of the GP library i.e. oxidative phosphorylation
(3/10), protein synthesis (4/11), chromatin remodelling (3/3) and actin cytoskeleton genes (1/5). Only
two genes with significant difference were from the PP library. Cancer associated genes, HSPA9 and
PSPH (GP library) and BCAP31 (PP library) were significantly higher in the B-lymphoid leukemia cell
lines. No significant difference was observed between myeloid cell lines and healthy controls. This
may also be due heterogeneity of cell lines studied. PBMC from healthy controls were not in cell cycle.
G2/M profiles and growth curves showed B-lymphoid cells just reaching plateau after 72 hour culture
while myeloid cells were declining. IC50 values from cytotoxicity assay revealed myeloid cell lines had
an average 13-fold higher drug resistance to epirubicin compared to B-lymphoid cell lines. Only CCL1,
was expressed at least two-fold higher in myeloid compared to B-lymphoid cell lines. In contrast,
MTRNR2, EEF1A1, PTMA, HLA-DR, C6orf115, PBX3, ENPP4, SELL, and IL3Ra were expressed
more than 2-fold higher in B-lymphoid compared to myeloid cell lines studied here. Conclusion: Thus,
B-lymphoid leukaemia cell lines here exhibited active, proliferating characteristics closer to GP genes.
Higher expression of several genes in B-lymphoid compared to myeloid leukaemia cell lines may be
useful markers to study biological differences including drug resistance between lineages.

Matched MeSH terms: Inhibitory Concentration 50
Polymer-albumin conjugate for the facilitated delivery of macromolecular platinum drugs

Dag A, Jiang Y, Karim KJ, Hart-Smith G, Scarano W, Stenzel MH

Macromol Rapid Commun, 2015 May;36(10):890-7.
PMID: 25790077 DOI: 10.1002/marc.201400576

The delivery of macromolecular platinum drugs into cancerous cells is enhanced by conjugating the polymer to albumin. The monomers N-(2-hydroxypropyl)methacrylamide (HPMA) and Boc protected 1,3-diaminopropan-2-yl acrylate (Ac-DAP-Boc) are copolymerized in the presence of a furan protected maleimide functionalized reversible addition-fragmentation chain transfer (RAFT) agent. The resulting polymer with a composition of P(HPMA14 -co-(Ac-DAP-Boc)9 ) and a molecular weight of Mn = 7600 g mol(-1) (Đ = 1.24) is used as a macromolecular ligand for the conjugation to the platinum drug. Thermogravimetric analysis reveals full conjugation. After deprotection of the maleimide functionality of the polymer, the reactive polymer is conjugated to albumin using the Cys34 functionality. The conjugation is monitored using size exclusion chromatography, MALDI-TOF (matrix assisted laser desorption ionization time-of-flight), and SDS Page (sodium dodecyl sulphate polyacrylamide gel electrophoresis). The polymer-albumin conjugates self-assemble in water into nanoparticles of sizes of around 80 nm thanks to the hydrophobic nature of the platinum drugs. The albumin coated nanoparticles are readily taken up by ovarian cancer cell lines and they show superior toxicity compared to a control sample without protein coating.

Matched MeSH terms: Inhibitory Concentration 50
Antiproliferative and apoptotic activities of 8-prenylnaringenin against human colon cancer cells

Koosha S, Mohamed Z, Sinniah A, Ibrahim Z, Seyedan A, Alshawsh MA

Life Sci, 2019 Jul 03.
PMID: 31278947 DOI: 10.1016/j.lfs.2019.116633

AIMS: The compound 8-prenylnaringenin (8-PN) is a prenylflavonoid that can be isolated from hops and beer and has anti-cancer properties against breast cancer. The aim of this study is to investigate the anti-proliferative and apoptotic activities of 8-PN against human colon cancer HCT-116 cells.
MAIN METHODS: Colon cancer HCT-116 cells were treated with 8-PN and subjected to MTT and acridine orange/propidium iodide (AO/PI) staining to investigate the cytotoxicity of 8-PN. Arrest of the cells at different phases of cell cycle was monitored in the presence of 8-PN. Moreover, the apoptotic effects of 8-PN was assessed via annexin V and caspase activity assays and compared to the untreated cells.
KEY FINDINGS: The findings showed that 8-PN revealed strong inhibitory effect against HCT-116 cells with an IC50 value of 23.83 ± 2.9 μg/ml after 48 h. However, at similar concentrations and experimental time-points, the compound did not show cytotoxic effect to non-cancerous colon cells (CCD-41). Annexin-V assay indicates that 38.5% and 14.4% of HCT-116 cells had entered early and late stages of apoptosis, respectively after exposure of the cells to 8-PN for 48 h. Caspase activity assay illustrates that apoptosis is activated through both intrinsic and extrinsic pathways. Moreover, flow cytometry cell cycle results indicate that treatment with 8-PN significantly arrested the HCT-116 cells at G0/G1 phase.
SIGNIFICANCE: These findings reveal that 8-PN has anti-proliferative activity against HCT-116 colon cancer cells via induction of intrinsic and extrinsic pathway-mediated apoptosis. Further investigations should be carried out to unravel the mechanistic pathways underlying these activities.

Matched MeSH terms: Inhibitory Concentration 50

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