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Pink oyster mushroom Pleurotus flabellatus mycelium produced by an airlift bioreactor-the evidence of potent in vitro biological activities

Klaus A, Wan-Mohtar WAAQI, Nikolić B, Cvetković S, Vunduk J

World J Microbiol Biotechnol, 2021 Jan 04;37(1):17.
PMID: 33394203 DOI: 10.1007/s11274-020-02980-6

Four types of mycelial extracts were derived from the airlift liquid fermentation (ALF) of Pleurotus flabellatus, namely exopolysaccharide (EX), endopolysaccharide (EN), hot water (WE), and hot alkali (AE) extracts. Such extracts were screened for their active components and biological potential. EN proved to be most effective in inhibition of lipid peroxidation (EC50 = 1.71 ± 0.02 mg/mL) and in Cupric ion reducing antioxidant capacity (CUPRAC) assay (EC50 = 2.91 ± 0.01 mg TE/g). AE exhibited most pronounced ability to chelate ferrous ions (EC50 = 4.96 ± 0.08 mg/mL) and to scavenge ABTS radicals (EC50 = 3.36 ± 0.03 mg TE/g). β-glucans and total phenols contributed most to the chelating ability and quenching of ABTS radicals. Inhibition of lipid peroxidation correlated best with total glucans, total proteins, and β-glucans. Total proteins contributed most to CUPRAC antioxidant capacity. Antifungal effect was determined against Candida albicans ATCC 10231 (MIC: 0.019-0.625 mg/mL; MFC: 0.039-2.5 mg/mL), and towards C. albicans clinical isolate (MIC and MFC: 10.0-20.0 mg/mL). Comparison of cytotoxicity against colorectal carcinoma HCT 116 cells (IC50: 1.8 ± 0.3-24.6 ± 4.2 mg/mL) and normal lung MRC-5 fibroblasts (IC50: 17.0 ± 4.2-42.1 ± 6.1 mg/mL) showed that EN, and especially AE possess selective anticancer activity (SI values 3.41 and 9.44, respectively). Slight genotoxicity was observed only for AE and EX, indicating the low risk concerning this feature. Notable antioxidative and anticandidal activities, selective cytotoxicity against colorectal carcinoma cells, and absence/low genotoxicity pointed out that ALF-cultivated P. flabellatus mycelium could be considered as a valuable source of bioactive substances.

Matched MeSH terms: Cell Survival/drug effects
Designing the angiogenic inhibitor for brain tumor via disruption of VEGF and IL17A expression

Khan MS, Majid AM, Iqbal MA, Majid AS, Al-Mansoub M, Haque RS

Eur J Pharm Sci, 2016 Oct 10;93:304-18.
PMID: 27552907 DOI: 10.1016/j.ejps.2016.08.032

Glioblastoma multiforme is a highly malignant, heterogenic, and drug resistant tumor. The blood-brain barrier (BBB), systemic cytotoxicity, and limited specificity are the main obstacles in designing brain tumor drugs. In this study a computational approach was used to design brain tumor drugs that could downregulate VEGF and IL17A in glioblastoma multiforme type four. Computational screening tools were used to evaluate potential candidates for antiangiogenic activity, target binding, BBB permeability, and ADME physicochemical properties. Additionally, in vitro cytotoxicity, migration, invasion, tube formation, apoptosis, ROS and ELISA assays were conducted for molecule 6 that was deemed most likely to succeed. The efflux ratio of membrane permeability and calculated docking scores of permeability to glycoproteins (P-gps) were used to determine the BBB permeability of the molecules. The results showed BBB permeation for molecule 6, with the predicted efficiency of 0.55kcal/mol and binding affinity of -37kj/mol corresponding to an experimental efflux ratio of 0.625 and predicted -15kj/mol of binding affinity for P-gps. Molecule 6 significantly affected the angiogenesis pathways by 2-fold downregulation of IL17A and VEGF through inactivation of active sites of HSP90 (predicted binding: -37kj/mol, predicted efficiency: 0.55kcal/mol) and p23 (predicted binding: 12kj/mol, predicted efficiency: 0.17kcal/mol) chaperon proteins. Additionally, molecule 6 activated the 17.38% relative fold of ROS level at 18.3μg/mL and upregulated the caspase which lead the potential synergistic apoptosis through the antiangiogenic activity of molecule 6 and thereby the highly efficacious anticancer upshot. The results indicate that the binding of the molecules to the therapeutic target is not essential to produce a lethal effect on cancer cells of the brain and that antiangiogenic efficiency is much more important.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Anticancer and anti-inflammatory activities of girinimbine isolated from Murraya koenigii

Iman V, Mohan S, Abdelwahab SI, Karimian H, Nordin N, Fadaeinasab M, et al.

Drug Des Devel Ther, 2017;11:103-121.
PMID: 28096658 DOI: 10.2147/DDDT.S115135

Therapy that directly targets apoptosis and/or inflammation could be highly effective for the treatment of cancer. Murraya koenigii is an edible herb that has been traditionally used for cancer treatment as well as inflammation. Here, we describe that girinimbine, a carbazole alkaloid isolated from M. koenigii, induced apoptosis and inhibited inflammation in vitro as well as in vivo. Induction of apoptosis in human colon cancer cells (HT-29) by girinimbine revealed decreased cell viability in HT-29, whereas there was no cytotoxic effect on normal colon cells. Changes in mitochondrial membrane potential, nuclear condensation, cell permeability, and cytochrome c translocation in girinimbine-treated HT-29 cells demonstrated involvement of mitochondria in apoptosis. Early-phase apoptosis was shown in both acridine orange/propidium iodide and annexin V results. Girinimbine treatment also resulted in an induction of G0/G1 phase arrest which was further corroborated with the upregulation of two cyclin-dependent kinase proteins, p21 and p27. Girinimbine treatment activated apoptosis through the intrinsic pathway by activation of caspases 3 and 9 as well as cleaved caspases 3 and 9 which ended by triggering the execution pathway. Moreover, apoptosis was confirmed by downregulation of Bcl-2 and upregulation of Bax in girinimbine-treated cells. In addition, the key tumor suppressor protein, p53, was seen to be considerably upregulated upon girinimbine treatment. Induction of apoptosis by girinimbine was also evidenced in vivo in zebrafish embryos, with results demonstrating significant distribution of apoptotic cells in embryos after a 24-hour treatment period. Meanwhile, anti-inflammatory action was evidenced by the significant dose-dependent girinimbine inhibition of nitric oxide production in lipopolysaccharide/interferon-gamma-induced cells along with significant inhibition of nuclear factor-kappa B translocation from the cytoplasm to nucleus in stimulated RAW 264.7 cells. Girinimbine was also shown to have considerable antioxidant activity whereby 20 μg/mL of girinimbine was equivalent to 82.17±1.88 μM of Trolox. In mice with carrageenan-induced peritonitis, oral pretreatment with girinimbine helped limit total leukocyte migration (mainly of neutrophils), and reduced pro-inflammatory cytokine levels (interleukin-1beta and tumor necrosis factor-alpha) in the peritoneal fluid. These findings strongly suggest that girinimbine could act as a chemopreventive and/or chemotherapeutic agent by inducing apoptosis while suppressing inflammation. There is a potential for girinimbine to be further investigated for its applicability in treating early stages of cancer.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Kelussia odoratissima Mozaff. activates intrinsic pathway of apoptosis in breast cancer cells associated with S phase cell cycle arrest via involvement of p21/p27 in vitro and in vivo

Karimian H, Arya A, Fadaeinasab M, Razavi M, Hajrezaei M, Karim Khan A, et al.

Drug Des Devel Ther, 2017;11:337-350.
PMID: 28203057 DOI: 10.2147/DDDT.S121518

BACKGROUND: The aim of this study was to evaluate the anticancer potential of Kelussia odoratissima. Several in vitro and in vivo biological assays were applied to explore the direct effect of an extract and bioactive compound of this plant against breast cancer cells and its possible mechanism of action.
MATERIALS AND METHODS: K. odoratissima methanol extract (KME) was prepared, and MTT assay was used to evaluate the cytotoxicity. To identify the cytotoxic compound, a bioassay-guided investigation was performed on methanol extract. 8-Hydroxy-ar-turmerone was isolated as a bioactive compound. In vivo study was performed in the breast cancer rat model. LA7 cell line was used to induce the breast tumor. Histopathological and expression changes of PCNA, Bcl-2, Bax, p27 and p21 and caspase-3 were examined. The induction of apoptosis was tested using Annexin V-fluorescein isothiocyanate (FITC) assay. To confirm the intrinsic pathway of apoptosis, caspase-7 and caspase-9 assays were utilized. In addition, cell cycle arrest was evaluated.
RESULTS: Our results demonstrated that K. odoratissima has an obvious effect on the arrest of proliferation of cancer cells. It induced apoptosis, transduced the cell death signals, decreased the threshold of mitochondrial membrane potential (MMP), upregulated Bax and downregulated Bcl-2.
CONCLUSION: This study demonstrated that K. odoratissima exhibits antitumor activity against breast cancer cells via cell death and cell cycle arrest.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Development of erythropoietin receptor-targeted drug delivery system against breast cancer using tamoxifen-loaded nanostructured lipid carriers

Beh CY, How CW, Foo JB, Foong JN, Selvarajah GT, Rasedee A

Drug Des Devel Ther, 2017;11:771-782.
PMID: 28352153 DOI: 10.2147/DDDT.S123939

Tamoxifen (TAM) has been used in the treatment of breast cancers and is supplemented with erythropoietin (EPO) to alleviate the cancer-related anemia. The purported deleterious effects caused by the use of EPO with chemotherapeutic agents in the treatment of cancer-related anemia vary across studies and remain controversial. The use of nanoparticles as a drug delivery system has the potential to improve the specificity of anticancer drugs. In this study, we simultaneously incorporated two pharmacological active ingredients in one nanocarrier to develop EPO-conjugated TAM-loaded lipid nanoparticles (EPO-TAMNLC), a targeted delivery system, to enhance the cytotoxic activity while reducing the side effects of the ingredients. The effect of temperature in modulating the thermodynamic parameters associated with the binding of EPO and TAMNLC was assessed using isothermal titration calorimetry, while the unfolding of EPO structure was determined using fluorescence-quenching approach. The association efficiency of EPO and TAMNLC was 55.43%. Unlike binding of albumin to TAMNLC, the binding of EPO to TAMNLC occurred through endothermic and entropy-driven reaction. The EPO-TAMNLC formulation was stable because of the hydrophobic interaction and the high free energy, suggesting the spontaneity of the interactions between EPO and TAMNLC. The EPO-TAMNLC enhanced the in vitro cytotoxicity of TAM to MCF-7 cells. The EPO surface-functionalized TAMNLC could sequentially deliver EPO and TAM as well as improving site-specific delivery of these therapeutic compounds.

Matched MeSH terms: Cell Survival/drug effects
Copper supplementation amplifies the anti-tumor effect of curcumin in oral cancer cells

Lee HM, Patel V, Shyur LF, Lee WL

Phytomedicine, 2016 Nov 15;23(12):1535-1544.
PMID: 27765374 DOI: 10.1016/j.phymed.2016.09.005

BACKGROUND: Oral cancer is the sixth most common cancer worldwide and 90% of oral malignancies are caused by oral squamous cell carcinoma (OSCC). Curcumin, a phytocompound derived from turmeric (Curcuma longa) was observed to have anti-cancer activity which can be developed as an alternative treatment option for OSCC. However, OSCC cells with various clinical-pathological features respond differentially to curcumin treatment.
HYPOTHESIS: Intracellular copper levels have been reported to correlate with tumor pathogenesis and affect the sensitivity of cancer cells to cytotoxic chemotherapy. We hypothesized that intracellular copper levels may affect the sensitivity of oral cancer cells to curcumin.
METHODS: We analysed the correlation between intracellular copper levels and response to curcumin treatment in a panel of OSCC cell lines derived from oral cancer patients. Exogenous copper was supplemented in curcumin insensitive cell lines to observe the effect of copper on curcumin-mediated inhibition of cell viability and migration, as well as induction of oxidative stress and apoptosis. Protein markers of cell migration and oxidative stress were also analysed using Western blotting.
RESULTS: Concentrations of curcumin which inhibited 50% OSCC cell viability (IC50) was reduced up to 5 times in the presence of 250 µM copper. Increased copper level in curcumin-treated OSCC cells was accompanied by the induction of intracellular ROS and increased level of Nrf2 which regulates oxidative stress responses in cells. Supplemental copper also inhibited migration of curcumin-treated cells with enhanced level of E-cadherin and decreased vimentin, indications of suppressed epithelial-mesenchymal transition. Early apoptosis was observed in combined treatment but not in treatment with curcumin or copper alone.
CONCLUSION: Supplement of copper significantly enhanced the inhibitory effect of curcumin treatment on migration and viability of oral cancer cells. Together, these findings provide molecular insight into the role of copper in overcoming insensitivity of oral cancer cells to curcumin treatment, suggesting a new strategy for cancer therapy.

Matched MeSH terms: Cell Survival/drug effects
A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities

Bharkavi C, Vivek Kumar S, Ashraf Ali M, Osman H, Muthusubramanian S, Perumal S

Bioorg Med Chem, 2016 11 15;24(22):5873-5883.
PMID: 27687968 DOI: 10.1016/j.bmc.2016.09.044

A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 <1.56μM) and 6l (IC50=2.87μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16μmol/L respectively.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation

Tripathi M, Zhang CW, Singh BK, Sinha RA, Moe KT, DeSilva DA, et al.

Cell Death Dis, 2016 12 08;7(12):e2513.
PMID: 27929536 DOI: 10.1038/cddis.2016.374

Hyperhomocysteinemia (HHcy) is a well-known risk factor for stroke; however, its underlying molecular mechanism remains unclear. Using both mouse and cell culture models, we have provided evidence that impairment of autophagy has a central role in HHcy-induced cellular injury in the mouse brain. We observed accumulation of LC3B-II and p62 that was associated with increased MTOR signaling in human and mouse primary astrocyte cell cultures as well as a diet-induced mouse model of HHcy, HHcy decreased lysosomal membrane protein LAMP2, vacuolar ATPase (ATP6V0A2), and protease cathepsin D, suggesting that lysosomal dysfunction also contributed to the autophagic defect. Moreover, HHcy increased unfolded protein response. Interestingly, Vitamin B supplementation restored autophagic flux, alleviated ER stress, and reversed lysosomal dysfunction due to HHCy. Furthermore, the autophagy inducer, rapamycin was able to relieve ER stress and reverse lysosomal dysfunction caused by HHcy in vitro. Inhibition of autophagy by HHcy exacerbated cellular injury during oxygen and glucose deprivation and reperfusion (OGD/R), and oxidative stress. These effects were prevented by Vitamin B co-treatment, suggesting that it may be helpful in relieving detrimental effects of HHcy in ischemia/reperfusion or oxidative stress. Collectively, these findings show that Vitamin B therapy can reverse defects in cellular autophagy and ER stress due to HHcy; and thus may be a potential treatment to reduce ischemic damage caused by stroke in patients with HHcy.

Matched MeSH terms: Cell Survival/drug effects
Celastrol attenuates mitochondrial dysfunction and inflammation in palmitate-mediated insulin resistance in C3A hepatocytes

Abu Bakar MH, Sarmidi MR, Tan JS, Mohamad Rosdi MN

Eur J Pharmacol, 2017 Mar 15;799:73-83.
PMID: 28161417 DOI: 10.1016/j.ejphar.2017.01.043

Accumulating evidence indicates that mitochondrial dysfunction-induced inflammation is among the convergence points for the greatest hallmarks of hepatic insulin resistance. Celastrol, an anti-inflammatory compound from the root of Tripterygium Wilfordii has been reported to mitigate insulin resistance and inflammation in animal disease models. Nevertheless, the specific mechanistic actions of celastrol in modulating such improvements at the cellular level remain obscure. The present study sought to explore the mechanistic roles of celastrol upon insulin resistance induced by palmitate in C3A human hepatocytes. The hepatocytes exposed to palmitate (0.75mM) for 48h exhibited reduced both basal and insulin-stimulated glucose uptake, mitochondrial dysfunction, leading to increased mitochondrial oxidative stress with diminished fatty acid oxidation. Elevated expressions of nuclear factor-kappa B p65 (NF-κB p65), c-Jun NH(2)-terminal kinase (JNK) signaling pathways and the amplified release of pro-inflammatory cytokines including IL-8, IL-6, TNF-α and CRP were observed following palmitate treatment. Consistently, palmitate reduced and augmented phosphorylated Tyrosine-612 and Serine-307 of insulin receptor substrate-1 (IRS-1) proteins, respectively in hepatocytes. However, celastrol at the optimum concentration of 30nM was able to reverse these deleterious occasions and protected the cells from mitochondrial dysfunction and insulin resistance. Importantly, we presented evidence for the first time that celastrol efficiently prevented palmitate-induced insulin resistance in hepatocytes at least, via improved mitochondrial functions and insulin signaling pathways. In summary, the present investigation underlines a conceivable mechanism to elucidate the cytoprotective potential of celastrol in attenuating mitochondrial dysfunction and inflammation against the development of hepatic insulin resistance.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H2S-synthesizing enzymes

Gonzalez-Carter DA, Leo BF, Ruenraroengsak P, Chen S, Goode AE, Theodorou IG, et al.

Sci Rep, 2017 03 02;7:42871.
PMID: 28251989 DOI: 10.1038/srep42871

Silver nanoparticles (AgNP) are known to penetrate into the brain and cause neuronal death. However, there is a paucity in studies examining the effect of AgNP on the resident immune cells of the brain, microglia. Given microglia are implicated in neurodegenerative disorders such as Parkinson's disease (PD), it is important to examine how AgNPs affect microglial inflammation to fully assess AgNP neurotoxicity. In addition, understanding AgNP processing by microglia will allow better prediction of their long term bioreactivity. In the present study, the in vitro uptake and intracellular transformation of citrate-capped AgNPs by microglia, as well as their effects on microglial inflammation and related neurotoxicity were examined. Analytical microscopy demonstrated internalization and dissolution of AgNPs within microglia and formation of non-reactive silver sulphide (Ag2S) on the surface of AgNPs. Furthermore, AgNP-treatment up-regulated microglial expression of the hydrogen sulphide (H2S)-synthesizing enzyme cystathionine-γ-lyase (CSE). In addition, AgNPs showed significant anti-inflammatory effects, reducing lipopolysaccharide (LPS)-stimulated ROS, nitric oxide and TNFα production, which translated into reduced microglial toxicity towards dopaminergic neurons. Hence, the present results indicate that intracellular Ag2S formation, resulting from CSE-mediated H2S production in microglia, sequesters Ag+ ions released from AgNPs, significantly limiting their toxicity, concomitantly reducing microglial inflammation and related neurotoxicity.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Characterisation of sol-gel method synthesised MgZnFe2O4 nanoparticles and its cytotoxic effects on breast cancer cell line, MDA MB-231 in vitro

Nordin N, Kanagesan S, Zamberi NR, Yeap SK, Abu N, Tamilselvan S, et al.

IET Nanobiotechnol, 2017 Apr;11(3):343-348.
PMID: 28476993 DOI: 10.1049/iet-nbt.2016.0007

In this study, nanocrystalline magnesium zinc ferrite nanoparticles were successfully prepared by a simple sol-gel method using copper nitrate and ferric nitrate as raw materials. The calcined samples were characterised by differential thermal analysis/thermogravimetric analysis, Fourier transform infrared spectroscopy and X-ray diffraction. Transmission electron microscopy revealed that the average particle size of the calcined sample was in a range of 17-41 nm with an average of 29 nm and has spherical size. A cytotoxicity test was performed on human breast cancer cells (MDA MB-231) and (MCF-7) at various concentrations starting from (0 µg/ml) to (800 µg/ml). The sample possessed a mild toxic effect toward MDA MB-231 and MCF-7 after being examined with MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide) assay for up to 72 h of incubation. Higher reduction of cells viability was observed as the concentration of sample was increased in MDA MB-231 cell line than in MCF-7. Therefore, further cytotoxicity tests were performed on MDA MB-231 cell line.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Local ablation of gastric cancer by reconstituted apolipoprotein B lipoparticles carrying epigenetic drugs

Yang CL, Chao YJ, Wang HC, Hou YC, Chen CG, Chang CC, et al.

Nanomedicine, 2021 10;37:102450.
PMID: 34332115 DOI: 10.1016/j.nano.2021.102450

Epigenetic inhibitors have shown anticancer effects. Combination chemotherapy with epigenetic inhibitors has shown high effectiveness in gastric cancer clinical trials, but severe side effect and local progression are the causes of treatment failure. Therefore, we sought to develop an acidity-sensitive drug delivery system to release drugs locally to diminish unfavorable outcome of gastric cancer. In this study, we showed that, as compared with single agents, combination treatment with the demethylating agent 5'-aza-2'-deoxycytidine and HDAC inhibitors Trichostatin A or LBH589 decreased cell survival, blocked cell cycle by reducing number of S-phase cells and expression of cyclins, increased cell apoptosis by inducing expression of Bim and cleaved Caspase 3, and reexpressed tumor suppressor genes more effectively in MGCC3I cells. As a carrier, reconstituted apolipoprotein B lipoparticles (rABLs) could release drugs in acidic environments. Orally administrated embedded drugs not only showed inhibitory effects on gastric tumor growth in a syngeneic orthotopic mouse model, but also reduced the hepatic and renal toxicity. In conclusion, we have established rABL-based nanoparticles embedded epigenetic inhibitors for local treatment of gastric cancer, which have good therapeutic effects but do not cause severe side effects.

Matched MeSH terms: Cell Survival/drug effects
Water-Soluble Dioxidovanadium(V) Complexes of Aroylhydrazones: DNA/BSA Interactions, Hydrophobicity, and Cell-Selective Anticancer Potential

Sahu G, Banerjee A, Samanta R, Mohanty M, Lima S, Tiekink ERT, et al.

Inorg Chem, 2021 Oct 18;60(20):15291-15309.
PMID: 34597028 DOI: 10.1021/acs.inorgchem.1c01899

Five new anionic aqueous dioxidovanadium(V) complexes, [{VO2L1,2}A(H2O)n]α (1-5), with the aroylhydrazone ligands pyridine-4-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (H2L1) and furan-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (H2L2) incorporating different alkali metals (A = Na+, K+, Cs+) as countercation were synthesized and characterized by various physicochemical techniques. The solution-phase stabilities of 1-5 were determined by time-dependent NMR and UV-vis, and also the octanol/water partition coefficients were obtained by spectroscopic techniques. X-ray crystallography of 2-4 confirmed the presence of vanadium(V) centers coordinated by two cis-oxido-O atoms and the O, N, and O atoms of a dianionic tridentate ligand. To evaluate the biological behavior, all complexes were screened for their DNA/protein binding propensity through spectroscopic experiments. Finally, a cytotoxicity study of 1-5 was performed against colon (HT-29), breast (MCF-7), and cervical (HeLa) cancer cell lines and a noncancerous NIH-3T3 cell line. The cytotoxicity was cell-selective, being more active against HT-29 than against other cells. In addition, the role of hydrophobicity in the cytotoxicity was explained in that an optimal hydrophobicity is essential for high cytotoxicity. Moreover, the results of wound-healing assays indicated antimigration in case of HT-29 cells. Remarkably, 1 with an IC50 value of 5.42 ± 0.15 μM showed greater activity in comparison to cisplatin against the HT-29 cell line.

Matched MeSH terms: Cell Survival/drug effects
Biological evaluation the 2-aryl-2,3-dihydrobenzodiazaborinin-4(1H)-ones as potential dual α-glucosidase and α-amylase inhibitors with antioxidant properties

Mphahlele MJ, Magwaza NM, Malindisa ST, Choong YS

Chem Biol Drug Des, 2021 08;98(2):234-247.
PMID: 34013660 DOI: 10.1111/cbdd.13893

The 2-aryl-2,3-dihydrobenzodiazaborinin-4(1H)-ones (azaborininone) were synthesized as analogues of the 2-arylquinazoline-4-ones and screened through enzymatic assay in vitro for inhibitory effect against α-glucosidase and α-amylase activities. These azaborininones exhibited moderate to good inhibitory effect against these enzymes compared to acarbose used as a reference standard. The results are supported by the enzyme-ligand interactions through kinetics (in vitro) and molecular docking (in silico) studies. The test compounds also exhibited significant antioxidant activity through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) free radical scavenging assays. These azaborininone derivatives exhibited no effect on the viability of the human lung cancer (A549) cell line after 24 hr and were also not toxic towards the Vero cells.

Matched MeSH terms: Cell Survival/drug effects
Dichloromethane fraction of Moringa oleifera leaf methanolic extract selectively inhibits breast cancer cells (MCF7) by induction of apoptosis via upregulation of Bax, p53 and caspase 8 expressions

Mohd Fisall UF, Ismail NZ, Adebayo IA, Arsad H

Mol Biol Rep, 2021 May;48(5):4465-4475.
PMID: 34086162 DOI: 10.1007/s11033-021-06466-y

Moringa oleifera is a well-known medicinal plant which has anti-cancer and other biological activities. This research aims to determine the cytotoxic and apoptotic effect of M. oleifera leave extract on the breast cancer (MCF7) cells. The extracts were prepared using hexane, dichloromethane, chloroform and n-butanol by fractionating the crude 80% methanol extract of the plant leaves. The cytotoxic effect of the extracts on MCF7 cells were determined using CellTiter 96® AQueous One Solution Cell Proliferation (MTS) assay. The apoptosis study was conducted using Annexin V-FITC analysis and confirmed by Western blotting using selected proteins, which are p53, Bax, cytochrome c and caspase 8. Our results showed that the dichloromethane (DF-CME-MOL) extract was selectively cytotoxic to MCF7 cells (5 μg/mL) without significantly inhibiting the non-cancerous breast (MCF 10A) cells. It had the highest selectivity index (SI) value of 9.5 among the tested extracts. It also induced early apoptosis and increased the expressions of pro-apoptotic proteins Bax, caspase 8 and p53 in MCF7 cells. Gas chromatography-mass spectrometry analysis (GC-MS) analysis showed that the major compounds found in DF-CME-MOL were benzeneacetonitrile, 4-hydroxy- and benzeneacetic acid, 4-hydroxy-, methyl ester among others that were detected. Thus, DF-CME-MOL extract was found to inhibit the proliferation of MCF7 cells by apoptosis induction, which is likely due to the activities of the detected phytochemical compounds of the extract.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Graphene Oxide Loaded with Protocatechuic Acid and Chlorogenic Acid Dual Drug Nanodelivery System for Human Hepatocellular Carcinoma Therapeutic Application

Buskaran K, Hussein MZ, Moklas MAM, Masarudin MJ, Fakurazi S

Int J Mol Sci, 2021 May 28;22(11).
PMID: 34071389 DOI: 10.3390/ijms22115786

Hepatocellular carcinoma or hepatoma is a primary malignant neoplasm that responsible for 75-90% of all liver cancer in humans. Nanotechnology introduced the dual drug nanodelivery method as one of the initiatives in nanomedicine for cancer therapy. Graphene oxide (GO) loaded with protocatechuic acid (PCA) and chlorogenic acid (CA) have shown some anticancer activities in both passive and active targeting. The physicochemical characterizations for nanocomposites were conducted. Cell cytotoxicity assay and lactate dehydrogenase were conducted to estimate cell cytotoxicity and the severity of cell damage. Next, nanocomposite intracellular drug uptake was analyzed using a transmission electron microscope. The accumulation and localization of fluorescent-labelled nanocomposite in the human hepatocellular carcinoma (HepG2) cells were analyzed using a fluorescent microscope. Subsequently, Annexin V- fluorescein isothiocyanate (FITC)/propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Cell cycle arrest was ascertained at the G2/M phase. There was the depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. In conclusion, HepG2 cells treated with a graphene oxide-polyethylene glycol (GOP)-PCA/CA-FA dual drug nanocomposite exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid, chlorogenic acid and GOP-PCA/CA nanocomposite, may be due to the utilization of a folic acid-targeting nanodrug delivery system.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Growth inhibition of human gynecologic and colon cancer cells by Phyllanthus watsonii through apoptosis induction

Ramasamy S, Abdul Wahab N, Zainal Abidin N, Manickam S, Zakaria Z

PLoS One, 2012;7(4):e34793.
PMID: 22536331 DOI: 10.1371/journal.pone.0034793

Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC(50) values of ≤ 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10). PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC(50) values ranged from 0.66-0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs.

Matched MeSH terms: Cell Survival/drug effects
In vitro and in vivo anti-inflammatory activities of columbin through the inhibition of cycloxygenase-2 and nitric oxide but not the suppression of NF-κB translocation

Ibrahim Abdelwahab S, Syaed Koko W, Mohamed Elhassan Taha M, Mohan S, Achoui M, Ameen Abdulla M, et al.

Eur J Pharmacol, 2012 Mar 5;678(1-3):61-70.
PMID: 22227329 DOI: 10.1016/j.ejphar.2011.12.024

Columbin, a diterpenoid furanolactone, was isolated purely for the first time from the plant species Tinspora bakis. The anti-inflammatory effects of columbin were studied in vitro, in silico and in vivo. The effect of columbin on nitric oxide was examined on lipopolysaccharide-interferon-gamma (LPS/IFN) induced RAW264.7 macrophages. In vitro and in silico cyclooxygenase-1 and cyclooxygenase-2 inhibitory activities of columbin using biochemical kit and molecular docking, respectively, were investigated. Mechanism of columbin in suppressing NF-kappaB-translocation was tested using Cellomics®NF-κB activation assay and ArrayScan Reader in LPS-stimulated RAW264.7 cells. Moreover, effects of columbin in vivo that were done on carrageenan-induced mice paw-oedema were tested. Lastly, the in vitro and in vivo toxicities of columbin were examined on human liver cells and mice, respectively. Treatment with columbin or N(ω)-nitro-l-arginine methyl ester (l-NAME) inhibited LPS/IFN-γ-induced NO production without affecting the viability of RAW264.7. Pre-treatment of stimulated cells with columbin did not inhibit the translocation of NF-κB to the nucleus in LPS-stimulated cells. COX-1 and COX-2 inhibitory activities of columbin were 63.7±6.4% and 18.8±1.5% inhibition at 100μM, respectively. Molecular docking study further helped in supporting the observed COX-2 selectivity. Whereby, the interaction of columbin with Tyr385 and Arg120 signifies its higher activity in COX-2, as Tyr385 was reported to be involved in the abstraction of hydrogen from C-13 of arachidonate, and Arg120 is critical for high affinity arachidonate binding. Additionally, columbin inhibited oedema formation in mice paw. Lastly, the compound was observed to be safe in vitro and in vivo. This study presents columbin as a potential anti-inflammatory drug.

Matched MeSH terms: Cell Survival/drug effects
Fulltext In vitro cytotoxicity of Strobilanthes crispus ethanol extract on hormone dependent human breast adenocarcinoma MCF-7 cell

Chong HZ, Rahmat A, Yeap SK, Md Akim A, Alitheen NB, Othman F, et al.

BMC Complement Altern Med, 2012;12:35.
PMID: 22471785 DOI: 10.1186/1472-6882-12-35

Strobilanthes crispus has been traditionally used as antidiabetic, anticancer, diuretic, antilytic and laxative agent. However, cytotoxicity and antiproliferative effect of S. crispus is still unclear.

Matched MeSH terms: Cell Survival/drug effects
Characterization of anticancer, antimicrobial, antioxidant properties and chemical compositions of Peperomia pellucida leaf extract

Wei LS, Wee W, Siong JY, Syamsumir DF

Acta Med Iran, 2011;49(10):670-4.
PMID: 22071643

Peperomia pellucida leaf extract was characterized for its anticancer, antimicrobial, antioxidant activities, and chemical compositions. Anticancer activity of P. pellucida leaf extract was determined through Colorimetric MTT (tetrazolium) assay against human breast adenocarcinoma (MCF-7) cell line and the antimicrobial property of the plant extract was revealed by using two-fold broth micro-dilution method against 10 bacterial isolates. Antioxidant activity of the plant extract was then characterized using α, α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging method and the chemical compositions were screened and identified using gas chromatography-mass spectrometry (GC-MS). The results of present study indicated that P. pellucida leaf extract possessed anticancer activities with half maximal inhibitory concentration (IC(50)) of 10.4 ± 0.06 µg/ml. The minimum inhibitory concentration (MIC) values were ranged from 31.25 to 125 mg/l in which the plant extract was found to inhibit the growth of Edwardsiella tarda, Escherichia coli, Flavobacterium sp., Pseudomonas aeruginosa and Vibrio cholerae at 31.25 mg/l; Klebsiella sp., Aeromonas hydrophila and Vibrio alginolyticus at 62.5 mg/l; and it was able to control the growth of Salmonella sp. and Vibrio parahaemolyticus at 125 mg/l. At the concentration of 0.625 ppt, the plant extract was found to inhibit 30% of DPPH, free radical. Phytol (37.88%) was the major compound in the plant extract followed by 2-Naphthalenol, decahydro- (26.20%), Hexadecanoic acid, methyl ester (18.31%) and 9,12-Octadecadienoic acid (Z,Z)-, methyl ester (17.61%). Findings from this study indicated that methanol extract of P. pellucida leaf possessed vast potential as medicinal drug especially in breast cancer treatment.

Matched MeSH terms: Cell Survival/drug effects

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