scholarly journals Anticancer Potential of Biogenic Silver Nanoparticles: A Mechanistic Study

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 707
Author(s):  
Mohd Shahnawaz Khan ◽  
Alya Alomari ◽  
Shams Tabrez ◽  
Iftekhar Hassan ◽  
Rizwan Wahab ◽  
...  

The continuous loss of human life due to the paucity of effective drugs against different forms of cancer demands a better/noble therapeutic approach. One possible way could be the use of nanostructures-based treatment methods. In the current piece of work, we have synthesized silver nanoparticles (AgNPs) using plant (Heliotropiumbacciferum) extract using AgNO3 as starting materials. The size, shape, and structure of synthesized AgNPs were confirmed by various spectroscopy and microscopic techniques. The average size of biosynthesized AgNPs was found to be in the range of 15 nm. The anticancer potential of these AgNPs was evaluated by a battery of tests such as MTT, scratch, and comet assays in breast (MCF-7) and colorectal (HCT-116) cancer models. The toxicity of AgNPs towards cancer cells was confirmed by the expression pattern of apoptotic (p53, Bax, caspase-3) and antiapoptotic (BCl-2) genes by RT-PCR. The cell viability assay showed an IC50 value of 5.44 and 9.54 µg/mL for AgNPs in MCF-7 and HCT-116 cell lines respectively. We also observed cell migration inhibiting potential of AgNPs in a concentration-dependent manner in MCF-7 cell lines. A tremendous rise (150–250%) in the production of ROS was observed as a result of AgNPs treatment compared with control. Moreover, the RT-PCR results indicated the difference in expression levels of pro/antiapoptotic proteins in both cancer cells. All these results indicate that cell death observed by us is mediated by ROS production, which might have altered the cellular redox status. Collectively, we report the antimetastasis potential of biogenic synthesized AgNPs against breast and colorectal cancers. The biogenic synthesis of AgNPs seems to be a promising anticancer therapy with greater efficacy against the studied cell lines.

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2099 ◽  
Author(s):  
Reham Samir Hamida ◽  
Gadah Albasher ◽  
Mashael Mohammed Bin-Meferij

Green nanoparticles represent a revolution in bionanotechnology, providing opportunities to fight life-threatening diseases, such as cancer, with less risk to the environment and to human health. Here, for the first time, we systematically investigated the anticancer activity and possible mechanism of novel silver nanoparticles (N-SNPs) synthesized by Nostoc Bahar M against the MCF-7 breast cancer cells, HCT-116 colorectal adenocarcinoma cells, and HepG2 liver cancer cells, using cell viability assays, morphological characterization with inverted light and transmission electron microscopy, antioxidants and enzymes (glutathione peroxidase (GPx), glutathione (GSH), adenosine triphosphatase (ATPase), and lactate dehydrogenase (LDH)), and western blotting (protein kinase B (Akt), phosphorylated-Akt (p-Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma 2 (Bcl-2), tumor suppressor (p53), and caspase 3). N-SNPs decreased the viability of MCF-7, HCT-116, and HepG2 cells, with half-maximal inhibitory concentrations of 54, 56, and 80 µg/mL, respectively. They also significantly increased LDH leakage, enhanced oxidative stress via effects on antioxidative markers, and caused metabolic stress by significantly decreasing ATPase levels. N-SNPs caused extensive ultrastructural alterations in cell and nuclear structures, as well as in various organelles. Furthermore, N-SNPs triggered apoptosis via the activation of caspase 3 and p53, and suppressed the mTOR signaling pathway via downregulating apoptosis-evading proteins in MCF-7, HCT-116, and HepG2 cells. Ultrastructural analysis, together with biochemical and molecular analyses, revealed that N-SNPs enhanced apoptosis via the induction of oxidative stress and/or through direct interactions with cellular structures in all tested cells. The cytotoxicity of Nostoc-mediated SNPs represents a new strategy for cancer treatment via targeting various cell death pathways. However, the potential of N-SNPs to be usable and biocompatible anticancer drug will depend on their toxicity against normal cells.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Natalia Lemos Chaves ◽  
Danilo Aquino Amorim ◽  
Cláudio Afonso Pinho Lopes ◽  
Irina Estrela-Lopis ◽  
Julia Böttner ◽  
...  

Abstract Background Nanocarriers have the potential to improve the therapeutic index of currently available drugs by increasing drug efficacy, lowering drug toxicity and achieving steady-state therapeutic levels of drugs over an extended period. The association of maghemite nanoparticles (NPs) with rhodium citrate (forming the complex hereafter referred to as MRC) has the potential to increase the specificity of the cytotoxic action of the latter compound, since this nanocomposite can be guided or transported to a target by the use of an external magnetic field. However, the behavior of these nanoparticles for an extended time of exposure to breast cancer cells has not yet been explored, and nor has MRC cytotoxicity comparison in different cell lines been performed until now. In this work, the effects of MRC NPs on these cells were analyzed for up to 72 h of exposure, and we focused on comparing NPs’ therapeutic effectiveness in different cell lines to elect the most responsive model, while elucidating the underlying action mechanism. Results MRC complexes exhibited broad cytotoxicity on human tumor cells, mainly in the first 24 h. However, while MRC induced cytotoxicity in MDA-MB-231 in a time-dependent manner, progressively decreasing the required dose for significant reduction in cell viability at 48 and 72 h, MCF-7 appears to recover its viability after 48 h of exposure. The recovery of MCF-7 is possibly explained by a resistance mechanism mediated by PGP (P-glycoprotein) proteins, which increase in these cells after MRC treatment. Remaining viable tumor metastatic cells had the migration capacity reduced after treatment with MRC (24 h). Moreover, MRC treatment induced S phase arrest of the cell cycle. Conclusion MRC act at the nucleus, inhibiting DNA synthesis and proliferation and inducing cell death. These effects were verified in both tumor lines, but MDA-MB-231 cells seem to be more responsive to the effects of NPs. In addition, NPs may also disrupt the metastatic activity of remaining cells, by reducing their migratory capacity. Our results suggest that MRC nanoparticles are a promising nanomaterial that can provide a convenient route for tumor targeting and treatment, mainly in metastatic cells.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Chhavi Sharma ◽  
Andrea J. Vas ◽  
Payal Goala ◽  
Taher M. Gheewala ◽  
Tahir A. Rizvi ◽  
...  

The present study was designed to gain insight into the antiproliferative activity of ethanolic neem leaves extract (ENLE) alone or in combination with cisplatin by cell viability assay on human breast (MCF-7) and cervical (HeLa) cancer cells. Nuclear morphological examination and cell cycle analysis were performed to determine the mode of cell death. Further, to identify its molecular targets, the expression of genes involved in apoptosis, cell cycle progression, and drug metabolism was analyzed by RT-PCR. Treatment of MCF-7, HeLa, and normal cells with ENLE differentially suppressed the growth of cancer cells in a dose- and time-dependent manner through apoptosis. Additionally, lower dose combinations of ENLE with cisplatin resulted in synergistic growth inhibition of these cells compared to the individual drugs (combination index <1). ENLE significantly modulated the expression of bax, cyclin D1, and cytochrome P450 monooxygenases (CYP 1A1 and CYP 1A2) in a time-dependent manner in these cells. Conclusively, these results emphasize the chemopreventive ability of neem alone or in combination with chemotherapeutic treatment to reduce the cytotoxic effects on normal cells, while potentiating their efficacy at lower doses. Thus, neem may be a prospective therapeutic agent to combat gynecological cancers.


2020 ◽  
Vol 13 (6) ◽  
pp. 115 ◽  
Author(s):  
Waseem El-Huneidi ◽  
Naglaa G. Shehab ◽  
Khuloud Bajbouj ◽  
Arya Vinod ◽  
Ahmed El-Serafi ◽  
...  

Micromeria fruticosa (L.) Druce subsp. serpyllifolia (Lamiaceae) has been used widely in folk medicine to alleviate various ailments such as abdominal pains, diarrhea, colds, eye infections, heart disorders and wounds. A few reports have confirmed different therapeutic potentialities of its extracts, including the anti-inflammatory, gastroprotective, analgesic, antiobesity and antidiabetic activities. This study aimed to investigate the mechanistic pathway of the antiproliferative activity of the ethanolic extract of M. fruticosa on two different cancer cell lines, namely human breast (mammary carcinoma F7 (MCF-7)) and human colorectal (human colon tumor cells (HCT-116)) cell lines. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay, Annexin V-FITC/PI, caspases 8/9 and cell cycle analyses, qRT-PCR and Western blot were used to assess the effect of M. fruticosa on cytotoxicity, apoptosis, cell cycle, cell cycle-related genes and protein expression profiles in MCF-7 and HCT-116. The extract inhibits cell proliferation in a time- and dose-dependent manner. The half-maximal inhibitory concentration (IC50) for both cell lines was found to be 100 μg/mL. Apoptosis induction was confirmed by Annexin V-FITC/PI, that was related to caspases 8 and 9 activities induction. Furthermore, the cell cycle analysis revealed arrest at G2/M phase. The underlying mechanism involved in the G2/M arrest was found to be associated with the downregulation of CDK1, cyclin B1 and survivin that was confirmed by qRT-PCR and Western blotting.


Genetika ◽  
2018 ◽  
Vol 50 (2) ◽  
pp. 647-657
Author(s):  
Iman Shahrokhiyan ◽  
Abbas Doosti ◽  
Hossein Sazegar

The effects of amygdalin as an herbal substance on prevention of cancer cells proliferation it has been shown. Also, survivin gene is one of the important genes on inhibition of apoptosis and controlling of the cell cycle in cancer cell lines. For this purpose, the present study was undertaken for the first time to evaluate the effects of amygdalin on survivin gene expression in MCF-7 and HDF. The MCF-7 (Breast cancer cells) and normal HDF were treated by different doses of amygdalin (0.5 to 10 mg/ml). Then, the MTT assay was done on each cell groups on 24, 48, and 72 h after treatment. In each period time the cells were detached and used for RNA extraction and cDNA synthesis. Finally, the survivin gene expression in each cell groups was evaluated by quantitative real-time PCR (q-RT-PCR) analysis. The MTT assay was showed that 5 mg/ml of amygdalin concentration at 48 hours after treatment it was suitable for evaluation of this compound on MCF-7 and HDF cell lines. The survey results of q-RT-PCR were showed in both amygdalin-treated MCF-7 (MCF-7+AMG) compare to the treated HDF (HDF-AMG as an control group) the expression level of survivin gene were decreased but this reduction only in MCF-7+AMG group was statistically significant (p <0.05). Our findings indicated that amygdalin in particular; decrease the survivin mRNA in MCF-7 breast cancer cells compare to normal healthy cells and leads to apoptosis and the death of cancer cells. It is suggested that in future study it must be better the effects of amygdalin supplemented with surfactant investigate against other cancer cells and evaluate the more molecular markers to specify the anti-cancer activity potential of this herbal compound.


2019 ◽  
Vol 20 (10) ◽  
pp. 804-814 ◽  
Author(s):  
Bing Wang ◽  
Yuzhu Zhang ◽  
Meina Ye ◽  
Jingjing Wu ◽  
Lina Ma ◽  
...  

Background: Chemoresistance blunts the therapeutic effect of cisplatin (DDP) on Triple-Negative Breast Cancer (TNBC). Researchers have not determined to date whether exosomes confer DDP resistance to other breast cancer cells or whether exosomal transfer of miRNAs derived from DDP-resistant TNBC cells confer DDP resistance. Objective: The aim of this study was to investigate the role of exosomes in chemoresistance in breast cancer. Methods: MDA-MB-231 cells resistant to DDP (231/DDP) were established. Exosomes were isolated from 231/DDP cells (DDP/EXO) and characterized by measuring the levels of protein markers, nanoparticle tracking analysis and transmission electron microscopy. MDA-MB-231, MCF-7 and SKBR-3 cell lines were treated with the isolated DDP/EXOs and cell proliferation and cytotoxicity to DDP were evaluated using MTT assays and apoptosis analyses. Western blotting was used to examine P-glycoprotein (P-gp) expression. Additionally, a microarray was used to analyse microRNA (miRNA) expression profiles in MDA-MB-231 and 231/DDP exosomes. The effects on miRNAs were determined using RT-PCR. Exosomal miR-423-5p was extracted, and differential expression was verified. The MTT cell viability assay, flow cytometry, and Transwell and immunofluorescence assays were performed to determine if differential expression of miR-423-5p sensitized cells to DDP in vitro. Results: Under a transmission electron microscope, the isolated exosomes exhibited a round or oval shape with a diameter ranging between 40 and 100 nm. DDP/EXOs labelled with PKH67 were taken up by MDA-MB-231 cells. After an incubation with DDP/EXOs, the cell lines exhibited a higher IC50 value for cisplatin, P-gp expression, migration and invasion capabilities and a lower apoptosis rate. Furthermore, 60 miRNAs from exosomes derived from 231/DDP cells were significantly up-regulated compared to exosomes from MDA-MB-231 cells. Notably, compared to the corresponding sensitive exosomes, miR-370-3p, miR-423-5p and miR-373 were the most differentially expressed miRNAs in DDP-resistant exosomes. We chose miR-423-5p, and up-regulation and down-regulation of exosomal miR-423-5p expression significantly affected DDP resistance. Conclusions: Exosomes from DDP-resistant TNBC cells (231/DDP) altered the sensitivity of other breast cancer cells to DDP in an exosomal miR-423-5p dependent manner. Our research helps to elucidate the mechanism of DDP resistance in breast cancer.


2019 ◽  
Vol 12 (6) ◽  
pp. 7-16
Author(s):  
Annie Aglin A ◽  
P Shruthi ◽  
S Subathra

Biosynthesized nanoparticles have many applications in the field of biopharmaceutics due to its high surface to volume ratio, less toxicity and synergistic effects with conjugated biomolecules. This study reports the selective cytotoxicity effect of biosynthesized silver nanoparticles (AgNPs) on breast cancer cell lines MCF-7 and MDA MB-231. AgNPs were synthesized using an aqueous extract of Mollugo cerviana species of plant and characterized using UV–visible spectroscopy, zeta potential analyser, SEM, FT-IR, XRD, and EDX. An UV-visible spectrum of the extract shows the surface plasmon resonance peak of AgNPs at 420 nm. SEM analysis results confirm the sphericity of the AgNPs whose size isin the range of 50 – 100 nm. The zeta potential value of -27 mV indicates the stability of the biosynthesized AgNPs. Dose-Dependent cytotoxicity was observed against human breast cancer cells lines MCF-7 and MDA MB-231. The inhibitory concentrations (IC50) are 21.53 μg/mL and 25.52 μg/mL respectively. There was no significant toxicity against Vero cells below 100 μg/mL concentration of AgNPs. The data obtained in the study reveal the potential therapeutic value of biogenic silver nanoparticles in cancer treatment and further studies are required to elucidate the mechanism of selective activity of biosynthesized AgNPs on cancer cells.


2021 ◽  
Author(s):  
Daniel Pereira Maurício de Barros ◽  
Ayla Nóbrega André ◽  
Basak Aru ◽  
Turkay Simsek ◽  
Gulderen Yanikkaya Demirel

Abstract With the emergence of Molecular Targeted Therapy, the interest in studying immunogenetic components that act in carcinogenesis has grown. The role of the estrogen receptor (ER) in initiation and progression of breast cancer is well documented and the estrogen treatment may affect expression of proteins described as tumor stem cell biomarkers in estrogen-sensitive breast cancer. The aim of this study is to analyze the expression of CD44 and CD326 on MCF-7 (ER+) and MDA-MB-231 (ER-) cell lines treated with 17β-estradiol for different periods. Our results indicate that 17β-estradiol can modulate CD44 and CD326 expression in breast cancer cells that have functional estrogen receptors in a time dependent manner. To our knowledge, this is the first study to investigate the influence of 17β-estradiol on CD44 and CD326 expression in MCF-7 and MDA-MB-231 cell lines. Further investigations with primary patient samples and their cultures will enhance our knowledge on the effect of hormones on breast cancer.


2019 ◽  
Vol 10 (4) ◽  
pp. 3236-3243 ◽  
Author(s):  
Masese Osoro Brian ◽  
Selvi S

In this study, we assessed the biological effect of Ceiba pentandra bark silver nanoparticles (CP-AgNPs) on HCT-116 cancer cells with an emphasis on cell cytotoxicity, quantification of ROS and determination of mitochondria membrane potential.  The synthesized Ceiba pentandra bark silver nanoparticles were characterized by UV-vis spectrometer, High-resolution transmission electron microscope (HR-TEM), X-ray diffraction (XRD) and Selected area electron diffraction (SAED). The synthesized silver nanoparticle cytotoxic and apoptotic effects were studied on colorectal cancer cells (HCT-116). The nanoparticles exhibited an inhibitory concentration (IC50) at (60μg/mL). CP-AgNPs significantly inhibited cell viability and changed the morphology of HCT-116 colon cancer cells. Moreover, CP-AgNPs increased the level of reactive oxygen species, induced cell apoptosis in HCT-116 cell lines through the interference of the mitochondrial membrane potential. These results indicated that Ceiba pentandra bark silver nanoparticles (CP-AgNPs) might act as prospective anticancer agents in colon cancer cells.


2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Syarifah Nur Syed Abdul Rahman ◽  
Norhanom Abdul Wahab ◽  
Sri Nurestri Abd Malek

Bioassay-guided isolation of the active hexane fractions ofCurcuma zedoarialed to the identification of five pure compounds, namely, curzerenone (1), neocurdione (2), curdione (3), alismol (4), and zederone (5) and a mixture of sterols, namely, campesterol (6), stigmasterol (7), andβ-sitosterol (8). Alismol has never been reported to be present inCurcuma zedoaria. All isolated compounds except (3) were evaluated for their cytotoxic activity against MCF-7, Ca Ski, and HCT-116 cancer cell lines and noncancer human fibroblast cell line (MRC-5) using neutral red cytotoxicity assay. Curzerenone and alismol significantly inhibited cell proliferation in human cancer cell lines MCF-7, Ca Ski, and HCT-116 in a dose-dependent manner. Cytological observations by an inverted phase contrast microscope and Hoechst 33342/PI dual-staining assay showed typical apoptotic morphology of cancer cells upon treatment with curzerenone and alismol. Both compounds induce apoptosis through the activation of caspase-3. It can thus be suggested that curzerenone and alismol are modulated by apoptosis via caspase-3 signalling pathway. The findings of the present study support the use ofCurcuma zedoariarhizomes in traditional medicine for the treatment of cancer-related diseases. Thus, two naturally occurring sesquiterpenoids, curzerenone and alismol, hold great promise for use in chemopreventive and chemotherapeutic strategies.


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