scholarly journals The Effect of Compound Kushen Injection on Cancer Cells: Integrated Identification of Candidate Molecular Mechanisms

2018 ◽  
Author(s):  
Jian Cui ◽  
Zhipeng Qu ◽  
Yuka Harata-Lee ◽  
Hanyuan Shen ◽  
Thazin Nwe Aung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Candidate Genes ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Complex Mixtures ◽  
Systematic Analysis ◽  
Molecular Changes ◽  
Compound Kushen Injection

AbstractBackgroundBecause Traditional Chinese Medicine (TCM) preparations are often combinations of multiple herbs containing hundreds of compounds, they have been difficult to study. Compound Kushen Injection (CKI) is a complex mixture cancer treatment used in Chinese hospitals for over twenty years.PurposeTo demonstrate that a systematic analysis of molecular changes resulting from complex mixtures of bioactives from TCM can identify a core set of differentially expressed (DE) genes and a reproducible set of candidate pathways.Study DesignWe used a cancer cell culture model to measure the effect of CKI on cell cycle phases, apoptosis and correlate those phenotypes with CKI induced changes in gene expression.MethodsWe treated cancer cells with CKI in order to generate and analyse high-throughput transcriptome data from two cancer cell lines. We integrated these differential gene expression results with previously reported results.ResultsCKI induced cell-cycle arrest and apoptosis and altered the expression of 363 core candidate genes associated with cell cycle, apoptosis, DNA replication/repair and various cancer pathways. Of these, 7 are clinically relevant to cancer diagnosis or therapy and 14 are cell cycle regulators, and most of these 21 candidates are downregulated by CKI. Comparison of our core candidate genes to a database of plant medicinal compounds and their effects on gene expression identified one-to-one, one-to-many and many-to-many regulatory relationships between compounds in CKI and DE genes.ConclusionsBy identifying promising candidate pathways and genes associated with CKI based on our transcriptome-based analysis, we have shown this approach is useful for the systematic analysis of molecular changes resulting from complex mixtures of bioactives.

Adenosine Analogues as Opposite Modulators of the Cisplatin Resistance of Ovarian Cancer Cells

2019 ◽  
Vol 19 (4) ◽  
pp. 473-486 ◽  
Author(s):  
Katarzyna Bednarska-Szczepaniak ◽  
Damian Krzyżanowski ◽  
Magdalena Klink ◽  
Marek Nowak
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Biology ◽  
Immune Cell ◽  
Immunosuppressive Agents ◽  
Cell Activity ◽  
Ovarian Cancer Cells ◽  
Adenosine Analogues

Background: Adenosine released by cancer cells in high amounts in the tumour microenvironment is one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive and cisplatin-resistant ovarian cancer cells to cisplatin treatment. Methods: The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/ antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis events and cisplatin incorporation in cancer cells were determined. Results: PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring mitochondrial and plasma membrane potentials that were disturbed by cisplatin. Conclusion: Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell biology should be considered in the context of supportive chemotherapy for ovarian cancer.

scholarly journals Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 795
Author(s):  
Lukas Gorecki ◽  
Martin Andrs ◽  
Jan Korabecny
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Current Status ◽  
Future Perspectives ◽  
Phase Ii Trials ◽  
Anticancer Treatment ◽  
Positive Outlook ◽  
Insight Into

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

scholarly journals Arsenic hexoxide has differential effects on cell proliferation and genome-wide gene expression in human primary mammary epithelial and MCF7 cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donguk Kim ◽  
Na Yeon Park ◽  
Keunsoo Kang ◽  
Stuart K. Calderwood ◽  
Dong-Hyung Cho ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammary Epithelial ◽  
Mcf7 Cells ◽  
Differential Effects ◽  
Cycle Arrest ◽  
Genome Wide ◽  
Human Mammary Epithelial ◽  
Genome Wide Gene Expression

AbstractArsenic is reportedly a biphasic inorganic compound for its toxicity and anticancer effects in humans. Recent studies have shown that certain arsenic compounds including arsenic hexoxide (AS4O6; hereafter, AS6) induce programmed cell death and cell cycle arrest in human cancer cells and murine cancer models. However, the mechanisms by which AS6 suppresses cancer cells are incompletely understood. In this study, we report the mechanisms of AS6 through transcriptome analyses. In particular, the cytotoxicity and global gene expression regulation by AS6 were compared in human normal and cancer breast epithelial cells. Using RNA-sequencing and bioinformatics analyses, differentially expressed genes in significantly affected biological pathways in these cell types were validated by real-time quantitative polymerase chain reaction and immunoblotting assays. Our data show markedly differential effects of AS6 on cytotoxicity and gene expression in human mammary epithelial normal cells (HUMEC) and Michigan Cancer Foundation 7 (MCF7), a human mammary epithelial cancer cell line. AS6 selectively arrests cell growth and induces cell death in MCF7 cells without affecting the growth of HUMEC in a dose-dependent manner. AS6 alters the transcription of a large number of genes in MCF7 cells, but much fewer genes in HUMEC. Importantly, we found that the cell proliferation, cell cycle, and DNA repair pathways are significantly suppressed whereas cellular stress response and apoptotic pathways increase in AS6-treated MCF7 cells. Together, we provide the first evidence of differential effects of AS6 on normal and cancerous breast epithelial cells, suggesting that AS6 at moderate concentrations induces cell cycle arrest and apoptosis through modulating genome-wide gene expression, leading to compromised DNA repair and increased genome instability selectively in human breast cancer cells.

scholarly journals The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huilin Zhang ◽  
Ping He ◽  
Qing Zhou ◽  
Yan Lu ◽  
Bingjian Lu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cervical Cancers ◽  
Cervical Cancer Cells

Abstract Background CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet. Methods Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression. Results We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells. Conclusions Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

scholarly journals Overexpression of β-Arrestins inhibits proliferation and motility in triple negative breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saber Yari Bostanabad ◽  
Senem Noyan ◽  
Bala Gur Dedeoglu ◽  
Hakan Gurdal
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Function ◽  
Expression Profiles ◽  
Tissue Samples ◽  
Expression Levels ◽  
Cell Cycle Genes

Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.

The Potential Oncogenic and MLN4924-Resistant Effects of CSN5 on Cervical Cancer Cells

2021 ◽  
Author(s):  
Huilin Zhang ◽  
Ping He ◽  
Qing Zhou ◽  
Yan Lu ◽  
Bingjian Lu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cervical Cancers ◽  
Cervical Cancer Cells

Abstract BackgroundsCSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet.MethodsData from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR-CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. CCK8, clone formation assay and cell cycle assay were also employed. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. Moreover, MLN4924 was applied in Siha and Hela with CSN5 overexpression.ResultsWe found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells.ConclusionsOur findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

scholarly journals Xanthohumol Induces Growth Inhibition and Apoptosis in Ca Ski Human Cervical Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Wai Kuan Yong ◽  
Sri Nurestri Abd Malek
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Morphological Changes ◽  
S Phase ◽  
Phase Cell ◽  
Cervical Cancer Cell Line ◽  
Dependent Manner ◽  
Cervical Cancer Cells

We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50values using sulforhodamine B (SRB) assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for cervical cancer.

scholarly journals Paclitaxel and trastuzumab treatment affects insulin growth factor I expression in breast cancer cell lines

2015 ◽  
Vol 10 (4) ◽  
pp. 799 ◽  
Author(s):  
Yu-Xian Qian ◽  
Rui Yu ◽  
Shi-Rong Qin
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Factor I ◽  
Trastuzumab Treatment ◽  
Cycle Arrest

<p class="Abstract">Breast cancer is the most common type of cancers and second primary cause of death among women. Insulin-like growth factor I (IGF-1) signaling pathway plays a vital role in cancer cell survival, proliferation, chemotaxis and angiogenesis. In this study, the effect of combination of two drugs, paclitaxel and trastuzumab on IGF signaling and cell cycle arrest in breast cancer cell lines, T47D and Hs0578T were explored. The interaction of paclitaxel and trastuzumab on IGF-1 signaling pathway was studied with IGF-1 and phosphoinositide 3-kinase inhibitor, LY294002. The protein expression of IGF signaling molecules were reduced in the drug treated cancer cells. LY294002 and IGF-1 with paclitaxel and trastuzumab treatment inhibited phosphorylated Akt. During G0/G1 phase, cell cycle arrest and accumulation of apoptotic cells were observed in drug treated cancer cells. The synergistic effect of paclitaxel and trastuzumab decreased the multiplication of breast cancer cells by altering the expression of IGF-I signaling molecules. This combination proves to be one of the useful methods to treat breast cancer.</p><p> </p>

scholarly journals Transcriptomic signatures of ageing vary in solitary and social forms of an orchid bee

2020 ◽  
Author(s):  
Alice C. Séguret ◽  
Eckart Stolle ◽  
Fernando A. Fleites-Ayil ◽  
José Javier G. Quezada-Euán ◽  
Klaus Hartfelder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Juvenile Hormone ◽  
Candidate Genes ◽  
Gene Networks ◽  
Life Histories ◽  
Molecular Mechanisms ◽  
Trade Off ◽  
Eusocial Insects ◽  
Orchid Bee ◽  
Social Forms

AbstractEusocial insect queens are remarkable in their ability to maximise both fecundity and longevity, thus escaping the typical trade-off between these two traits. In species exhibiting complex eusocial behaviour, several mechanisms have been proposed to underlie the remoulding of the trade-off, such as reshaping of the juvenile hormone pathway, or caste-specific susceptibility to oxidative stress. However, it remains a challenge to disentangle the molecular mechanisms underlying the remoulding of the trade-off in eusocial insects from caste-specific physiological attributes that have subsequently arisen due to their different life histories. Socially plastic species such as the orchid bee Euglossa viridissima represent excellent models to address the role of sociality per se in longevity as they allow direct comparisons of solitary and social individuals within a common genetic background. We present data on gene expression and juvenile hormone levels from young and old bees, from both solitary and social nests. We found 940 genes to be differentially expressed with age in solitary females, versus only 14 genes in social dominant females, and seven genes in subordinate females. We performed a weighted gene co-expression network analysis to further highlight candidate genes related to ageing in this species. Primary “ageing gene” candidates were related to protein synthesis, gene expression, immunity and venom production. Remarkably, juvenile hormone titres did not vary with age or social status. These results represent an important step in understanding the proximate mechanisms underlying the remodeling of the fecundity/longevity trade-off that accompanies the evolutionary transition from solitary life to eusociality.Significance statementThe remarkably long lifespan of the queens of eusocial insects despite their high reproductive output suggests that they are not subject to the widespread trade-off between fecundity and longevity that governs solitary animal life histories, yet surprisingly little is known of the molecular mechanisms underpinning their longevity. Using a socially plastic bee in which some individuals of a population are social whilst others are solitary, we identified hundreds of candidate genes and related gene networks that are involved in the remoulding of the fecundity/longevity tradeoff. As well as identifying candidate ageing genes, our data suggest that even in incipient stages of sociality there is a marked reprogramming of ageing; long live the queen.

scholarly journals The Potential Prognostic Role of Oligosaccharide-Binding Fold-Containing Protein 2A (OBFC2A) in Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Qianxue Wu ◽  
Xin Tang ◽  
Wenming Zhu ◽  
Qing Li ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Candidate Genes ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
G1 Phase ◽  
And Migration

BackgroundPatients with triple-negative breast cancer (TNBC) have poor overall survival. The present study aimed to investigate the potential prognostics of TNBC by analyzing breast cancer proteomic and transcriptomic datasets.MethodsCandidate proteins selected from CPTAC (the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium) were validated using datasets from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium). Kaplan-Meier analysis and ROC (receiver operating characteristic) curve analysis were performed to explore the prognosis of candidate genes. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were performed on the suspected candidate genes. Single-cell RNA-seq (scRNA-seq) data from GSE118389 were used to analyze the cell clusters in which OBFC2A (Oligosaccharide-Binding Fold-Containing Protein 2A) was mainly distributed. TIMER (Tumor Immune Estimation Resource) was used to verify the correlation between OBFC2A expression and immune infiltration. Clone formation assays and wound healing assays were used to detect the role of OBFC2A expression on the proliferation, invasion, and migration of breast cancer cells. Flow cytometry was used to analyze the effects of silencing OBFC2A on breast cancer cell cycle and apoptosis.ResultsSix candidate proteins were found to be differentially expressed in non-TNBC and TNBC groups from CPTAC. However, only OBFC2A was identified as an independently poor prognostic gene marker in METABRIC (HR=3.658, 1.881-7.114). And OBFC2A was associated with immune functions in breast cancer. Biological functional experiments showed that OBFC2A might promote the proliferation and migration of breast cancer cells. The inhibition of OBFC2A expression blocked the cell cycle in G1 phase and inhibited the transformation from G1 phase to S phase. Finally, downregulation of OBFC2A also increased the total apoptosis rate of cells.ConclusionOn this basis, OBFC2A may be a potential prognostic biomarker for TNBC.

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