scholarly journals Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 191
Author(s):  
Ambre Dezaire ◽  
Christophe H. Marchand ◽  
Marine Vallet ◽  
Nathalie Ferrand ◽  
Soraya Chaouch ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Crude Extract ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
Cancer Cell Line ◽  
Anticancer Activities ◽  
Chemical Library ◽  
Altered Expression ◽  
Cancer Aggressiveness

High-throughput screening assays have been designed to identify compounds capable of inhibiting phenotypes involved in cancer aggressiveness. However, most studies used commercially available chemical libraries. This prompted us to explore natural products isolated from marine-derived fungi as a new source of molecules. In this study, we established a chemical library from 99 strains corresponding to 45 molecular operational taxonomic units and evaluated their anticancer activity against the MCF7 epithelial cancer cell line and its invasive stem cell-like MCF7-Sh-WISP2 counterpart. We identified the marine fungal Paradendryphiella salina PC 362H strain, isolated from the brown alga Pelvetia caniculata (PC), as one of the most promising fungi which produce active compounds. Further chemical and biological characterizations of the culture of the Paradendryphiella salina PC 362H strain identified (-)-hyalodendrin as the active secondary metabolite responsible for the cytotoxic activity of the crude extract. The antitumor activity of (-)-hyalodendrin was not only limited to the MCF7 cell lines, but also prominent on cancer cells with invasive phenotypes including colorectal cancer cells resistant to chemotherapy. Further investigations showed that treatment of MCF7-Sh-WISP2 cells with (-)-hyalodendrin induced changes in the phosphorylation status of p53 and altered expression of HSP60, HSP70 and PRAS40 proteins. Altogether, our study reveals that this uninvestigated marine fungal crude extract possesses a strong therapeutic potential against tumor cells with aggressive phenotypes and confirms that members of the epidithiodioxopiperazines are interesting fungal toxins with anticancer activities.

Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths

2019 ◽  
Vol 15 (5) ◽  
pp. 550-560
Author(s):  
Mateusz D. Tomczyk ◽  
Anna Byczek-Wyrostek ◽  
Klaudia Strama ◽  
Martyna Wawszków ◽  
Przemysław Kasprzycki ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Topoisomerase Ii ◽  
Significant Activity ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
Substitution Pattern ◽  
Topo Ii

Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Methods: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

scholarly journals Phytochemical screening and anticancer activity of the aerial parts extract of Xanthium strumarium L. on HepG2 cancer cell line

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hai Trieu Ly ◽  
Trieu Minh Truong ◽  
Thi Thu Huong Nguyen ◽  
Hoang Dung Nguyen ◽  
Yuxia Zhao ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Proliferative Activity ◽  
Herbal Medicines ◽  
Cancer Cell Line ◽  
Cancer Therapeutics ◽  
Ethanol Extract ◽  
Xanthium Strumarium ◽  
Aerial Parts ◽  
Dual Staining

Abstract Background Cancer is one of the most considerable concerns because of increasing the death rate all over the world. Recent studies have disclosed that plant extracts exhibit anticancer activity through various mechanisms. Xanthium strumarium has been used by Vietnamese in herbal medicines to support the medication of infirmities. This study is to consider the secondary metabolites, antioxidant and anticancer capacities of extract from the aerial parts (stems and leaves) of X. strumarium (AP-XS). Methods AP-XS was analyzed for the presence of phytochemicals via qualitative chemical tests and determined total polyphenol and flavonoid contents. DPPH (1,1-diphenyl-2-picrylhydrazyl) quenching assay and sulforhodamine B (SRB) assay were selected to investigate antioxidant capacity and anti-proliferative activity, respectively. Besides, acridine orange-ethidium bromide (AO-EB) dual staining was applied to evaluate the ability to induce apoptosis on HepG2 cancer cells. Results Results of present study indicated that AP-XS contains the main phytochemicals such as flavonoids, tannins, saponins, alkaloids, and triterpenes. Ethanol extract had highest content of polyphenol (84.86 mg gallic acid equivalent/g dry mass), and exhibited the great total antioxidant property (IC50 = 184.13 μg/mL) and anti-proliferative activity on HepG2 cancer cells (IC50 = 81.69 μg/mL). Furthermore, the characteristics of apoptosis including shrinkage of the cell and apoptotic bodies were found following 60 h of AP-XS extract treatment through AO-EB dual staining. Conclusion The data suggest that AP-XS extract had antioxidant potential and anti-proliferative effect. The anti-proliferative property was considered to have an association with a rising of apoptosis. These results were reliable for further research on X. strumarium as a source of phytochemicals with anticancer activity potential for cancer therapeutics.

scholarly journals New Inhibitory Effects of Cilnidipine on Microglial P2X7 Receptors and IL-1β Release: An Involvement in its Alleviating Effect on Neuropathic Pain

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 434
Author(s):  
Tomohiro Yamashita ◽  
Sawako Kamikaseda ◽  
Aya Tanaka ◽  
Hidetoshi Tozaki-Saitoh ◽  
Jose M. M. Caaveiro ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
High Throughput Screening ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Inhibitory Effect ◽  
Intrathecal Administration ◽  
Chemical Library ◽  
P2x7 Receptors ◽  
Approved Drugs ◽  
Cardinal Symptom

P2X7 receptors (P2X7Rs) belong to a family of ATP-gated non-selective cation channels. Microglia represent a major cell type expressing P2X7Rs. The activation of microglial P2X7Rs causes the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β). This response has been implicated in neuroinflammatory states in the central nervous system and in various diseases, including neuropathic pain. Thus, P2X7R may represent a potential therapeutic target. In the present study, we screened a chemical library of clinically approved drugs (1979 compounds) by high-throughput screening and showed that the Ca2+ channel blocker cilnidipine has an inhibitory effect on rodent and human P2X7R. In primary cultured rat microglial cells, cilnidipine inhibited P2X7R-mediated Ca2+ responses and IL-1β release. Moreover, in a rat model of neuropathic pain, the intrathecal administration of cilnidipine produced a reversal of nerve injury-induced mechanical hypersensitivity, a cardinal symptom of neuropathic pain. These results point to a new inhibitory effect of cilnidipine on microglial P2X7R-mediated inflammatory responses and neuropathic pain, proposing its therapeutic potential.

scholarly journals NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Wei-Jan Huang ◽  
Yu-Chih Liang ◽  
Shuang-En Chuang ◽  
Li-Ling Chi ◽  
Chi-Yun Lee ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Xenograft Model ◽  
Cyclin B1 ◽  
Dependent Manner ◽  
Cell Cycle Regulators ◽  
Anticancer Activities ◽  
Gene Expressions

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1,p21(Waf1/Cip1)gene expression had markedly increased whilecyclin B1andD1gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor genep53in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activityin vitroandin vivo.

scholarly journals Synthesis, Antibacterial and Anticancer Activities Evaluation of New 4-Thiazolidinone-Indolin-2-One Analogs

2021 ◽  
Vol 12 (6) ◽  
pp. 8094-8104
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
A549 Cells ◽  
Cancer Cell Line ◽  
Mitochondrial Pathway ◽  
Knoevenagel Reaction ◽  
Anticancer Activities ◽  
Dapi Staining ◽  
Mcf 7

A series of novel thiazolidinone-isatin hybrids have been synthesized through the Knoevenagel reaction of isatin derivatives with synthesized thiazolidinone scaffolds and then evaluated for their in vitro antibacterial effects on Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus). Cytotoxic effects of the compounds on non-small-cell lung cancer cells (A549 cells), breast epithelial cancer cell line (MCF-7), and prostate cancer cells (PC3 cells) were investigated. Among compounds tested for antibacterial activity, S. aureus was susceptible to compound 7d. The most potent compounds against A549, MCF-7, and PC3 tumor cells were found to be 7g. DAPI staining of all cancer cell lines treated with compound 7g, associated with cell death. We finally confirmed that apoptosis occurred in A549 cells by up-regulated Bax expression and down-regulated Bcl-2 expression from the mitochondrial pathway of apoptosis by using the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) method. Our findings suggested that compound 7g may be a good target in designing cancer therapy strategies.

scholarly journals A Phenylfurocoumarin Derivative Reverses ABCG2-Mediated Multidrug Resistance In Vitro and In Vivo

2021 ◽  
Vol 22 (22) ◽  
pp. 12502
Author(s):  
Shoji Kokubo ◽  
Shinobu Ohnuma ◽  
Megumi Murakami ◽  
Haruhisa Kikuchi ◽  
Shota Funayama ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
High Throughput Screening ◽  
Atp Hydrolysis ◽  
Pheophorbide A ◽  
Chemical Library ◽  
Hct 116 ◽  
Potential Inhibitors

The ATP-binding cassette subfamily G member 2 (ABCG2) transporter is involved in the development of multidrug resistance in cancer patients. Many inhibitors of ABCG2 have been reported to enhance the chemosensitivity of cancer cells. However, none of these inhibitors are being used clinically. The aim of this study was to identify novel ABCG2 inhibitors by high-throughput screening of a chemical library. Among the 5812 compounds in the library, 23 compounds were selected in the first screening, using a fluorescent plate reader-based pheophorbide a (PhA) efflux assay. Thereafter, to validate these compounds, a flow cytometry-based PhA efflux assay was performed and 16 compounds were identified as potential inhibitors. A cytotoxic assay was then performed to assess the effect these 16 compounds had on ABCG2-mediated chemosensitivity. We found that the phenylfurocoumarin derivative (R)-9-(3,4-dimethoxyphenyl)-4-((3,3-dimethyloxiran-2-yl)methoxy)-7H-furo [3,2-g]chromen-7-one (PFC) significantly decreased the IC50 of SN-38 in HCT-116/BCRP colon cancer cells. In addition, PFC stimulated ABCG2-mediated ATP hydrolysis, suggesting that this compound interacts with the substrate-binding site of ABCG2. Furthermore, PFC reversed the resistance to irinotecan without causing toxicity in the ABCG2-overexpressing HCT-116/BCRP cell xenograft mouse model. In conclusion, PFC is a novel inhibitor of ABCG2 and has promise as a therapeutic to overcome ABCG2-mediated MDR, to improve the efficiency of cancer chemotherapy.

Anticancer Activity and High Content Screening of New 6-Substituted-5,6-dihydrobenzo[4,5]imidazo[1,2-c]quinazoline Derivatives

2021 ◽  
pp. 2397-2405
Author(s):  
Hiba Ali Hasan ◽  
Afrah Salman ◽  
Abdulmalek Emilia
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Elemental Analysis ◽  
Inhibitory Concentration ◽  
High Content Screening ◽  
Spectroscopic Methods ◽  
High Toxicity ◽  
Anticancer Activities ◽  
Microwave Assisted ◽  
Quinazoline Derivatives

Pursuing our interest in bioactive heterocyclic compound, two benzoimidazoquinazoline derivatives were synthesised using both microwave-assisted and classical heating methods. Structures of the compounds were confirmed by standard spectroscopic methods and elemental analysis. The target scaffolds were incidentally found to emit blue light when exposed to ultraviolet light. Consequently, a photoluminescence characterization was carried out as a part of characterization protocol. The anticancer activities of the benzimidazoquinazoline compounds were investigated using both methylthiazol tetrazolium (MTT) and the high content screen (HCS) assays against liver hepatocellular cells. The results showed a significant reduction in the inhibitory concentration of the cancer cells by 1 and 2.6 fold when exposed to compounds (3a) and (3b), respectively. The high content screen (HCS) was conducted for compound (3b) and the results showed high toxicity towards the cancer cells.

scholarly journals MDA-MB-231 Breast Cancer Cells Resistant to Pleurocidin-Family Lytic Peptides Are Chemosensitive and Exhibit Reduced Tumor-Forming Capacity

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1220
Author(s):  
Ashley L. Hilchie ◽  
Erin E. Gill ◽  
Melanie R. Power Coombs ◽  
Reza Falsafi ◽  
Robert E. W. Hancock ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Anticancer Agents ◽  
Therapeutic Potential ◽  
Cancer Cell Line ◽  
Matrix Composition ◽  
Breast Cancer Cell Lines ◽  
Lytic Peptides

Direct-acting anticancer (DAA) peptides are cytolytic peptides that show promise as novel anticancer agents. DAA peptides bind to anionic molecules that are abundant on cancer cells relative to normal healthy cells, which results in preferential killing of cancer cells. Due to the mechanism by which DAA peptides kill cancer cells, it was thought that resistance would be difficult to achieve. Here, we describe the generation and characterization of two MDA-MB-231 breast cancer cell-line variants with reduced susceptibility to pleurocidin-family and mastoparan DAA peptides. Peptide resistance correlated with deficiencies in peptide binding to cell-surface structures, suggesting that resistance was due to altered composition of the cell membrane. Peptide-resistant MDA-MB-231 cells were phenotypically distinct yet remained susceptible to chemotherapy. Surprisingly, neither of the peptide-resistant breast cancer cell lines was able to establish tumors in immune-deficient mice. Histological analysis and RNA sequencing suggested that tumorigenicity was impacted by alternations in angiogenesis and extracellular matrix composition in the peptide-resistant MDA-MB-231 variants. Collectively, these data further support the therapeutic potential of DAA peptides as adjunctive treatments for cancer.

scholarly journals Evaluation and comparison of anti-cancer activity of dapagliflozin and canagliflozin in oral cancer cell line: an in vitro study

2019 ◽  
Vol 8 (3) ◽  
pp. 473 ◽  
Author(s):  
Nenavath Vinay ◽  
Darling Chellathai David
Keyword(s):  
Oral Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Sglt2 Inhibitors ◽  
Cytotoxic Assay ◽  
Oral Cancer Cell ◽  
Oral Cancer Cell Line

Background: Cancer is rapidly evolving life-threatening ailment in the mankind due to changes in daily food intake and lifestyle changes. Oral carcinoma is 6th major cause of cancer death in the world and it is third major reason of cancer mortality in India. Every cell in the human body requires glucose for its metabolic energy. Besides normal cell, cancer cells also require the glucose for its endurance and multiplication. SGLT2 inhibitors which are aimed at diabetes therapy exhibited anticancer properties also in colon and pancreatic cancer lines. Present study aim is to evaluate the anticancer activity of SGLT2 inhibitors against oral cancer cell by MTT Assay.Methods: To evaluate the anticancer activity of SGLT2 inhibitors MTT Cytotoxic assay is performed as per standard protocols. Cancer cells were plated in 24-well plates and incubated at 370C with 5% CO2 condition. After convergence, samples are added to the plates in various concentrations and allowed to incubate then they are detached from the plates and cleansed with the reagents. The wells are coated with the dye and incubated. Later samples are analysed in UV-spectrophotometer.Results: Cytotoxic assay showed decrease in cell viability with increasing dose of SGLT2 inhibitors. IC50 values were determined graphically. The IC50 value of dapagliflozin is 400µg/ml and canagliflozin is 250µg/ml respectively after 24 hours of Assessment.Conclusions: The results of the current study give us an evidence that SGLT2 inhibitors dapagliflozin and canagliflozin exhibits anticancer property in Oral Cancer cell line.

scholarly journals Corilagin in Cancer: A Critical Evaluation of Anticancer Activities and Molecular Mechanisms

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3399 ◽  
Author(s):  
Ashutosh Gupta ◽  
Amit Kumar Singh ◽  
Ramesh Kumar ◽  
Risha Ganguly ◽  
Harvesh Kumar Rana ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Critical Evaluation ◽  
Cancer Cell Line ◽  
Anticancer Activities ◽  
Altered Expression ◽  
Anticancer Efficacy ◽  
Extracellular Signal ◽  
M Phase ◽  
Induced Apoptosis

Corilagin (β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), an ellagitannin, is one of the major bioactive compounds present in various plants. Ellagitannins belong to the hydrolyzable tannins, a group of polyphenols. Corilagin shows broad-spectrum biological, and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, and antitumor actions. Natural compounds possessing antitumor activities have attracted significant attention for treatment of cancer. Corilagin has shown inhibitory activity against the growth of numerous cancer cells by prompting cell cycle arrest at the G2/M phase and augmented apoptosis. Corilagin-induced apoptosis and autophagic cell death depends on production of intracellular reactive oxygen species in breast cancer cell line. It blocks the activation of both the canonical Smad and non-canonical extracellular-signal-regulated kinase/Akt (protein kinase B) pathways. The potential apoptotic action of corilagin is mediated by altered expression of procaspase-3, procaspase-8, procaspase-9, poly (ADP ribose) polymerase, and Bcl-2 Bax. In nude mice, corilagin suppressed cholangiocarcinoma growth and downregulated the expression of Notch1 and mammalian target of rapamycin. The aim of this review is to summarize the anticancer efficacy of corilagin with an emphasis on the molecular mechanisms involving various signaling pathways in tumor cells.

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