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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 A Quantum Chemical and Statistical Study of Cytotoxic Activity of Compounds Isolated from Curcuma zedoaria

Hamdi OA, Anouar el H, Shilpi JA, Trabolsy ZB, Zain SB, Zakaria NS, et al.

Int J Mol Sci, 2015 Apr 27;16(5):9450-68.
PMID: 25923077 DOI: 10.3390/ijms16059450

A series of 21 compounds isolated from Curcuma zedoaria was subjected to cytotoxicity test against MCF7; Ca Ski; PC3 and HT-29 cancer cell lines; and a normal HUVEC cell line. To rationalize the structure-activity relationships of the isolated compounds; a set of electronic; steric and hydrophobic descriptors were calculated using density functional theory (DFT) method. Statistical analyses were carried out using simple and multiple linear regressions (SLR; MLR); principal component analysis (PCA); and hierarchical cluster analysis (HCA). SLR analyses showed that the cytotoxicity of the isolated compounds against a given cell line depend on certain descriptors; and the corresponding correlation coefficients (R2) vary from 0%-55%. MLR results revealed that the best models can be achieved with a limited number of specific descriptors applicable for compounds having a similar basic skeleton. Based on PCA; HCA and MLR analyses; active compounds were classified into subgroups; which was in agreement with the cell based cytotoxicity assay.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Total phenolics contents and free radical scavenging capacity of piper sarmentosum (pucuk kaduk) extract

Hanapi Mat Jusoh, Normah Haron, Sarah Haryati Binti Mohd Zohari

International Journal of Allied Health Sciences, 2019;3(4):876-883.
MyJurnal

Introduction: Piper sarmentosum is one of the herbaceous plants that has been used as natural antioxidant to source to treat diseases. This study was conducted to determine the total phenolic contents (TPC) and free radical scavenging capacity in free and bound (soluble and insoluble) of P. sarmentosum. Methods: Free phenolic extract was acquired through direct methanol extraction while acidic and alkaline hydrolyses were adopted to release the bound phenolic acids. The TPC was determined by using Folin-Ciocalteu assay and is expressed as Gallic Acid equivalent (GAE) in miligrams per gram of extracts. The antioxidant scavenging capacity was determined by using DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay. Results: Insoluble bound phenolic extract of P. sarmentosum showed the highest TPC value (1.54 ± 0.04 mg GAE/g DW) followed by soluble phenolic extract and free extract (1.13 ± 0.10 and 0.57 ± 0.06 mg GAE/g DW, respectively). The soluble phenolic fraction has expressed the highest free radical scavenging capacity (76.57± 4.12%) followed by insoluble (69.79± 2.33 %) and free extracts (58.15± 4.44 %). The IC50 values for free, soluble and insoluble bound phenolic were 24.05 ± 3.81, 16.17 ± 1.84 and 18.49 ± 1.92 mg/ml, respectively. Conclusions: The significant differences between all the extracts and antioxidant inhibition in this present study suggested that different forms (free and bound) of extracts did influence the radical scavenging capacity as a whole.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Total phenolic content and the antioxidant activity of clinacanthus nutans extract

Hanapi Mat Jusoh, Normah Haron, Nurul Syamimi Zailani

International Journal of Allied Health Sciences, 2019;3(4):904-913.
MyJurnal

Introduction: Clinacanthus nutans is used as natural nutraceuticals for prevention and treatment of cancer. The purpose of this study is to (i) determine the total phenolic content and antioxidant scavenging capacities of C. nutans in free and bound phenolic acid and (ii) study the relationship between TPC and antioxidant scavenging capacities of C. nutans. Methods: The total phenolic contents were measured using Folin-Ciocalteu assay. Free and bound phenolic were examined by using spectrophotometer while antioxidant capacity were evaluated using DPPH (2, 2-diphenyl-1-picrylhydrazyl) scavenging activity assay. Results: Insoluble phenolic acids showed the highest amount of total phenolic content in C. nutans extracts (6.09+ 0.45 mg gallic acid equivalent (GAE)/ g DW) and exhibited highest antioxidant activity (73.3+0.82 %) as compared to free and soluble phenolic extracts. The IC50 values for free phenolic, soluble bound and insoluble bound phenolic extracts were 0.69+0.02 mg/mL, 0.64+0.04 and 0.60+0.006 mg/mL, respectively. There were positive correlation between insoluble bound phenolic content of C. nutans extracts with antioxidant radical scavenging capacity (R2 = 0.893). Conclusions: These results indicate that different phenolic acid forms affect the total phenolic content and antioxidant properties. Natural compounds such as phenolics from C. nutans could be a good source of antioxidant.

Matched MeSH terms: Inhibitory Concentration 50
In vitro inhibitory mechanisms and molecular docking of 1'-S-1'-acetoxychavicol acetate on human cytochrome P450 enzymes

Haque AKMM, Leong KH, Lo YL, Awang K, Nagoor NH

Phytomedicine, 2017 Jul 15;31:1-9.
PMID: 28606510 DOI: 10.1016/j.phymed.2017.05.002

BACKGROUND: The compound, 1'-S-1'-acetoxychavicol acetate (ACA), isolated from the rhizomes of a Malaysian ethno-medicinal plant, Alpinia conchigera Griff. (Zingiberaceae), was previously shown to have potential in vivo antitumour activities. In the development of a new drug entity, potential interactions of the compound with the cytochrome P450 superfamily metabolizing enzymes need to be ascertain.
PURPOSE: The concomitant use of therapeutic drugs may cause potential drug-drug interactions by decreasing or increasing plasma levels of the administered drugs, leading to a suboptimal clinical efficacy or a higher risk of toxicity. Thus, evaluating the inhibitory potential of a new chemical entity, and to clarify the mechanism of inhibition and kinetics in the various CYP enzymes is an important step to predict drug-drug interactions.
STUDY DESIGN: This study was designed to assess the potential inhibitory effects of Alpinia conchigera Griff. rhizomes extract and its active constituent, ACA, on nine c-DNA expressed human cytochrome P450s (CYPs) enzymes using fluorescent CYP inhibition assay.
METHODS/RESULTS: The half maximal inhibitory concentration (IC50) of Alpinia conchigera Griff. rhizomes extract and ACA was determined for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5. A. conchigera extract only moderately inhibits on CYP3A4 (IC50 = 6.76 ± 1.88µg/ml) whereas ACA moderately inhibits the activities of CYP1A2 (IC50 = 4.50 ± 0.10µM), CYP2D6 (IC50 = 7.50 ± 0.17µM) and CYP3A4 (IC50 = 9.50 ± 0.57µM) while other isoenzymes are weakly inhibited. In addition, mechanism-based inhibition studies reveal that CYP1A2 and CYP3A4 exhibited non-mechanism based inhibition whereas CYP2D6 showed mechanism-based inhibition. Lineweaver-Burk plots depict that ACA competitively inhibited both CYP1A2 and CYP3A4, with a Ki values of 2.36 ± 0.03 µM and 5.55 ± 0.06µM, respectively, and mixed inhibition towards CYP2D6 with a Ki value of 4.50 ± 0.08µM. Further, molecular docking studies show that ACA is bound to a few key amino acid residues in the active sites of CYP1A2 and CYP3A4, while one amino residue of CYP2D6 through predominantly Pi-Pi interactions.
CONCLUSION: Overall, ACA may demonstrate drug-drug interactions when co-administered with other therapeutic drugs that are metabolized by CYP1A2, CYP2D6 or CYP3A4 enzymes. Further in vivo studies, however, are needed to evaluate the clinical significance of these interactions.

Matched MeSH terms: Inhibitory Concentration 50
Effects of tocotrienols on cell viability and apoptosis in normal murine liver cells (BNL CL.2) and liver cancer cells (BNL 1ME A.7R.1), in vitro

Har CH, Keong CK

Asia Pac J Clin Nutr, 2005;14(4):374-80.
PMID: 16326644

The effects of tocotrienols on murine liver cell viability and their apoptotic events were studied over a dose range of 0-32 microg mL(-1). Normal murine liver cells (BNL CL.2) and murine liver cancer cells (BNL 1ME A.7R.1) were treated with tocotrienols (T(3)), alpha tocopherol (alpha-T) and the chemo drug, Doxorubicin (Doxo, as a positive control). Cell viability assay showed that T(3) significantly (P < or = 0.05) lowered the percentage of BNL 1ME A.7R.1 cell viability in a dose-responsive manner (8-16 microg mL(-1)), whereas T did not show any significant (P>0.05) inhibition in cell viability with increasing treatment doses of 0-16 microg mL(-1). The IC(50) for tocotrienols were 9.8, 8.9, 8.1, 9.7, 8.1 and 9.3 microg mL(-1) at 12, 24, 36, 48, 60 and 72 hours respectively. Early apoptosis was detected 6 hours following T(3) treatment of BNL 1ME A.7R.1 liver cancer cells, using Annexin V-FITC fluorescence microscopy assay for apoptosis, but none were observed for the non-treated liver cancer cells at the average IC(50) of 8.98 microg mL(-1) tocotrienols for liver cancer cells. Several apoptotic bodies were detected in BNL 1ME A.7R.1 liver cancer cells at 6 hours post-treatment with tocotrienols (8.98 microg mL(-1)) using Acridine Orange/Propidium Iodide fluorescence assay. However, only a couple of apoptotic bodies were seen in the non-treated liver cancer cells and the BNL CL.2 normal liver cells. Some mitotic bodies were also observed in the T(3)-treated BNL 1ME A.7R.1 liver cancer cells but were not seen in the untreated BNL 1ME A.7R.1 cells and the BNL CL.2 liver cells. Following T(3)-treatment (8.98 microg mL(-1)) of the BNL 1ME A.7R.1 liver cancer cells, 24.62%, 25.53% and 44.90% of the cells showed elevated active caspase 3 activity at 9, 12 and 24 hours treatment period, respectively. DNA laddering studies indicated DNA fragmentation occurred in the T(3)-treated liver cancer cells, BNL 1ME A.7R.1 but not in non-treated liver cancer cells and the T(3)-treated and non-treated normal liver cells. These results suggest that tocotrienols were able to reduce the cell viability in the murine liver cancer cells at a dose of 8-32 microg mL(-1) and that this decrease in percentage cell viability may be due to apoptosis.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay

Hariono M, Abdullah N, Damodaran KV, Kamarulzaman EE, Mohamed N, Hassan SS, et al.

Sci Rep, 2016 12 20;6:38692.
PMID: 27995961 DOI: 10.1038/srep38692

We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Cytotoxic Effect of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) on Liver Cancer Cell Integrated with Hepatitis B Genome, Hep3B

Haron AS, Syed Alwi SS, Saiful Yazan L, Abd Razak R, Ong YS, Zakarial Ansar FH, et al.

Evid Based Complement Alternat Med, 2018;2018:1549805.
PMID: 30186351 DOI: 10.1155/2018/1549805

Thymoquinone (TQ), a bioactive compound found in Nigella sativa, cannot be orally consumed due to its lipophilicity. In order to overcome this low bioavailability, TQ is loaded into a colloidal drug carrier known as a nanostructured lipid carrier (NLC). This study aims to determine the antiproliferative effects of TQ and TQ-NLC on liver cancer cells integrated with the hepatitis B genome, Hep3B. The Hep3B was treated with TQ or TQ-NLC for 24, 48, and 72 hours via MTT assay. The results confirm that TQ or TQ-NLC inhibited the growth of Hep3B at IC50 <16.7 μM for 72 hours. TQ was also found to induce cell cycle arrest at the G1 checkpoint while TQ-NLC induced non-phase-specific cell cycle arrest. Further analysis using Annexin V staining confirmed the apoptotic induction of TQ or TQ-NLC via activation of caspases-3/7. In ROS management, TQ acted as a prooxidant (increased the level of ROS), while TQ-NLC acted as an antioxidant (reduced the level of ROS). Molecular analysis demonstrated that the GSH system and the Nrf2/Keap1 signaling pathway in Hep3B influenced the differential responses of the cells towards TQ or TQ-NLC. Hence, this study demonstrated that TQ and TQ-NLC have in vitro anticancer effects on the Hep3B.

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 Synthesis and Optimization of Mesoporous Silica Nanoparticles for Ruthenium Polypyridyl Drug Delivery

Harun SN, Ahmad H, Lim HN, Chia SL, Gill MR

Pharmaceutics, 2021 Jan 24;13(2).
PMID: 33498795 DOI: 10.3390/pharmaceutics13020150

The ruthenium polypyridyl complex [Ru(dppz)2PIP]2+ (dppz: dipyridophenazine, PIP: (2-(phenyl)-imidazo[4,5-f ][1,10]phenanthroline), or Ru-PIP, is a potential anticancer drug that acts by inhibiting DNA replication. Due to the poor dissolution of Ru-PIP in aqueous media, a drug delivery agent would be a useful approach to overcome its limited bioavailability. Mesoporous silica nanoparticles (MSNs) were synthesized via a co-condensation method by using a phenanthrolinium salt with a 16 carbon length chain (Phen-C16) as the template. Optimization of the synthesis conditions by Box-Behnken design (BBD) generated MSNs with high surface area response at 833.9 m2g-1. Ru-PIP was effectively entrapped in MSNs at 18.84%. Drug release profile analysis showed that Ru-PIP is gradually released, with a cumulative release percentage of approximately 50% at 72 h. The release kinetic profile implied that Ru-PIP was released from MSN by diffusion. The in vitro cytotoxicity of Ru-PIP, both free and MSN-encapsulated, was studied in Hela, A549, and T24 cancer cell lines. While treatment of Ru-PIP alone is moderately cytotoxic, encapsulated Ru-PIP exerted significant cytotoxicity upon all the cell lines, with half maximal inhibitory concentration (IC50) values determined by MTT (([3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide]) assay at 48 h exposure substantially decreasing from >30 µM to <10 µM as a result of MSN encapsulation. The mechanistic potential of cytotoxicity on cell cycle distribution showed an increase in G1/S phase populations in all three cell lines. The findings indicate that MSN is an ideal drug delivery agent, as it is able to sustainably release Ru-PIP by diffusion in a prolonged treatment period.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext The role of miRNAs 34a, 146a, 320a and 542 in the synergistic anticancer effects of methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC) with doxorubicin in breast cancer cells

Hasanpourghadi M, Abdul Majid N, Rais Mustafa M

PeerJ, 2018;6:e5577.
PMID: 30245930 DOI: 10.7717/peerj.5577

Combination Index (CI) analysis suggested that MBIC and doxorubicin synergistically inhibited up to 97% of cell proliferation in ER+/PR+MCF-7 and triple negative MDA-MB-231 breast cancer cell lines. Moreover, treatment of the breast cancer cells with the combined drugs resulted in lower IC50 values in contrast to the individual drug treatment. Small noncoding microRNAs (miRNA) may function as non-mutational gene regulators at post-transcriptional level of protein synthesis. In the present study, the effect of the combined treatment of MBIC and doxorubicin on the expression level of several miRNAs including miR-34a, miR-146a, miR-320a and miR-542 were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. These miRNAs have the potential to alter the protein level of survivin, the anti-apoptotic protein and reduce the metastatic activity in human breast cancer cell lines by interfering with the nuclear accumulation of NF-κB. Our results demonstrated the several fold changes in expression of miRNAs, which is drug and cell line dependent. This finding demonstrated a functional synergistic network between miR-34a, miR-320a and miR-542 that are negatively involved in post-transcriptional regulation of survivin in MCF-7 cells. While in MDA-MB-231 cells, changes in expression level of miR-146a was correlated with inhibition of the nuclear translocation of NF-κB. The overall result suggested that alteration in protein level and location of survivin and NF-κB by miR-34a, miR-320a, miR-146a and miR-542, remarkably influenced the synergistic enhancement of combined MBIC and doxorubicin in treatment of aggressive and less aggressive human breast cancer cell lines.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Antioxidant, antimicrobial and tyrosinase inhibitory activities of xanthones isolated from Artocarpus obtusus F.M. Jarrett

Hashim NM, Rahmani M, Ee GC, Sukari MA, Yahayu M, Amin MA, et al.

Molecules, 2012;17(5):6071-82.
PMID: 22614861 DOI: 10.3390/molecules17056071

One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical scavenger towards DPPH free radicals with IC50 value of 2 µg/mL with prominent discoloration observed in comparison with standard ascorbic acid, α-tocopherol and quercetin, The compound also exhibited antibacterial activity against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus subtilis (clinically isolated) with inhibition zone of 20 and 12 mm, respectively. However the other two xanthones were found to be inactive. For the tyrosinase inhibitory activity, again compound (1) displayed strong activity comparable with the standard kojic acid.

Matched MeSH terms: Inhibitory Concentration 50
1'S-1'-acetoxyeugenol acetate: a new chemotherapeutic natural compound against MCF-7 human breast cancer cells

Hasima N, Aun LI, Azmi MN, Aziz AN, Thirthagiri E, Ibrahim H, et al.

Phytomedicine, 2010 Oct;17(12):935-9.
PMID: 20729047 DOI: 10.1016/j.phymed.2010.03.011

Medicinal plants containing active natural compounds have been used as an alternative treatment for cancer patients in many parts of the world especially in Asia (Itharat et al. 2004). In this report, we describe the cytotoxic and apoptotic properties of 1'S-1'-acetoxyeugenol acetate (AEA), an analogue of 1'S-1'-acetoxychavicol acetate (ACA), isolated from the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) on human breast cancer cells. Data from MTT cell viability assays indicated that AEA induced both time- and dose-dependent cytotoxicity with an IC(50) value of 14.0 μM within 36 h of treatment on MCF-7 cells, but not in HMEC normal control cells. Both annexin V-FITC/PI flow cytometric analysis and DNA fragmentation assays confirmed that AEA induced cell death via apoptosis. AEA was also found to induce cell cycle arrest in MCF-7 cells at the G(0)/G(1) phase with no adverse cell cycle arrest effects on HMEC normal control cells. It was concluded that AEA isolated from the Malaysian tropical ginger represents a potential chemotherapeutic agent against human breast cancer cells with higher cytotoxicity potency than its analogue, ACA.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext In vitro antiplasmodial activity, macronutrients and trace metals in the medicinal plants: Phyllanthus spp. and Alpinia conchigera Griff

Haslinda MS, Aiyub Z, Bakar NK, Tohar N, Musa Y, Abdullah NR, et al.

Trop Biomed, 2015 Mar;32(1):129-39.
PMID: 25801263

An antiplasmodial screening of Phyllanthus debilis and Phyllanthus urinaria was carried out. The medicinal plants were extracted and evaluated for in vitro antiplasmodial activity against D10 (chloroquine-sensitive, CQS) and Gombak A (chloroquine-resistant, CQR) strains of Plasmodium falciparum. The methanolic crudes from the soxhlet extraction were active against both strains however, P. urinaria (IC50 8.9 μg/ml with CQR strain) exhibited better anti-malarial activity compared to P. debilis (IC50 12.2 μg/ml with CQR strain). Furthermore, the methanolic crude of P. urinaria obtained by the cold extraction has good anti-malarial activity towards CQS (IC50 4.1 μg/ml). The concentration of macronutrients (calcium and magnesium) and trace metals (copper, manganese, iron and zinc) from three Phyllanthus species i.e. P. debilis Klein ex Wild., Phyllanthus niruri L., P. urinaria L. and Alpinia conchigera Griff. were determined using microwave digestion method and analyzed by Flame Atomic Absorption Spectroscopy. Standard Reference Material 1547 (peach leaves) was used to validate the method throughout this study. The recovery values were in the range of 80% to 120% which were in very good agreement with the certified values. The three Phyllanthus species and leaves of A. conchigera showed the highest concentration of calcium compared to other metals and macronutrients studied. The significant presence of all the important macronutrients and trace metals which are essential for human health and well-being substantiate their use medicinally in traditional practices.

Matched MeSH terms: Inhibitory Concentration 50
Apoptosis induced by desmethyl-lasiodiplodin is associated with upregulation of apoptotic genes and downregulation of monocyte chemotactic protein-3

Hazalin NA, Lim SM, Cole AL, Majeed AB, Ramasamy K

Anticancer Drugs, 2013 Sep;24(8):852-61.
PMID: 23764760 DOI: 10.1097/CAD.0b013e3283635a47

There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by endophytic fungi from plants at the National Park, Pahang, Malaysia, were investigated. Five known compounds were identified using LC-UV-MS-NMR and they include trichodermol, 7-epi-brefeldin A, (3R,4S)-4-hydroxymellein, desmethyl-lasiodiplodin and cytochalasin D. The present study went on to investigate the potential anticancer effects of these compounds and the corresponding molecular mechanisms of the lead compound against human breast adenocarcinoma, MCF-7. For the preliminary screening, the cytotoxicity and apoptotic effects of these compounds against MCF-7 were examined. The compounds were also tested against noncarcinogenic hepatocytes (WRL68). The differential cytotoxicity was then determined using the MTT assay. Desmethyl-lasiodiplodin was found to suppress the growth of MCF-7, yielding an inhibitory concentration (IC50) that was seven-fold lower than that of the normal cells. The cytotoxic effect of desmethyl-lasiodiplodin was accompanied by apoptosis. Subsequent analysis demonstrated increased expression levels of caspase 3, c-myc and p53. Further, desmethyl-lasiodiplodin resulted in inhibition of monocyte chemotactic protein (MCP)-3, a cytokine involved in cell survival and metastasis. Hence, this study proposed that desmethyl-lasiodiplodin inhibited growth and survival of MCF-7 through the induction of apoptosis. This anticancer effect is mediated, in part, by upregulation of apoptotic genes and downregulation of MCP-3. As desmethyl-lasiodiplodin elicited minimal impact against normal hepatocytes, our findings also imply its potential use as a specific apoptotic agent in breast cancer treatment.

Matched MeSH terms: Inhibitory Concentration 50
Induction of apoptosis against cancer cell lines by four ascomycetes (endophytes) from Malaysian rainforest

Hazalin NA, Ramasamy K, Lim SM, Cole AL, Majeed AB

Phytomedicine, 2012 May 15;19(7):609-17.
PMID: 22397996 DOI: 10.1016/j.phymed.2012.01.007

Endophytic fungi have been shown to be a promising source of biologically active natural products. In the present study, extracts of four endophytic fungi isolated from plants of the National Park, Pahang were evaluated for their cytotoxic activity and the nature of their active compounds determined. Those extracts exhibiting activity with IC(50) values less than 17 μg/ml against HCT116, MCF-7 and K562 cell lines were shown to induce apoptosis in these cell lines. Molecular analysis, based on sequences of the rDNA internal transcribed spacers ITS1 and ITS4, revealed all four endophytic fungi to be ascomycetes: three sordariomycetes and a dothideomycete. Six known compounds, cytochalasin J, dechlorogriseofulvin, demethylharzianic-acid, griseofulvin, harzianic acid and 2-hexylidene-3-methyl-succinic acid were identified from a rapid dereplication technique for fungal metabolites using an in-house UV library. The results from the present study suggest the potential of endophytic fungi as cytotoxic agents, and there is an indication that the isolates contain bioactive compounds that mainly kill cancer cells by apoptosis.

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
Diaminobenzene schiff base, a novel class of DNA minor groove binder

Helal MH, Al-Mudaris ZA, Al-Douh MH, Osman H, Wahab HA, Alnajjar BO, et al.

Int J Oncol, 2012 Aug;41(2):504-10.
PMID: 22614449 DOI: 10.3892/ijo.2012.1491

Molecules that target the deoxyribonucleic acid (DNA) minor groove are relatively sequence specific and they can be excellent carrier structures for cytotoxic chemotherapeutic compounds which can help to minimize side effects. Two novel isomeric derivatives of diaminobenzene Schiff base [N,N'-bis (2-hydroxy-3-methoxybenzylidene)-1,2-diaminobenzene (2MJ) and N,N'-bis(2-hydroxy-3-methoxybenzylidene)-1,3-diaminobenzene (2MH)] were analyzed for their DNA minor groove binding (MGB) ability using viscometry, UV and fluorescence spectroscopy, computational modeling and clonogenic assay. The result shows that 2MJ and 2MH are strong DNA MGBs with the latter being more potent. 2MH can form interstrand hydrogen bond linkages at its oxygens with N3 of adenines. Changing the 2-hydroxy-3-methoxybenzylidene binding position to the 1,3 location on the diaminobenzene structure (2MJ) completely removed any viable hydrogen bond formation with the DNA and caused significant decrease in binding strength and minor groove binding potency. Neither compound showed any significant cytotoxicity towards human breast, colon or liver cancer cell lines.

Matched MeSH terms: Inhibitory Concentration 50
Langkolide, a 32-membered macrolactone antibiotic produced by Streptomyces sp. Acta 3062

Helaly SE, Kulik A, Zinecker H, Ramachandaran K, Tan GY, Imhoff JF, et al.

J Nat Prod, 2012 Jun 22;75(6):1018-24.
PMID: 22642587 DOI: 10.1021/np200580g

A new 32-membered macrolactone antibiotic, named langkolide, was isolated from the mycelium of Streptomyces sp. Acta 3062. The langkolide structure was determined by HR-MS and 1D and 2D NMR as a 32-membered macrolactone connected from an overhanging polyketide tail to a naphthoquinone unit mediated by two carbohydrate moieties. The producing strain was isolated from a rhizosphere soil of Clitorea sp. collected at Burau Bay, Langkawi, Malaysia, and was characterized by its morphological and chemotaxonomic features in addition to its 16S rRNA gene sequence. It was identified as a member of the Streptomyces galbus clade. Langkolide exhibited various bioactivities including antimicrobial and antiproliferative activities. Furthermore, langkolide inhibited human recombinant phosphodiesterase 4 with an IC(50) value of 0.48 μM.

Matched MeSH terms: Inhibitory Concentration 50
Fulltext Effectiveness of imatinib mesylate over etoposide in the treatment of sensitive and resistant chronic myeloid leukaemia cells in vitro

Husaini R, Ahmad M, Zakaria Z

Exp Ther Med, 2017 Jun;13(6):3209-3216.
PMID: 28587395 DOI: 10.3892/etm.2017.4443

Chronic myeloid leukaemia (CML) is a form of leukaemia derived from the myeloid cell lineage. Imatinib mesylate, the breakpoint cluster region-abelson murine leukeamia kinase inhibitor, is a specific reagent used in the clinical treatment of CML. The DNA topoisomerase II inhibitor, etoposide, is also employed as a therapeutic, though it is used to a lesser extent. The present study aims to evaluate the effects of CML-targeted therapy, utilising imatinib mesylate and etoposide in the in vitro treatment of parental sensitive and adriamycin-resistant CML in the K562 and K562/ADM cell lines, respectively. Preliminary work involved the screening of multidrug resistant (MDR) gene expression, including MDR1, MRP1 and B-cell lymphoma 2 (BCL-2) at the mRNA levels. The sensitive and resistant CML cell lines expressed the MRP1 gene, though the sensitive K562 cells expressed low, almost undetectable levels of MDR1 and BCL-2 genes relative to the K562/ADM cells. Following treatment with imatinib mesylate or etoposide, the IC50 for imatinib mesylate did not differ between the sensitive and resistant cell lines (0.492±0.024 and 0.378±0.029, respectively), indicating that imatinib mesylate is effective in the treatment of CML regardless of cell chemosensitivity. However, the IC50 for etoposide in sensitive K562 cells was markedly lower than that of K562/ADM cells (50.6±16.5 and 194±8.46 µM, respectively), suggesting that the higher expression levels of MDR1 and/or BCL-2 mRNA in resistant cells may be partially responsible for this effect. This is supported by terminal deoxynucleotidyl transferase dUTP nick-end labeling data, whereby a higher percentage of apoptotic cells were found in the sensitive and resistant K562 cells treated with imatinib mesylate (29.3±0.2 and 31.9±16.7%, respectively), whereas etoposide caused significant apoptosis of sensitive K562 cells (18.3±8.35%) relative to K562/ADM cells (5.17±3.3%). In addition, the MDR genes in K562/ADM cells were knocked down by short interfering RNAs. The percentage knockdowns were 15.4% for MRP1, 17.8% for MDR and 30.7% for BCL-2, which resulted in a non-significant difference in the half maximal inhibitory concentration value of K562/ADM cells relative to K562 cells upon treatment with etoposide.

Matched MeSH terms: Inhibitory Concentration 50

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