Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 37-55
Author(s):  
Yahaya Gavamukulya ◽  
Esther N. Maina ◽  
Hany A. El-Shemy ◽  
Amos M. Meroka ◽  
Geoffrey K. Kangogo ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Anticancer Drugs ◽  
Hela Cells ◽  
Selectivity Index ◽  
Annona Muricata ◽  
Anticancer Activities ◽  
Apoptosis Pathway ◽  
Migration Assay ◽  
Intrinsic Apoptosis Pathway ◽  
In Cells

BACKGROUND: Green synthesized nanoparticles have been earmarked for use in nanomedicine including for the development of better anticancer drugs. OBJECTIVE: The aim of this study was to undertake biochemical evaluation of anticancer activities of green synthesized silver nanoparticles (AgNPs) from ethanolic extracts of fruits (AgNPs-F) and leaves (AgNPs-L) of Annona muricata. METHODS: Previously synthesized silver nanoparticles were used for the study. The effects of the AgNPs and 5-Fluorouracil were studied on PC3, HeLa and PNT1A cells. The resazurin, migration and colonogenic assays as well as qRT-PCR were employed. RESULTS: The AgNPs-F displayed significant antiproliferative effects against HeLa cells with an IC50 of 38.58μg/ml and PC3 cells with an IC50 of 48.17μg/ml but selectively spared normal PNT1A cells (selectivity index of 7.8), in comparison with first line drug 5FU and AgNPs-L whose selectivity index were 3.56 and 2.26 respectively. The migration assay revealed potential inhibition of the metastatic activity of the cells by the AgNPs-F while the colonogenic assay indicated the permanent effect of the AgNPs-F on the cancer cells yet being reversible on the normal cells in contrast with 5FU and AgNPs-L. CASP9 was significantly over expressed in all HeLa cells treated with the AgNPs-F (1.53-fold), AgNPs-L (1.52-fold) and 5FU (4.30-fold). CXCL1 was under expressed in HeLa cells treated with AgNPs-F (0.69-fold) and AgNPs-L (0.58-fold) and over expressed in cells treated with 5FU (4.95-fold), but the difference was not statistically significant. CXCR2 was significantly over expressed in HeLa cells treated with 5FU (8.66-fold) and AgNPs-F (1.12-fold) but under expressed in cells treated with AgNPs-L (0.76-fold). CONCLUSIONS: Here we show that biosynthesized AgNPs especially AgNPs-F can be used in the development of novel and better anticancer drugs. The mechanism of action of the AgNPs involves activation of the intrinsic apoptosis pathway through upregulation of CASP9 and concerted down regulation of the CXCL1/ CXCR2 gene axis.

scholarly journals Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Teng-Long Han ◽  
Hang Sha ◽  
Jun Ji ◽  
Yun-Tian Li ◽  
Deng-Shan Wu ◽  
...  
Keyword(s):  
Hela Cells ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Clonogenic Survival ◽  
Mitotic Arrest ◽  
Apoptosis Pathway ◽  
Mitotic Slippage ◽  
Intrinsic Apoptosis Pathway ◽  
Apoptosis Protein ◽  
Induced Apoptosis

AbstractThe anticancer effects of taxanes are attributed to the induction of mitotic arrest through activation of the spindle assembly checkpoint. Cell death following extended mitotic arrest is mediated by the intrinsic apoptosis pathway. Accordingly, factors that influence the robustness of mitotic arrest or disrupt the apoptotic machinery confer drug resistance. Survivin is an inhibitor of apoptosis protein. Its overexpression is associated with chemoresistance, and its targeting leads to drug sensitization. However, Survivin also acts specifically in the spindle assembly checkpoint response to taxanes. Hence, the failure of Survivin-depleted cells to arrest in mitosis may lead to taxane resistance. Here we show that Survivin depletion protects HeLa cells against docetaxel-induced apoptosis by facilitating mitotic slippage. However, Survivin depletion does not promote clonogenic survival of tumor cells but increases the level of cellular senescence induced by docetaxel. Moreover, lentiviral overexpression of Survivin does not provide protection against docetaxel or cisplatin treatment, in contrast to the anti-apoptotic Bcl-xL or Bcl-2. Our findings suggest that targeting Survivin may influence the cell response to docetaxel by driving the cells through aberrant mitotic progression, rather than directly sensitizing cells to apoptosis.

scholarly journals Optimization of PhysicoChemical Parameters for Production of Cytotoxic Secondary Metabolites and Apoptosis Induction Activities in the Culture Extract of a Marine Algal–Derived Endophytic Fungus Aspergillus sp.

2021 ◽  
Vol 12 ◽  
Author(s):  
Sidhartha Taritla ◽  
Madhuree Kumari ◽  
Siya Kamat ◽  
Sarita G. Bhat ◽  
C. Jayabaskaran
Keyword(s):  
Secondary Metabolites ◽  
Cell Lines ◽  
Cancer Cell ◽  
Hela Cells ◽  
Physicochemical Parameters ◽  
Cancer Cell Lines ◽  
Apoptosis Induction ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway ◽  
Pharmacologically Active

The endophytic fungal community in the marine ecosystem has been demonstrated to be relevant source of novel and pharmacologically active secondary metabolites. The current study focused on the evaluation of cytotoxic and apoptosis induction potential in the culture extracts of endophytic fungi associated with Sargassum muticum, a marine brown alga. The cytotoxicity of the four marine endophytes, Aspergillus sp., Nigrospora sphaerica, Talaromyces purpureogenus, and Talaromyces stipitatus, was evaluated by the MTT assay on HeLa cells. Further, several physicochemical parameters, including growth curve, culture media, and organic solvents, were optimized for enhanced cytotoxic activity of the selected extract. The Aspergillus sp. ethyl acetate extract (ASE) showed maximum cytotoxicity on multiple cancer cell lines. Chemical investigation of the metabolites by gas chromatography–mass spectroscopy (GC-MS) showed the presence of several compounds, including quinoline, indole, 2,4-bis(1,1-dimethylethyl) phenol, and hexadecenoic acid, known to be cytotoxic in ASE. The ASE was then tested for cytotoxicity in vitro on a panel of six human cancer cell lines, namely, HeLa (cervical adenocarcinoma), MCF-7 (breast adenocarcinoma), Hep G2 (hepatocellular carcinoma), A-549 (lung carcinoma), A-431 (skin/epidermis carcinoma), and LN-229 (glioblastoma). HeLa cells were most vulnerable to ASE treatment with an IC50 value of 24 ± 2 μg/ml. The mechanism of cytotoxicity exhibited by the ASE was further investigated on Hela cells. The results showed that the ASE was capable of inducing apoptosis in HeLa cells through production of reactive oxygen species, depolarization of mitochondrial membrane, and activation of the caspase-3 pathway, which shows a possible activation of the intrinsic apoptosis pathway. It also arrested the HeLa cells at the G2/M phase of the cell cycle, eventually leading to apoptosis. Through this study, we add to the knowledge about the marine algae associated with fungal endophytes and report its potential for purifying specific compounds responsible for cytotoxicity.

Valproic Acid Induces Non Apoptotic Cell Death in Myeloma Cells and Cell Lines.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5130-5130
Author(s):  
Chantal Schwartz ◽  
Valérie Palissot ◽  
Rene I. Brons ◽  
Bernadette Leners ◽  
Manon Bosseler ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Multiple Myeloma ◽  
Valproic Acid ◽  
Cell Death ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Signal Transduction Pathways ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway ◽  
In Cells

Abstract Multiple myeloma is, despite the emergence of new treatment strategies in recent years, still a lethal disease in 2005. Over the last several years, significant insights into the dysregulation of various signal transduction pathways of MM have emerged and have evolved the development of new agents. Histone deacetylase inhibitors as valproic acid are compounds that inhibit HDACs enzymes that, in conjunction with histone acetylases, regulate the acetylation state of histones and, by extension, the conformational status of chromatin. VPA is clinically known to be used in treatment of different types of epileptic disease. Effects and signal transduction pathways of cell death have been studied in cells harvested and purified from routine bone marrow aspirates of several patients with multiple myeloma, as well as on myeloma cell lines (OPM2, U266) treated with a physiologic dose range of valproic acid (1–4 mM). We observe significant in vitro toxicity starting at doses of 1 mM for 24h in cell lines as well as in patient cells using an XTT based cytotoxicity assay. The question we adressed was the mechanisms by which the MM died. Flow cytometric analysis with PI / Annexin V staining does not show apoptosis features, nor do TUNEL staining or DNA fragmentation assays, suggesting non activation of the intrinsic apoptosis pathway. In contrast, cell morphology of treated cells stained with May-Gruenwald-Giemsa staining show increase in multinucleated giant cells. Multinucleation has often been described in cells which die through mitotic catastrophe. Further experiments exploring this hypothesis will be conducted. Effect of 48h valproic ac on myeloma cell lines Effect of 48h valproic ac on myeloma cell lines Effect of 48h valproic ac on CD138 cells from myeloma patients Effect of 48h valproic ac on CD138 cells from myeloma patients

Polymeric Silver Nanoparticles: Potential for Folate-Targeted Delivery of Cisplatin In Vitro

2021 ◽  
Author(s):  
Radhini Veerappan ◽  
Aliscia Daniels ◽  
Moganavelli Singh
Keyword(s):  
Silver Nanoparticles ◽  
Side Effects ◽  
Cancer Therapy ◽  
Hela Cells ◽  
Targeted Delivery ◽  
Folate Receptor ◽  
Breast Adenocarcinoma ◽  
Anticancer Activities

Nanotechnology is a favorable avenue for improving therapeutic strategies, especially in cancer therapy. The harmful side effects of traditional cancer therapy impact dramatically on the patient’s quality of life. Cisplatin, a commonly used anticancer drug, is implicated in side effects such as neurotoxicity, nephrotoxicity and reduced blood cell count. Silver nanoparticles (AgNPs) have been investigated for their antibacterial effects and their anticancer activities to a lesser extent. Their capability as drug delivery vehicles has not been fully exploited, primarily due to their inconclusive cytotoxicity observed in healthy tissues. This study aimed to synthesize and characterize nanoparticles (NPs), consisting of Ag, chitosan (Cs) and folic acid (FA) (CsAg and FACsAg), loading them with cisplatin (C) (C-CsAg and C-FACsAg) and comparing their anticancer activities in the human embryonic kidney (HEK293), breast adenocarcinoma (MCF-7) and cervical carcinoma (HeLa) cells. All NPs and drug nanocomplexes were morphologically and physicochemically characterized, revealing NPs and nanocomplexes of favorable sizes ([Formula: see text][Formula: see text]nm), polydispersity and stability. The drug encapsulation efficiencies for C-CsAg and C-FACsAg were 50% and 72%, respectively, while drug release studies indicated that cisplatin release was pH dependent. The C-FACsAg nanocomplexes produced greater anticancer activity than C-CsAg. Folate receptor-mediated uptake was confirmed for the C-FACsAg nanocomplexes in the receptor-rich HeLa cells boding well for future in vivo research.

scholarly journals Biogenic Silver Nanoparticles Synthesized Using Mexican Poppy Plant Inhibits Cell Growth in Cancer Cells through Activation of Intrinsic Apoptosis Pathway

2020 ◽  
Vol 12 (3) ◽  
Author(s):  
Kailas Dhondibhau Datkhile ◽  
Satish Ramchandra Patil ◽  
Pratik Prakash Durgawale ◽  
Madhavi Narayan Patil ◽  
Nilam Jagannath Jagdale ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Cell Growth ◽  
Cancer Cells ◽  
Intrinsic Apoptosis ◽  
Apoptosis Pathway ◽  
Biogenic Silver Nanoparticles ◽  
Intrinsic Apoptosis Pathway

scholarly journals Analysis of BNIP3 and BNIP3L/Nix expression in cybrid cell lines harboring two LHON-associated mutations.

2019 ◽  
Author(s):  
Agata Kodroń ◽  
Parvana Hajieva ◽  
Agata Kulicka ◽  
Bohdan Paterczyk ◽  
Elona Jankauskaite ◽  
...  
Keyword(s):  
Cell Death ◽  
Optic Nerve ◽  
Cellular Response ◽  
Nerve Degeneration ◽  
Apoptosis Pathway ◽  
Mtdna Mutations ◽  
Cell Death Pathways ◽  
Intrinsic Apoptosis Pathway ◽  
Response To Stress ◽  
In Cells

Mitochondria are key players in cell death through the activation of the intrinsic apoptosis pathway. BNIP3 and BNIP3L/Nix are outer mitochondrial membrane bifunctional proteins which because of containing both BH3 and LIR domains play a role in cellular response to stress by regulation of apoptosis and selective autophagy. Leber’s Hereditary Optic Neuropathy (LHON) is the most common mitochondrial disease in adults, characterized by painless loss of vision caused by atrophy of the optic nerve. The disease in over 90% of cases is caused by one of three mutations in the mitochondrial genome: 11778G>A, 3460G>A or 14484T>C. The pathogenic processes leading to optic nerve degeneration are largely unknown, however, the most common explanation is that mtDNA mutations increase the apoptosis level in this tissue. Here we present the results of analysis of BNIP3 and BNIP3L/Nix proteins in cells harboring a combination of the 11778G>A and the 3460G>A LHON mutations. Experiments performed on cybrids revealed that BNIP3 protein level is decreased in LHON cells compared to controls. CCCP treatment resulted in apoptosis induction only in control cells. Moreover, we also noticed reduced level of autophagy in LHON cybrids. The presented results suggest that in cells carrying LHON mutations expression of proteins involved in regulation of apoptosis and autophagy is decreased what in turn may disturb cell death pathways in those cells and affect cellular response to stress.  

scholarly journals Biofabricated Fatty Acids-Capped Silver Nanoparticles as Potential Antibacterial, Antifungal, Antibiofilm and Anticancer Agents

2021 ◽  
Vol 14 (2) ◽  
pp. 139
Author(s):  
Mohammad Azam Ansari ◽  
Sarah Mousa Maadi Asiri ◽  
Mohammad A. Alzohairy ◽  
Mohammad N. Alomary ◽  
Ahmad Almatroudi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Silver Nanoparticles ◽  
Anticancer Agents ◽  
Sem Analysis ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Anticancer Efficacy ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Dose Dependent

The current study demonstrates the synthesis of fatty acids (FAs) capped silver nanoparticles (AgNPs) using aqueous poly-herbal drug Liv52 extract (PLE) as a reducing, dispersing and stabilizing agent. The NPs were characterized by various techniques and used to investigate their potent antibacterial, antibiofilm, antifungal and anticancer activities. GC-MS analysis of PLE shows a total of 37 peaks for a variety of bio-actives compounds. Amongst them, n-hexadecanoic acid (21.95%), linoleic acid (20.45%), oleic acid (18.01%) and stearic acid (13.99%) were found predominately and most likely acted as reducing, stabilizing and encapsulation FAs in LIV-AgNPs formation. FTIR analysis of LIV-AgNPs shows some other functional bio-actives like proteins, sugars and alkenes in the soft PLE corona. The zone of inhibition was 10.0 ± 2.2–18.5 ± 1.0 mm, 10.5 ± 2.5–22.5 ± 1.5 mm and 13.7 ± 1.0–16.5 ± 1.2 against P. aeruginosa, S. aureus and C. albicans, respectively. LIV-AgNPs inhibit biofilm formation in a dose-dependent manner i.e., 54.4 ± 3.1%—10.12 ± 2.3% (S. aureus), 72.7 ± 2.2%–23.3 ± 5.2% (P. aeruginosa) and 85.4 ± 3.3%–25.6 ± 2.2% (C. albicans), and SEM analysis of treated planktonic cells and their biofilm biomass validated the fitness of LIV-AgNPs in future nanoantibiotics. In addition, as prepared FAs rich PLE capped AgNPs have also exhibited significant (p < 0.05 *) antiproliferative activity against cultured HCT-116 cells. Overall, this is a very first demonstration on employment of FAs rich PLE for the synthesis of highly dispersible, stable and uniform sized AgNPs and their antibacterial, antifungal, antibiofilm and anticancer efficacy.

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