scholarly journals Grapefruit-Derived Micro and Nanovesicles Show Distinct Metabolome Profiles and Anticancer Activities in the A375 Human Melanoma Cell Line

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2722
Author(s):  
Christopher Stanly ◽  
Mariaevelina Alfieri ◽  
Alfredo Ambrosone ◽  
Antonietta Leone ◽  
Immacolata Fiume ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Fruit Juice ◽  
Substantial Effect ◽  
Cellular Level ◽  
Gas Chromatography Mass Spectrometry ◽  
Anticancer Activities ◽  
Alpha Hydroxy Acids ◽  
Sugar Derivatives ◽  
Cell Adhesion Molecule 1

Fruit juice is one of the most easily accessible resources for the isolation of plant-derived vesicles. Here we found that micro- and nano-sized vesicles (MVs and NVs) from four Citrus species, C. sinensis, C. limon, C. paradisi and C. aurantium, specifically inhibit the proliferation of lung, skin and breast cancer cells, with no substantial effect on the growth of non-cancer cells. Cellular and molecular analyses demonstrate that grapefruit-derived vesicles cause cell cycle arrest at G2/M checkpoint associated with a reduced cyclins B1 and B2 expression levels and the upregulation of cell cycle inhibitor p21. Further data suggest the inhibition of Akt and ERK signalling, reduced intercellular cell adhesion molecule-1 and cathepsins expressions, and the presence of cleaved PARP-1, all associated with the observed changes at the cellular level. Gas chromatography-mass spectrometry-based metabolomics reveals distinct metabolite profiles for the juice and vesicle fractions. NVs exhibit a high relative amount of amino acids and organic acids whereas MVs and fruit juice are characterized by a high percentage of sugars and sugar derivatives. Grapefruit-derived NVs are in particular rich in alpha–hydroxy acids and leucine/isoleucine, myo-inositol and doconexent, while quininic acid was detected in MVs. Our findings reveal the metabolite signatures of grapefruit-derived vesicles and substantiate their potential use in new anticancer strategies.

scholarly journals GC-MS profiling and assessment of antioxidant, antibacterial, and anticancer properties of extracts of Annona squamosa L. leaves

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Rawan Al-Nemari ◽  
Abdulrahman Al-Senaidy ◽  
Abdelhabib Semlali ◽  
Mohammad Ismael ◽  
Ahmed Yacine Badjah-Hadj-Ahmed ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Bioactive Compounds ◽  
Wound Repair ◽  
Gas Chromatography Mass Spectrometry ◽  
Nuclear Staining ◽  
Colon Cancer Cells ◽  
Annona Squamosa ◽  
Anticancer Activities ◽  
Alternative Source

Abstract Background The research and application of plants in food supplements and drugs have attracted great interest. This study aimed to examine the efficiency of several solvents for the extraction of the main compounds from Annona squamosa leaves and to evaluate the antioxidant, antibacterial, and anticancer activities of these extracts. Methods Gas chromatography-mass spectrometry was used to screen the bioactive compounds of A. squamosa methanolic extract. The free radical, hydrogen peroxide, and nitric oxide scavenging activities of the extracts were investigated. Furthermore, MTT, nuclear staining, LDH, and monolayer wound repair assays were performed to evaluate the potential anticancer activity of the extracts in colon cancer cells while the antibacterial activity was tested by using a well diffusion assay. Results A. squamosa leaves extracts were found to contain several bioactive compounds, of which the majority were sesquiterpenes (C15H24). These extracts exhibited strong antioxidant activity and antibacterial potency against both gram-positive and gram-negative bacteria. Different A. squamosa leaves extracts displayed remarkable antiproliferative, cytotoxic, antimigration, and apoptotic activities in colon cancer cells. Conclusions A. squamosa leaves contain major bioactive compounds that inhibit the growth of several types of bacteria and colon cancer cell lines, which demonstrated their efficacy as an alternative source of antibiotics and for the development of novel drugs for colon cancer therapy.

scholarly journals Shikonin Directly Targets Mitochondria and Causes Mitochondrial Dysfunction in Cancer Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Benjamin Wiench ◽  
Tolga Eichhorn ◽  
Malte Paulsen ◽  
Thomas Efferth
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Lines ◽  
Inflammatory Diseases ◽  
Multidrug Resistant ◽  
Resistant Cell ◽  
Live Cells ◽  
Anticancer Activities ◽  
Cycle Arrest ◽  
Therapy Success

Chemotherapy is a mainstay of cancer treatment. Due to increased drug resistance and the severe side effects of currently used therapeutics, new candidate compounds are required for improvement of therapy success. Shikonin, a natural naphthoquinone, was used in traditional Chinese medicine for the treatment of different inflammatory diseases and recent studies revealed the anticancer activities of shikonin. We found that shikonin has strong cytotoxic effects on 15 cancer cell lines, including multidrug-resistant cell lines. Transcriptome-wide mRNA expression studies showed that shikonin induced genetic pathways regulating cell cycle, mitochondrial function, levels of reactive oxygen species, and cytoskeletal formation. Taking advantage of the inherent fluorescence of shikonin, we analyzed its uptake and distribution in live cells with high spatial and temporal resolution using flow cytometry and confocal microscopy. Shikonin was specifically accumulated in the mitochondria, and this accumulation was associated with a shikonin-dependent deregulation of cellular Ca2+and ROS levels. This deregulation led to a breakdown of the mitochondrial membrane potential, dysfunction of microtubules, cell-cycle arrest, and ultimately induction of apoptosis. Seeing as both the metabolism and the structure of mitochondria show marked differences between cancer cells and normal cells, shikonin is a promising candidate for the next generation of chemotherapy.

scholarly journals Role of cell cycle progression on analyzing telomerase in cancer cells based on aggregation-induced emission luminogens

2021 ◽  
Author(s):  
Xia Wu ◽  
Jun Wu ◽  
Jun Dai ◽  
Biao Chen ◽  
Zhe Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Cellular Level ◽  
Fluorescence Signal ◽  
Cycle Progression ◽  
Tissue Samples ◽  
Normal Tissues ◽  
Tumor Identification ◽  
Cycle Dependent

ABSTRACT Telomerase acts as an important biomarker for tumor identification, which synthesizes telomeric repeats at the end of chromosomes telomeres during the replicative phase of cell cycle thus the expression level of telomerase changes as cell cycle progression. Although many efforts have been achieved in detecting the activity of TERT mRNA and active telomerase, the heterogeneous behavior of cell cycle was overlooked, which might affect the accuracy of their detection results. Herein, the AIEgen-based biosensing systems of PyTPA-DNA and Silole-R were developed to detect the cellular level of TERT mRNA and telomerase in different cell cycles. As a result, the fluorescence signal of cancer cells gradually increased from G0/G1, G1/S to S phase. In contrast, both cancer cells arrested at G2/M phase and normal cells exhibited the negligible fluorescence intensities. Comparing with normal tissues, malignant tumor samples demonstrated a significant turn-on fluorescence signal. Furthermore, the transcriptomics profiling revealed that tumor biomarkers changed as cell cycle progression and biomarkers of CA9, TK1 and EGFR were more abundantly expressed at early S stage. In this vein, our study represented the advanced biosensing tools for more accurate analyzing of cell cycle-dependent activity of TERT mRNA and active telomerase in clinical tissue samples.

Aloe-Emodin Enhances Tamoxifen Cytotoxicity by Suppressing Ras/ERK and PI3K/mTOR in Breast Cancer Cells

2017 ◽  
Vol 45 (02) ◽  
pp. 337-350 ◽  
Author(s):  
Hsin-Shun Tseng ◽  
Yu-Fen Wang ◽  
Yew-Min Tzeng ◽  
Dar-Ren Chen ◽  
Ya-Fan Liao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Aloe Vera ◽  
Breast Cancer Cell Lines ◽  
Anticancer Activities ◽  
Anticancer Efficacy ◽  
Aloe Emodin ◽  
Mcf 7

Aloe-emodin (AE) is derived from Aloe vera and rhubarb (Rheum palmatum) and exhibits anticancer activities via multiple regulatory mechanisms in various cancers. AE can also enhance the anticancer efficacy of cisplatin, doxorubicin, docetaxel, and 5-fluorouracil; however, its effects remain poorly characterized. MCF-7, MDA-MB-231, MDA-MB-468, BT-474, and HCC-1954 breast cancer cell lines were treated with the indicated conditions of AE, and cell viability assays were performed. The expression levels of signaling proteins were determined by western blot analysis, intracellular reactive oxygen species (ROS), cell cycle distributions, and rates of apoptosis as estimated by flow cytometry. In comparison with other cells, MCF-7 cells were more sensitive to AE treatment; AE enhanced the cytotoxicity of 9[Formula: see text][Formula: see text]g/ml tamoxifen by reducing EGFR, ER[Formula: see text], Ras, ERK, c-Myc, and mTOR protein expression and blocking PI3K and mTOR activation. Finally, although co-treatment of AE with tamoxifen increased intracellular ROS, there were no effects on cell cycle progression. Besides facilitating tamoxifen-induced cell death, AE also enhanced the antiproliferative activity of tamoxifen by blocking Ras/ERK and PI3K/mTOR pathways in breast cancer cells, thus demonstrating the chemosensitizing potential of AE.

scholarly journals A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities

2016 ◽  
Vol 39 (3) ◽  
pp. 871-888 ◽  
Author(s):  
Youlin Deng ◽  
Zhongliang Wang ◽  
Fugui Zhang ◽  
Min Qiao ◽  
Zhengjian Yan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Anticancer Activities ◽  
Cycle Progression ◽  
Igf Signaling

Background/Aims: Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells. Methods: Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus-mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are assessed using pathway-specific reporters. Subcutaneous xenograft model is used to determine anticancer activity. Results: We find that Niclosamide is highly effective on inhibiting cell proliferation, cell migration, and cell cycle progression, and inducing apoptosis in human ovarian cancer cells, possibly by targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and NFkB. Silencing IGF-1R exert a similar but weaker effect than that of Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer cells to Niclosamide-induced anti-proliferative and anticancer activities both in vitro and in vivo. Conclusion: Niclosamide as a repurposed anticancer agent may be more efficacious when combined with agents that target other signaling pathways such as IGF signaling in the treatment of human cancers including ovarian cancer.

Lupeol Inhibits Proliferation and Promotes Apoptosis of Ovarian Cancer Cells by Inactivating Phosphoinositide-3-Kinase/Protein Kinase B/ Mammalian Target of Rapamycin Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 206-210
Author(s):  
Feng Chen ◽  
Bei Zhang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Protein Kinase ◽  
Cell Viability ◽  
Cancer Cells ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Ovarian Cancer Cells ◽  
Phosphoinositide 3 Kinase

Lupeol exhibits multiple pharmacological activities including, anticancerous, anti-inflammatory, and antioxidant. The aim of this study was to explore the anticancerous activity of lupeol on ovarian cancer cells and examine its mechanism of action. To this end, increasing concentrations of lupeol on cell viability, cell cycle, and apoptosis in Caov-3 cells were evaluated. Lupeol inhibited cell viability, induced G1 phase arrest in cell cycle, increased cell apoptosis, and inhibited the ratio of phospho-Akt/protein kinase B and phospho-mammalian target of rapamycin/mammalian target of rapamycin. In conclusion, these data suggest that lupeol may play a therapeutic role in ovarian cancer.

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