scholarly journals P16 methylation increases the sensitivity of cancer cells to the CDK4/6 inhibitor palbociclib

2019 ◽  
Author(s):  
Paiyun Li ◽  
Xuehong Zhang ◽  
Liankun Gu ◽  
Jing Zhou ◽  
Dajun Deng
Keyword(s):  
Dna Methylation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Copy Number ◽  
Dna Methyltransferase ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Gene Copy

AbstractThe P16 (CDKN2Aink4a) gene is an endogenous CDK4/6 inhibitor. Palbociclib (PD0332991) is an anti-CDK4/6 chemical for cancer treatment. P16 is most frequently inactivated by copy number deletion and DNA methylation in cancers. It is well known that cancer cells with P16 deletion are more sensitive to palbociclib than those without. However, whether P16 methylation is related to palbociclib sensitivity is not known. By analyzing public pharmacogenomic datasets, we found that the IC50 of palbociclib in cancer cell lines (n=522) was positively correlated with both the P16 expression level and P16 gene copy number. Our experimental results further showed that cancer cell lines with P16 methylation were more sensitive to palbociclib than those without. To determine whether P16 methylation directly increased the sensitivity of cancer cells to palbociclib, we induced P16 methylation in the lung cancer cell lines H661 and HCC827 and the gastric cancer cell line BGC823 via an engineered P16-specific DNA methyltransferase (P16-Dnmt) and found that the sensitivity of these cells to palbociclib was significantly increased. The survival rate of P16-Dnmt cells was significantly lower than that of vector control cells 48 hrs post treatment with palbociclib (10 μM). Notably, palbociclib treatment also selectively inhibited the proliferation of the P16-methylated subpopulation of P16-Dnmt cells, further indicating that P16 methylation can increase the sensitivity of cells to this CDK4/6 inhibitor. These results were confirmed in an animal experiment. In conclusion, inactivation of the P16 gene by DNA methylation can increase the sensitivity of cancer cells to palbociclib.

scholarly journals 8-Hydroxycudraxanthone G Suppresses IL-8 Production in SP-C1 Tongue Cancer Cells

2014 ◽  
Vol 9 (1) ◽  
pp. 1934578X1400900
Author(s):  
Arlette S. Setiawan ◽  
Roosje R. Oewen ◽  
Supriatno ◽  
Willyanti Soewondo ◽  
Sidik ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Therapeutic Intervention ◽  
Tongue Cancer ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Garcinia Mangostana ◽  
Anti Cancer ◽  
Cancer Activity

Production of IL-8 primarily promotes angiogenic responses in cancer cells, which lead to favorable disease progression. Suppressing this production may, therefore, be a significant therapeutic intervention in targeting tumor angiogenesis. This study aimed to evaluate the reduction effects of xanthones in cancer cell lines. Nine known prenylated xanthones (1–9), isolated from the pericarp of Garcinia mangostana Linn (GML), were tested for their ability to suppress IL-8 (interleukin-8) of the SP-C1 (Supri's Clone 1) tongue cancer cell line. Of these compounds, 8-hydroxycudraxanthone-G (4) suppressed IL-8 within 48 hours. This is the first report of 8-hydroxycudraxanthone G suppressing the production of IL-8 (45% at 15.7 μg/mL in 48 hours). These results suggest that the prolonged suppression of IL-8 production by cancer cell lines is concerned in the anti-cancer activity of 8-hydroxycudraxanthone.

scholarly journals ETHNOPHARMACOLOGICAL EVALUATION OF MEDICINAL PLANTS FOR CYTOTOXICITY AGAINST VARIOUS CANCER CELL LINES

2017 ◽  
Vol 9 (5) ◽  
pp. 198 ◽  
Author(s):  
Ruchi Singh Thakur ◽  
Bharti Ahirwar
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Fruit Juice ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Phytochemical Analysis ◽  
Phyllanthus Emblica ◽  
Hydroalcoholic Extract

Objective: To evaluate the cytotoxic potential of leaves and seeds of Hibiscus sabdariffa L., fruit juice of Phyllanthus emblica, rhizomes of Dryopteris cochleata and flowers of Caesalpinia decapetala (Roth) Alston along with the chemical profiling of the most toxic extract through Gas-mass spectroscopy-MS technique.Methods: The hydroalcoholic extract of the selected crude drugs was prepared by maceration method and the extracts were undergone through phytochemical analysis. The cytotoxic activity of the hydroalcoholic extract was performed against four cancer cell lines i.e. liver (HepG2), breast (MCF7), prostate (PC-3) and leukemia (HL60) using sulphorhodamine B assay. The hydroalcoholic extract of Caesalpinia decapetala flowers was profiled through using gas mass spectroscopy.Results: The results confirmed that Phyllanthus emblica inhibited HL60 cancer cells at the dose of 35.6 µg/ml and show dose-dependent growth inhibition. The flowers of Caesalpinia decapetala inhibited nearly fifty percent of HL60 cancer cells at very low dose i. e 10 µg/ml. The analysis of Caesalpinia decapetala flowers shows the presence of diterpenoid furanolactones, bufadienolides, polycyclic enones, and androsterone.Conclusion: The fruit juice of Phyllanthus emblica and flowers of Caesalpinia decapetala showed good inhibitory activity against HL60 cancer cell line. The use of Phyllanthus emblica in herbal medicine is justified. The data obtained impelled to further assess the in vivo efficacy of Caesalpinia decapetala flowers for anticancer activity.

scholarly journals Recombinant deoxyribonucleoside kinase from Drosophila melanogaster can improve gemcitabine based combined gene/chemotherapy for targeting cancer cells

2019 ◽  
Author(s):  
Mahak Fatima ◽  
M. Mubasshar Iqbal Ahmed ◽  
Faiza Batool ◽  
Anjum Riaz ◽  
Moazzam Ali ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Nucleoside Analogs ◽  
Cancer Cell Lines ◽  
Control Group ◽  
Wide Range

A recombinant deoxyribonucleoside kinase from Drosophila melanogaster with a deletion of the last 20 amino acid residues (named DmdNKΔC20) was hypothesized as a potential therapeutic tool for gene therapy due to its broad substrate specificity and better catalytic efficiency towards nucleosides and nucleoside analogs. This study was designed to evaluate the effect of DmdNKΔC20 for sensitizing human cancer cell lines towards gemcitabine and to further investigate its role in reversal of acquired drug resistance in gemcitabine-resistant cancer cell line. The DmdNKΔC20 gene was delivered to three different cancer cell lines, including breast, colon and liver cancer cells, using lipid-mediated transfection reagent. After transfection, gene expression of DmdNKΔC20 was confirmed by reverse transcription quantitative PCR (qRT-PCR) and the combined effect of DmdNKΔC20 and gemcitabine based cytotoxicity was observed by cell viability assay. We further evolved a gemcitabine-resistant breast cancer cell line (named MCF7-R) through directed evolution in the laboratory, which showed 375-fold more resistance compared to parental MCF7 cells. Upon transfection with DmdNKΔC20 gene, MCF7-R cells showed 83-fold higher sensitivity to gemcitabine compared to the control group of MCF7-R cells. Moreover, we observed 79% higher expression of p21 protein in transfected MCF7-R cells, which may indicate induction of apoptosis. Our findings highlight the importance and therapeutic potential of DmdNKΔC20 in combined gene/chemotherapy approach to target a wide range of cancers, particularly gemcitabine-resistant cancers.

scholarly journals Identification of copy number variations and translocations in cancer cells from Hi-C data

2017 ◽  
Author(s):  
Abhijit Chakraborty ◽  
Ferhat Ay
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Copy Number ◽  
De Novo ◽  
3D Structure ◽  
Cancer Cell Lines ◽  
Copy Number Variations ◽  
Genomic Rearrangements ◽  
Link Type

AbstractMotivationEukaryotic chromosomes adapt a complex and highly dynamic three-dimensional (3D) structure, which profoundly affects different cellular functions and outcomes including changes in epigenetic landscape and in gene expression. Making the scenario even more complex, cancer cells harbor chromosomal abnormalities (e.g., copy number variations (CNVs) and translocations) altering their genomes both at the sequence level and at the level of 3D organization. High-throughput chromosome conformation capture techniques (e.g., Hi-C), which are originally developed for decoding the 3D structure of the chromatin, provide a great opportunity to simultaneously identify the locations of genomic rearrangements and to investigate the 3D genome organization in cancer cells. Even though Hi-C data has been used for validating known rearrangements, computational methods that can distinguish rearrangement signals from the inherent biases of Hi-C data and from the actual 3D conformation of chromatin, and can precisely detect rearrangement locations de novo have been missing.ResultsIn this work, we characterize how intra and inter-chromosomal Hi-C contacts are distributed for normal and rearranged chromosomes to devise a new set of algorithms (i) to identify genomic segments that correspond to CNV regions such as amplifications and deletions (HiCnv), (ii) to call inter-chromosomal translocations and their boundaries (HiCtrans) from Hi-C experiments, and (iii) to simulate Hi-C data from genomes with desired rearrangements and abnormalities (AveSim) in order to select optimal parameters for and to benchmark the accuracy of our methods. Our results on 10 different cancer cell lines with Hi-C data show that we identify a total number of 105 amplifications and 45 deletions together with 90 translocations, whereas we identify virtually no such events for two karyotypically normal cell lines. Our CNV predictions correlate very well with whole genome sequencing (WGS) data among chromosomes with CNV events for a breast cancer cell line (r=0.89) and capture most of the CNVs we simulate using Avesim. For HiCtrans predictions, we report evidence from the literature for 30 out of 90 translocations for eight of our cancer cell lines. Further-more, we show that our tools identify and correctly classify relatively understudied rearrangements such as double minutes (DMs) and homogeneously staining regions (HSRs).ConclusionsConsidering the inherent limitations of existing techniques for karyotyping (i.e., missing balanced rearrangements and those near repetitive regions), the accurate identification of CNVs and translocations in a cost-effective and high-throughput setting is still a challenge. Our results show that the set of tools we develop effectively utilize moderately sequenced Hi-C libraries (100-300 million reads) to identify known and de novo chromosomal rearrangements/abnormalities in well-established cancer cell lines. With the decrease in required number of cells and the increase in attainable resolution, we believe that our framework will pave the way towards comprehensive mapping of genomic rearrangements in primary cells from cancer patients using Hi-C.AvailabilityCNV calling: https://github.com/ay-lab/HiCnvTranslocation calling: https://github.com/ay-lab/HiCtransHi-C simulation: https://github.com/ay-lab/AveSim

scholarly journals Autophagy inhibition enhances Matrine derivative MASM induced apoptosis in cancer cells via a mechanism involving reactive oxygen species-mediated PI3K/Akt/mTOR and Erk/p38 signaling

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuming Zou ◽  
Melika Sarem ◽  
Shengnan Xiang ◽  
Honggang Hu ◽  
Weidong Xu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Reactive Oxygen ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Oxygen Species ◽  
Induced Apoptosis

Abstract Background In the quest for new anti-cancer drugs, the drug discovery process has shifted to screening of active ingredients in traditional eastern medicine. Matrine is an active alkaloid isolated from plants of the Sophora genus used in traditional Chinese herbal medicine that exhibits a wide spectrum of biological properties and has a potential as an anti-proliferative agent. In this study, we investigated the anticancer property of MASM, ([(6aS, 10S, 11aR, 11bR, 11cS)210-Methylamino-dodecahydro-3a, 7a-diaza-benzo (de)anthracene-8-thione]), a potent derivative of matrine. Methods Four epithelial cancer cell lines representing the dominant cancers, namely: A549 (non-small-cell lung cancer cell line), MCF-7 and MDA-MB-231 (breast cancer cell lines), and Hela (cervical cancer cell line) were employed, and the mechanistic underpinning of MASM-induced apoptosis was investigated using flow cytometry, western blot and immunofluorescence. Results MASM, induced apoptosis via caspase 3 dependent and independent pathways, and autophagy in all the four cancer cell lines, but post-EMT (epithelial mesenchymal transition) cells showed greater sensitivity to MASM. Scavenging reactive oxygen species using N-acetylcysteine rescued all cancer cell lines from apoptosis and autophagy. Mechanistic analysis revealed that MASM induced autophagy involves inhibition of Akt signaling and the activation of Erk and p38 signaling, and inhibition of autophagy further enhanced the apoptosis induced by MASM. Conclusions These results indicate that MASM possesses potency against cancer cells and modulating autophagy during MASM administration could be used to further enhance its therapeutic effects.

scholarly journals ALDH1A2 Is a Candidate Tumor Suppressor Gene in Ovarian Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1553
Author(s):  
Jung-A Choi ◽  
Hyunja Kwon ◽  
Hanbyoul Cho ◽  
Joon-Yong Chung ◽  
Stephen M. Hewitt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Dna Methyltransferase ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Ovarian Cancer Cell Lines

Aldehyde dehydrogenase 1 family member A2 (ALDH1A2) is a rate-limiting enzyme involved in cellular retinoic acid synthesis. However, its functional role in ovarian cancer remains elusive. Here, we found that ALDH1A2 was the most prominently downregulated gene among ALDH family members in ovarian cancer cells, according to complementary DNA microarray data. Low ALDH1A2 expression was associated with unfavorable prognosis and shorter disease-free and overall survival for ovarian cancer patients. Notably, hypermethylation of ALDH1A2 was significantly higher in ovarian cancer cell lines when compared to that in immortalized human ovarian surface epithelial cell lines. ALDH1A2 expression was restored in various ovarian cancer cell lines after treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Furthermore, silencing DNA methyltransferase 1 (DNMT1) or 3B (DNMT3B) restored ALDH1A2 expression in ovarian cancer cell lines. Functional studies revealed that forced ALDH1A2 expression significantly impaired the proliferation of ovarian cancer cells and their invasive activity. To the best of our knowledge, this is the first study to show that ALDH1A2 expression is regulated by the epigenetic regulation of DNMTs, and subsequently that it might act as a tumor suppressor in ovarian cancer, further suggesting that enhancing ALDH1A2-linked signaling might provide new opportunities for therapeutic intervention in ovarian cancer.

scholarly journals VRK1 is required in VRK2-methylated cancers of the nervous system

2021 ◽  
Author(s):  
Jonathan So ◽  
Nathaniel Mabe ◽  
Bernhard Englinger ◽  
Maria Trissal ◽  
Daeun Jeong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Damage ◽  
Nervous System ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Synthetic Lethal ◽  
Genome Scale

Collateral lethality occurs when loss of one paralog renders cancer cells dependent on the remaining paralog. Combining genome scale CRISPR/Cas9 screens coupled with RNA-sequencing in over 900 cancer cell lines, we found that cancers of nervous system lineage, including adult and pediatric gliomas and neuroblastomas, required the nuclear kinase Vaccinia-Related Kinase 1 (VRK1) for their survival. VRK1 dependency was inversely correlated with expression of its paralog VRK2. VRK2 knockout (KO) sensitized cells to VRK1 suppression, and conversely, VRK2 overexpression increased cell fitness in the setting of VRK1 suppression. DNA methylation of the VRK2 promoter was associated with low VRK2 expression in human neuroblastomas, and adult and pediatric gliomas. Mechanistically, depletion of VRK1 reduced Barrier-to-Autointegration Factor (BAF) phosphorylation during mitosis, resulting in DNA damage and apoptosis. Together, these studies identify VRK1 as a synthetic lethal target in VRK2 promoter-methylated adult and pediatric gliomas and neuroblastomas.

scholarly journals Computational correction of copy-number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells

2017 ◽  
Author(s):  
Robin M. Meyers ◽  
Jordan G. Bryan ◽  
James M. McFarland ◽  
Barbara A. Weir ◽  
Ann E. Sizemore ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Dna Cleavage ◽  
False Positive ◽  
Copy Number ◽  
Specific Effect ◽  
Cancer Cell Lines ◽  
Genome Scale ◽  
Positive Results

The CRISPR-Cas9 system has revolutionized gene editing both on single genes and in multiplexed loss-of-function screens, enabling precise genome-scale identification of genes essential to proliferation and survival of cancer cells. However, previous studies reported that an anti-proliferative effect of Cas9-mediated DNA cleavage confounds such measurement of genetic dependency, particularly in the setting of copy number gain1-4. We performed genome-scale CRISPR-Cas9 essentiality screens on 342 cancer cell lines and found that this effect is common to all lines, leading to false positive results when targeting genes in copy number amplified regions. We developed CERES, a computational method to estimate gene dependency levels from CRISPR-Cas9 essentiality screens while accounting for the copy-number-specific effect, as well as variable sgRNA activity. We applied CERES to sets of screens performed with different sgRNA libraries and found that it reduces false positive results and provides meaningful estimates of sgRNA activity. As a result, the application of CERES improves confidence in the interpretation of genetic dependency data from CRISPR-Cas9 essentiality screens of cancer cell lines.

scholarly journals A STUDY ON ANTI-CANCEROUS CAPABILITIES OF PTP7 ON DIFFERENT CELL LINES BY MTT ASSAY

2020 ◽  
pp. 3-9
Author(s):  
N. Trivikram ◽  
S. P. Sreedharbhattar
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mtt Assay ◽  
Tyrosine Phosphatase ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Protein Tyrosine ◽  
Breast And Prostate Cancer

In the present cancer advancing days, scientic investigation was catch up in studying the protein peptides involving in signalling pathways in regulating cancer cell lines development and proliferation. In our current we focused on an essential peptide protein tyrosine phosphatase, which plays an important role in signalling path way. This work evaluated the efciency of PTP7 against 3 cancer cell lines renal, breast and prostate cancer lines by MTT assay. PTP 7 on Renal cancer cell line (HTB9) shown 73.660%, breast cancer cells (MFC-7) shown 79.313% and Prostate cancer cells (PC-3) shown 87.559 % of viability by MTTassay. The advancing of protein tyrosine protease is concluded to have good viability over can cell lines, as it can further investigated in controlling of cancer.

scholarly journals Novel Marine Secondary Metabolites Worthy of Development as Anticancer Agents: A Review

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5769
Author(s):  
Florence Nwakaego Mbaoji ◽  
Justus Amuche Nweze ◽  
Liyan Yang ◽  
Yangbin Huang ◽  
Shushi Huang ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Marine Natural Products ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Wide Range

Secondary metabolites from marine sources have a wide range of biological activity. Marine natural products are promising candidates for lead pharmacological compounds to treat diseases that plague humans, including cancer. Cancer is a life-threatening disorder that has been difficult to overcome. It is a long-term illness that affects both young and old people. In recent years, significant attempts have been made to identify new anticancer drugs, as the existing drugs have been useless due to resistance of the malignant cells. Natural products derived from marine sources have been tested for their anticancer activity using a variety of cancer cell lines derived from humans and other sources, some of which have already been approved for clinical use, while some others are still being tested. These compounds can assault cancer cells via a variety of mechanisms, but certain cancer cells are resistant to them. As a result, the goal of this review was to look into the anticancer potential of marine natural products or their derivatives that were isolated from January 2019 to March 2020, in cancer cell lines, with a focus on the class and type of isolated compounds, source and location of isolation, cancer cell line type, and potency (IC50 values) of the isolated compounds that could be a guide for drug development.

Sign in / Sign up

Export Citation Format

Share Document