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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 Aloe emodin enhances tamoxifen cytotoxicity effect on ER a-positive breast cancer cells, MCF-7, through downregulation of MEK1 and MEK2

Amin, I.M., Sheikh Abdul Kadir, S.H., Isa, M.R., Rosdy. N.M.M.N.M., Hasani NAH

JUMMEC, 2016;19(1):1-10.
MyJurnal

The positive response to tamoxifen in ERa-positive breast cancer patients is usually of a short duration as many
of the patients eventually develop resistance. Our preliminary results show that aloe emodin extracted from
the leaves of the Aloe barbadensis Miller demonstrated a cytotoxicity that is selective to ERa-positive breast
cancer cells (MCF-7), but not to ERa-negative breast cancer cells (MDA-MB-231) and to the control cells (MCF-
10A). The objective of this study was to test the hypothesis that aloe emodin may enhance the response of
MCF-7 cells to treatment with tamoxifen. MCF-7 cells were treated with aloe emodin alone, tamoxifen alone
or a combination of emodin and tamoxifen, at their respective IC50 concentrations and at different time points
of 24 hours, 48 hours and 72 hours. The respective IC50s were the concentrations of aloe emodin and tamoxifen
required to achieve 50% inhibition of the cells in the study. Cell viability and apoptosis were determined using
trypan blue exclusion and DNA fragmentation assays, respectively. The involvement of RAS/MEKs/ERKs genes
of MAPK signalling pathways with aloe emodin was determined using QuantiGene 2.0 Plex assay. Data was
evaluated using the one-way ANOVA test. Our findings showed that aloe emodin enhanced the cytotoxicity of
tamoxifen on MCF-7 cells through apoptosis by downregulation of MEK1/2 genes. Our research may provide a
rational basis for further in vivo studies to verify the efficacy of a combination of aloe emodin and tamoxifen
on the viability of ERa-positive-breast cancer cells.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cells

El Habbash AI, Mohd Hashim N, Ibrahim MY, Yahayu M, Omer FAE, Abd Rahman M, et al.

PeerJ, 2017;5:e3460.
PMID: 28740747 DOI: 10.7717/peerj.3460

Natural medicinal products possess diverse chemical structures and have been an essential source for drug discovery. Therefore, in this study, α-mangostin (AM) is a plant-derived compound was investigated for the apoptotic effect on human cervical cancer cells (HeLa). The cytotoxic effects of AM on the viability of HeLa and human normal ovarian cell line (SV40) were evaluated by using MTT assay. Results showed that AM inhibited HeLa cells viability at concentration- and time-dependent manner with IC50 value of 24.53 ± 1.48 µM at 24 h. The apoptogenic effects of AM on HeLa were assessed using fluorescence microscopy analysis. The effect of AM on cell proliferation was also studied through clonogenic assay. ROS production evaluation, flow cytometry (cell cycle) analysis, caspases 3/7, 8, and 9 assessment and multiple cytotoxicity assays were conducted to determine the mechanism of cell apoptosis. This was associated with G2/M phase cell cycle arrest and elevation in ROS production. AM induced mitochondrial apoptosis which was confirmed based on the significant increase in the levels of caspases 3/7 and 9 in a dose-dependent manner. Furthermore, the MMP disruption and increased cell permeability, concurrent with cytochrome c release from the mitochondria to the cytosol provided evidence that AM can induce apoptosis via mitochondrial-dependent pathway. AM exerted a remarkable antitumor effect and induced characteristic apoptogenic morphological changes on HeLa cells, which indicates the occurrence of cell death. This study reveals that AM could be a potential antitumor compound on cervical cancer in vitro and can be considered for further cervical cancer preclinical and in vivo testing.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Cholinesterase Inhibitory Activities of Adamantyl-Based Derivatives and Their Molecular Docking Studies

Kwong HC, Mah SH, Chia TS, Quah CK, Lim GK, Kumar CSC

Molecules, 2017 Jun 17;22(6).
PMID: 28629119 DOI: 10.3390/molecules22061005

Adamantyl-based compounds are clinically important for the treatments of type 2 diabetes and for their antiviral abilities, while many more are under development for other pharmaceutical uses. This study focused on the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of adamantyl-based ester derivatives with various substituents on the phenyl ring using Ellman's colorimetric method. Compound 2e with a 2,4-dichloro electron-withdrawing substituent on the phenyl ring exhibited the strongest inhibition effect against AChE, with an IC50 value of 77.15 µM. Overall, the adamantyl-based ester with the mono-substituent at position 3 of the phenyl ring exhibited good AChE inhibition effects with an ascending order for the substituents: Cl < NO₂ < CH₃ < OCH₃. Furthermore, compounds with electron-withdrawing groups (Cl and NO₂) substituted at position 3 on their phenyl rings demonstrated stronger AChE inhibition effects, in comparison to their respective positional isomers. On the other hand, compound 2j with a 3-methoxyphenyl ring showed the highest inhibition effect against BChE, with an IC50 value of 223.30 µM. Molecular docking analyses were conducted for potential AChE and BChE inhibitors, and the results demonstrated that the peripheral anionic sites of target proteins were predominant binding sites for these compounds through hydrogen bonds and halogen interactions instead of hydrophobic interactions in the catalytic active site.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Molecular attributes and apoptosis-inducing activities of a putative serine protease isolated from Tiger Milk mushroom (Lignosus rhinocerus) sclerotium against breast cancer cells in vitro

Yap HYY, Tan NH, Ng ST, Tan CS, Fung SY

PeerJ, 2018;6:e4940.
PMID: 29888137 DOI: 10.7717/peerj.4940

Background: The highly valued medicinal tiger milk mushroom (also known as Lignosus rhinocerus) has the ability to cure numerous ailments. Its anticancer activities are well explored, and recently a partially purified cytotoxic protein fraction termed F5 from the mushroom's sclerotial cold water extract consisting mainly of fungal serine proteases was found to exhibit potent selective cytotoxicity against a human breast adenocarcinoma cell line (MCF7) with IC50 value of 3.00 μg/ml. However, characterization of its cell death-inducing activity has yet to be established.
Methods: The mechanism involved in the cytotoxic activities of F5 against MCF7 cells was elucidated by flow cytometry-based apoptosis detection, caspases activity measurement, and expression profiling of apoptosis markers by western blotting. Molecular attributes of F5 were further mined from L. rhinocerus's published genome and transcriptome for future exploration.
Results and Discussion: Apoptosis induction in MCF7 cells by F5 may involve a cross-talk between the extrinsic and intrinsic apoptotic pathways with upregulation of caspase-8 and -9 activities and a marked decrease of Bcl-2. On the other hand, the levels of pro-apoptotic Bax, BID, and cleaved BID were increased accompanied by observable actin cleavage. At gene level, F5 composed of three predicted non-synonymous single nucleotide polymorphisms (T > C) and an alternative 5' splice site.
Conclusions: Findings from this study provide an advanced framework for further investigations on cancer therapeutics development from L. rhinocerus.

Matched MeSH terms: Inhibitory Concentration 50
DNA Nanostructures Carrying Stoichiometrically Definable Antibodies

Setyawati MI, Kutty RV, Leong DT

Small, 2016 Oct;12(40):5601-5611.
PMID: 27571230 DOI: 10.1002/smll.201601669

Targeted drug delivery is one of the key challenges in cancer nanomedicine. Stoichiometric and spatial control over the antibodies placement on the nanomedicine vehicle holds a pivotal role to overcome this key challenge. Here, a DNA tetrahedral is designed with available conjugation sites on its vertices, allowing to bind one, two, or three cetuximab antibodies per DNA nanostructure. This stoichiometrically definable cetuximab conjugated DNA nanostructure shows enhanced targeting on the breast cancer cells, which results with higher overall killing efficacy of the cancer cells.

Matched MeSH terms: Inhibitory Concentration 50
The Medicinal Uses, Toxicities and Anti-inflammatory Activity of Polyalthia Species (Annonaceae)

Yao LJ, Jalil J, Attiq A, Hui CC, Zakaria NA

J Ethnopharmacol, 2018 Oct 11.
PMID: 30316887 DOI: 10.1016/j.jep.2018.10.001

ETHNOPHARMACOLOGICAL RELEVANCE: Polyalthia is one of the largest and notable genera in Annonaceae family. Polyalthia species have been widely used in folklore medicine for the treatment of rheumatic fever, gastrointestinal ulcer and generalized body pain. Numerous in vitro and in vivo studies on Polyalthia Species have also corroborated the significant anti-inflammatory potential of its extracts and secondary metabolites.
AIM OF THE STUDY: This review is an attempt to assess the anti-inflammatory activity of Polyalthia species by giving critical appraisal and establishing evidences of their traditional uses. Moreover this review will highlight the lead compounds for future drug development that can serve as a potential anti-inflammatory drug with comparative efficacy and minimum side effects.
MATERIALS AND METHODS: An extensive literature review, focusing the anti-inflammatory potential of Polyalthia species was conducted using the following databases: PubMed, ScienceDirect, SpringerLink, Ovid, Scopus and ProQuest, as well as the locally available books, journals and relevant documents. The reference lists of retrieved papers were also searched for additional studies.
RESULTS: The Polyalthia species have shown significant anti-inflammatory activity through various mechanism of action. The most significant anti-inflammatory mechanism includes the inhibition of nuclear factor kappa B (NF-κB), prostaglandins (PGs), pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS). The data suggests that hydroxycleroda-3,13-dien-15,16-olide and 16-oxocleroda-3,13-dien-15-oic acid, quercetin, rutin, spinasterol, α-spinasterol, goniothalamin and (-)-5-hydroxygoniothalamin are the most potent anti-inflammatory compounds from Polyalthia species with comparable IC50 with positive controls.
CONCLUSIONS: Numerous pharmacological studies have supported the use of Polyalthia species against pain, rheumatic fever, haemorrhages and inflammation in traditional medicine. Flavonoids, diterpenoids, sterols and styrylpyrones from genus Polyalthia are the most significant class of compounds with potent anti-inflammatory activity. Secondary metabolites from these classes should be brought into further research to fill the gaps of knowledge in pharmacokinetics, pharmacodynamics, bioavailability, and toxicity in order to convert the pre-clinical results into clinical data for further investigation.

Matched MeSH terms: Inhibitory Concentration 50
Antidiabetic activities of chloroform fraction of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes

Anyanwu GO, Iqbal J, Khan SU, Zaib S, Rauf K, Onyeneke CE, et al.

J Ethnopharmacol, 2018 Oct 18.
PMID: 30342966 DOI: 10.1016/j.jep.2018.10.021

ETHNOPHARMACOLOGICAL RELEVANCE: Anthocleista vogelii Planch is a medicinal plant traditionally used in West Africa for the management and treatment of diabetes mellitus.
AIM OF THE STUDY: To determine the antidiabetic activities of chloroform fraction (CF) of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes.
MATERIALS AND METHODS: Inhibitory activities of CF against α-amylase and α-glucosidase activities were determined in vitro. Three weeks old rats were fed with high-fat diet for 9 weeks to induce obesity prior to further induction of diabetes using alloxan (150mg/kg body weight, i.p.). Blood glucose levels and body weight were measured every 7 days throughout the experiment. Glucose tolerance was assessed in normal and CF-treated rats on day 21. Terminal blood samples were collected from sacrificed animals for the measurement of serum insulin levels. Pancreases were excised from treated and untreated animals for histopathological examination.
RESULTS: LCMS/MS chromatographic profile of CF via positive and negative modes revealed 13 and 23 compounds respectively. Further analysis revealed quebrachitol (QCT), loganin, sweroside, oleoside 11-methyl ester and ferulic acid, which have been previously reported for their antidiabetic activities, as constituents of CF. CF inhibited activities of α-amylase (IC50 = 51.60 ± 0.92µg/ml) and α-glucosidase (IC50 = 5.86 ± 0.97µg/ml) in a dose-dependent manner. Treatment of animals with obesity-diabetes with 100 and 200mg/kg CF significantly improved glucose tolerance (P<0.001) and enhanced serum insulin levels (P<0.05) compared to diabetic control rats.
CONCLUSIONS: Antidiabetic activities of CF might be mediated via inhibition of α-amylase and α-glucosidase activities, elevation of serum insulin concentration, and enhancement of insulin and leptin sensitivity in obesity-diabetes rats. This study further substantiates the traditional use of A. vogelii in the management and treatment of diabetes in Africa and encourages further studies to investigate its mechanism of action.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells

Nassir AM, Shahzad N, Ibrahim IAA, Ahmad I, Md S, Ain MR

Saudi Pharm J, 2018 Sep;26(6):876-885.
PMID: 30202231 DOI: 10.1016/j.jsps.2018.03.009

Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC50 and IC90) of 15.6 ± 1.49 and 41.1 ± 2.19 μM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200 μM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext A rapid inhibitive enzyme assay for monitoring heavy metals pollution in the Juru Industrial Estate

Halmi, M.I.E., Baskaran Gunasekaran, Othman, A.R., Shukor, M.Y., Kamaruddin, K., Dahalan, F.A., et al.

Bioremediation Science and Technology Research, 2015;3(2):7-12.
MyJurnal

The volume of contaminated rivers in Malaysia continues to keep rising through the years. The
cost of instrumental monitoring is uneconomical and prohibits schedule monitoring of
contaminants particularly heavy metals. In this work, a rapid enzyme assay utilizing the
molybdenum-reducing enzyme as an inhibitive assay, prepared in crude form from the
molybdenum-reducing bacterium Serratia sp. strain DRY5 has been developed for monitoring
the heavy metals mercury, silver, copper and chromium in contaminated waters in the Juru
Industrial Estate. The crude enzyme extract transformed soluble molybdenum
(phosphomolybdate) into a deep blue solution, which is inhibited by heavy metals such as
mercury, silver, copper and chromium. The IC50 and Limits of Detection (LOD) values for
mercury, copper, silver and cadmium were 0.245, 0.298, 0.367, 0.326, and 0.124, 0.086, 0.088
and 0.094 mg L-1, respectively. The assay is rapid, and can be carried out in less than 10 minutes.
In addition, the assay can be carried out at ambient temperature. The IC50 values for these heavy
metals are more sensitive than several established assays. Water samples from various locations
in the month of November from the Juru Industrial Estate (Penang) were tested for the presence
of heavy metals using the developed assay. Enzyme activity was nearly inhibited for water
samples from several locations. The presence of heavy metals was confirmed instrumentally
using Atomic Emission Spectrometry and a Flow Injection Mercury System. The assay is rapid
and simple and can be used as a first screening method for large scale monitoring of heavy
metals.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Design, synthesis and biological evaluation of 3-(2-aminooxazol-5-yl)-2H-chromen-2-one derivatives

Kakkar S, Kumar S, Lim SM, Ramasamy K, Mani V, Shah SAA, et al.

Chem Cent J, 2018 Dec 04;12(1):130.
PMID: 30515643 DOI: 10.1186/s13065-018-0499-x

BACKGROUND: In view of wide range of biological activities of oxazole, a new series of oxazole analogues was synthesized and its chemical structures were confirmed by spectral data (Proton/Carbon-NMR, IR, MS etc.). The synthesized oxazole derivatives were screened for their antimicrobial and antiproliferative activities.
RESULTS AND DISCUSSION: The antimicrobial activity was performed against selected fungal and bacterial strains using tube dilution method. The antiproliferative potential was evaluated against human colorectal carcinoma (HCT116) and oestrogen- positive human breast carcinoma (MCF7) cancer cell lines using Sulforhodamine B assay and, results were compared to standard drugs, 5-fluorouracil and tamoxifen, respectively.
CONCLUSION: The performed antimicrobial activity indicated that compounds 3, 5, 6, 8 and 14 showed promising activity against selected microbial species. Antiproliferative screening found compound 14 to be the most potent compound against HCT116 (IC50 = 71.8 µM), whereas Compound 6 was the most potent against MCF7 (IC50 = 74.1 µM). Further, the molecular docking study has been carried to find out the interaction between active oxazole compounds with CDK8 (HCT116) and ER-α (MCF7) proteins indicated that compound 14 and 6 showed good dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Changes in the Carbon Metabolism of Escherichia coli During the Evolution of Doxycycline Resistance

Yang Y, Mi J, Liang J, Liao X, Ma B, Zou Y, et al.

Front Microbiol, 2019;10:2506.
PMID: 31736928 DOI: 10.3389/fmicb.2019.02506

Despite our continuous improvement in understanding the evolution of antibiotic resistance, the changes in the carbon metabolism during the evolution of antibiotic resistance remains unclear. To investigate the evolution of antibiotic resistance and the changes in carbon metabolism under antibiotic pressure, Escherichia coli K-12 was evolved for 38 passages under a concentration gradient of doxycycline (DOX). The 0th-passage sensitive strain W0, the 20th-passage moderately resistant strain M20, and the 38th-passage highly resistant strain E38 were selected for the determination of biofilm formation, colony area, and carbon metabolism levels, as well as genome and transcriptome sequencing. The MIC of DOX with E. coli significantly increased from 4 to 96 μg/ml, and the IC50 increased from 2.18 ± 0.08 to 64.79 ± 0.75 μg/ml after 38 passages of domestication. Compared with the sensitive strain W0, the biofilm formation amount of the resistant strains M20 and E38 was significantly increased (p < 0.05). Single-nucleotide polymorphisms (SNPs) were distributed in antibiotic resistance-related genes such as ribosome targets, cell membranes, and multiple efflux pumps. In addition, there were no mutated genes related to carbon metabolism. However, the genes involved in the biosynthesis of secondary metabolites and carbon metabolism pathway were downregulated, showing a significant decrease in the metabolic intensity of 23 carbon sources (p < 0.05). The results presented here show that there may be a correlation between the evolution of E. coli DOX resistance and the decrease of carbon metabolism, and the mechanism was worthy of further research, providing a theoretical basis for the prevention and control of microbial resistance.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Cytotoxicity, regulation of apoptotic and anti-apoptotic gene expression by IL-27 in MCF-7 and MDA-MB-231 breast cancer cell lines

Yap Wei Boon, Shaktypreya Nadarajah, Nadiah Shidik, Noorjahan Banu Mohammed Alitheen

Jurnal Sains Kesihatan Malaysia, 2018;16(101):15-22.
MyJurnal

Breast cancer is one of the commonest cancers among women. Conventional therapies cause adverse side effects in patients. Cytokine immunotherapy such as interleukin-27 (IL-27) has been sought as an alternative cancer treatment in recent years. IL-27 has been shown to improve anticancer immunity and anti-angiogenesis in cancers, however, its effect on apoptotic and anti-apoptotic gene expression especially in breast cancers is yet to be explored. Cytotoxicity of IL-27 in non-cancerous (184b5) and cancerous (MCF-7 and MDA-MB-231) breast cell lines was first determined for 24-72 h in this study. The results indicated that IL-27 treatment did not retard 184b5 cell growth, however, did inhibit MCF-7 (48 h) and MDA-MB-231 (72 h) cell growth with IC50 at 442 and 457 ng/ml, respectively. Apoptotic (TRAIL, FADD, FAS, caspase-3 and caspase-8) and anti-apoptotic (BCL-2, AKT, and COX-2) genes were then amplified from untreated (control) and treated breast cancer cells and studied. TRAIL, caspase-3, caspase-8 gene expression was significantly (p < 0.05) upregulated in treated MCF-7 (442 ng/ml) and MDA-MB-231 (457 ng/ml) cells. Expression of FADD and FAS genes was not detected in both control and treated MCF-7 and MDA-MB-231 cells. COX-2 gene was also not expressed by MCF-7 cells, but reduced significantly (p < 0.05) in treated MDA-MB-231 cells. In MDA-MB-231 cells, IL-27 treatment seemed to slightly enhance the expression of AKT and BCL-2 genes which, on the other hand, was downregulated in treated MCF-7 cells. Conclusively, IL-27 is able to inhibit breast cancer cell growth and regulate apoptotic and anti-apoptotic gene expression in breast cancer cells.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Cytotoxicity effect of quercus infectoria based vaginal cream on hela cells and its preliminary in vivo toxicity evaluation towards female rats

Hazwani M.Y., Hasmah A., Wan Amir Nizam W.A.

International Medical Journal Malaysia, 2018;17(2):99-106.
MyJurnal

Introduction: Cervical cancer is the third leading cause of cancer death among females in less developed countries. Drugs used in the treatment of cervical cancer were reported to exert a cytotoxic effect on the normal cells. This study aimed to determine the effectiveness of Quercus infectoria (QI) vaginal cream towards cervical cancer cell, HeLa and its toxicity effect on the female rat model. Methods: MTT assays were utilized to determine the median concentration (IC50) for cell cytotoxicity of QIA and QI vaginal cream against cervical cancer cells, HeLa. Expression of HPV E6 and E7 protein in HeLa cells treated with QI vaginal cream for 24 hours were conducted by Western blot analysis. In separate experiments, the toxicity of QI vaginal cream on a lower reproductive tract of the female rat model has been assessed by histopathological examination after application for three weeks. The antioxidant activity of QIA extract and QI vaginal cream were assessed by DPPH radical scavenging assay. Results: A moderate cytotoxicity activity exerted by QIA extract and QI vaginal cream against HeLa cell with IC50 values of 13.90 ± 2.27, and 20.80 ± 1.94 respectively. Furthermore, QI vaginal cream suppressed the expression of HPV E6 and E7. Daily application of QI vaginal did not exert any inflammation to the vaginal mucosa and cervix. QIA extract and QI vaginal cream demonstrated high DPPH radical scavenging activity. Conclusion: Formulated QI vaginal cream has cytotoxic effect on HeLa cells without causing an adverse effect on the lower reproductive tract in female rat model.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Isoniazid Conjugated Magnetic Nanoparticles Loaded with Amphotericin B as a Potent Antiamoebic Agent against Acanthamoeba castellanii

Iqbal K, Abdalla SAO, Anwar A, Iqbal KM, Shah MR, Anwar A, et al.

Antibiotics (Basel), 2020 May 25;9(5).
PMID: 32466210 DOI: 10.3390/antibiotics9050276

The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, granulomatous amoebic encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these infections; however, the host cell cytotoxicity of these drugs remains a challenge. Furthermore, Acanthamoeba species are capable of transforming to the cyst form to resist chemotherapy. Herein, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with isoniazid, which were further loaded with amphotericin B (ISO-NPs-AMP) to cause potent antiamoebic effects against Acanthamoeba castellanii. The IC50 of isoniazid conjugated with magnetic nanoparticles and loaded with amphotericin B was found to be 45 μg/mL against Acanthamoeba castellanii trophozoites and 50 μg/mL against cysts. The results obtained in this study have promising implications in drug discovery as these nanomaterials exhibited high trophicidal and cysticidal effects, as well as limited cytotoxicity against rat and human cells.

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 Antiproliferative and Apoptotic Effects of Cardamonin against Hepatocellular Carcinoma HepG2 Cells

Badroon NA, Abdul Majid N, Alshawsh MA

Nutrients, 2020 Jun 12;12(6).
PMID: 32545423 DOI: 10.3390/nu12061757

Liver cancer is the sixth most common cancer in terms of incidence and the fourth in terms of mortality. Hepatocellular carcinoma (HCC) represents almost 90% of primary liver cancer and has become a major health problem globally. Cardamonin (CADMN) is a natural bioactive chalcone found in several edible plants such as cardamom and Alpinia species. Previous studies have shown that CADMN possesses anticancer activities against breast, lung, prostate and colorectal cancer. In the present study, the mechanisms underlying the anti-hepatocellular carcinoma effects of CADMN were investigated against HepG2 cells. The results demonstrated that CADMN has anti-proliferative effects and apoptotic action on HepG2 cells. CADMN showed potent cytotoxicity against HepG2 cells with an IC50 of 17.1 ± 0.592 μM at 72 h. Flow cytometry analysis demonstrated that CADMN arrests HepG2 cells in G1 phase and induces a significant increase in early and late apoptosis in a time-dependent manner. The mechanism by which CADMN induces apoptotic action was via activation of both extrinsic and intrinsic pathways. Moreover, the findings of this study showed the involvement of reactive oxygen species (ROS), which inhibit the NF-κB pathway and further enhance the apoptotic process. Together, our findings further support the potential anticancer activity of CADMN as an alternative therapeutic agent against HCC.

Matched MeSH terms: Inhibitory Concentration 50
3,4-Dimethoxybenzohydrazide derivatives as antiulcer: Molecular modeling and density functional studies

Taha M, Ismail NH, Zaki HM, Wadood A, Anouar EH, Imran S, et al.

Bioorg Chem, 2017 12;75:235-241.
PMID: 29031169 DOI: 10.1016/j.bioorg.2017.10.004

3,4-Dimethoxybenzohydrazide derivatives (1-25) have been synthesized and evaluated for their urease inhibitory potential. Among the series, compounds 2, 3, 4 and 5 with IC50 values 12.61 ± 0.07, 18.24 ± 0.14, 19.22 ± 0.21, and 8.40 ± 0.05 µM, respectively, showed excellent urease inhibitory potentials when compared with standard thiourea (IC50 value 21.40 ± 0.21 µM). Compounds 1, 6, 8, 18, 19 and 20 also showed good to moderate inhibition, while the remaining compounds were found to be completely inactive. The structures of compounds 6 and 25 were confirmed through X-ray crystallography while the structures of remaining compounds were confirmed through ESI-MS and 1H NMR. Molecular docking studies were performed understand the binding interactions with enzyme active site. The synthesized compounds were evaluated for cytotoxicity and found to be nontoxic.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Eco-Friendly Formulated Zinc Oxide Nanoparticles: Induction of Cell Cycle Arrest and Apoptosis in the MCF-7 Cancer Cell Line

Boroumand Moghaddam A, Moniri M, Azizi S, Abdul Rahim R, Bin Ariff A, Navaderi M, et al.

Genes (Basel), 2017 Oct 20;8(10).
PMID: 29053567 DOI: 10.3390/genes8100281

Green products have strong potential in the discovery and development of unique drugs. Zinc oxide nanoparticles (ZnO NPs) have been observed to have powerful cytotoxicity against cells that cause breast cancer. The present study aims to examine the cell cycle profile, status of cell death, and pathways of apoptosis in breast cancer cells (MCF-7) treated with biosynthesized ZnO NPs. The anti-proliferative activity of ZnO NPs was determined using MTT assay. Cell cycle analysis and the mode of cell death were evaluated using a flow cytometry instrument. Quantitative real-time-PCR (qRT-PCR) was employed to investigate the expression of apoptosis in MCF-7 cells. ZnO NPs were cytotoxic to the MCF-7 cells in a dose-dependent manner. The 50% growth inhibition concentration (IC50) of ZnO NPs at 24 h was 121 µg/mL. Cell cycle analysis revealed that ZnO NPs induced sub-G₁ phase (apoptosis), with values of 1.87% at 0 μg/mL (control), 71.49% at IC25, 98.91% at IC50, and 99.44% at IC75. Annexin V/propidium iodide (PI) flow cytometry analysis confirmed that ZnO NPs induce apoptosis in MCF-7 cells. The pro-apoptotic genes p53, p21, Bax, and JNK were upregulated, whereas anti-apoptotic genes Bcl-2, AKT1, and ERK1/2 were downregulated in a dose-dependent manner. The arrest and apoptosis of MCF-7 cells were induced by ZnO NPs through several signalling pathways.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Increased Loading, Efficacy and Sustained Release of Silibinin, a Poorly Soluble Drug Using Hydrophobically-Modified Chitosan Nanoparticles for Enhanced Delivery of Anticancer Drug Delivery Systems

Kuen CY, Fakurazi S, Othman SS, Masarudin MJ

Nanomaterials (Basel), 2017 Nov 08;7(11).
PMID: 29117121 DOI: 10.3390/nano7110379

Conventional delivery of anticancer drugs is less effective due to pharmacological drawbacks such as lack of aqueous solubility and poor cellular accumulation. This study reports the increased drug loading, therapeutic delivery, and cellular accumulation of silibinin (SLB), a poorly water-soluble phenolic compound using a hydrophobically-modified chitosan nanoparticle (pCNP) system. In this study, chitosan nanoparticles were hydrophobically-modified to confer a palmitoyl group as confirmed by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) assay. Physicochemical features of the nanoparticles were studied using the TNBS assay, and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analyses. The FTIR profile and electron microscopy correlated the successful formation of pCNP and pCNP-SLB as nano-sized particles, while Dynamic Light Scattering (DLS) and Field Emission-Scanning Electron Microscopy (FESEM) results exhibited an expansion in size between pCNP and pCNP-SLB to accommodate the drug within its particle core. To evaluate the cytotoxicity of the nanoparticles, a Methylthiazolyldiphenyl-tetrazolium bromide (MTT) cytotoxicity assay was subsequently performed using the A549 lung cancer cell line. Cytotoxicity assays exhibited an enhanced efficacy of SLB when delivered by CNP and pCNP. Interestingly, controlled release delivery of SLB was achieved using the pCNP-SLB system, conferring higher cytotoxic effects and lower IC50 values in 72-h treatments compared to CNP-SLB, which was attributed to the hydrophobic modification of the CNP system.

Matched MeSH terms: Inhibitory Concentration 50

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