scholarly journals The modulation of serine metabolism in hepatoma 3924A during different phases of cellular proliferation in culture

1987 ◽  
Vol 245 (2) ◽  
pp. 609-612 ◽  
Author(s):  
K Snell ◽  
Y Natsumeda ◽  
G Weber
Keyword(s):  
Nucleic Acids ◽  
Cancer Cells ◽  
Growth Phase ◽  
Cellular Proliferation ◽  
Hepatoma Cells ◽  
Serine Hydroxymethyltransferase ◽  
Phosphoglycerate Dehydrogenase ◽  
Serine Metabolism

The activities of 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase increased markedly during the transition of hepatoma cells from a resting non-proliferating culture into the proliferating growth phase. Activities declined as cells reached confluency and entered the plateau growth phase. This pattern was paralleled by changes in [14C]serine incorporation into nucleic acids. The experiments support the hypothesis that the biosynthesis of serine is metabolically coupled to its utilization for nucleotide precursor formation in cancer cells.

scholarly journals Enzymic imbalance in serine metabolism in rat hepatomas

1986 ◽  
Vol 233 (2) ◽  
pp. 617-620 ◽  
Author(s):  
K Snell ◽  
G Weber
Keyword(s):  
Cancer Cells ◽  
Serine Hydroxymethyltransferase ◽  
Cell Renewal ◽  
Regenerating Liver ◽  
High Cell ◽  
Serine Dehydratase ◽  
Phosphoglycerate Dehydrogenase ◽  
Serine Biosynthesis ◽  
Serine Metabolism

The activity of 3-phosphoglycerate dehydrogenase was high in tissues of high cell-renewal capacity, and was increased in neonatal and regenerating liver and, more markedly, in hepatomas. Serine hydroxymethyltransferase activity was present in hepatomas, whereas other enzymes of serine utilization (serine dehydratase and serine aminotransferase) were absent. This enzymic imbalance couples serine biosynthesis preferentially to nucleotide precursor formation in cancer cells.

627: Multitarget Gene Inhibition by Synthetic Nucleic Acids in Bladder Cancer Cells

2006 ◽  
Vol 175 (4S) ◽  
pp. 202-202 ◽  
Author(s):  
Yvonne Burmeister ◽  
Kai Kraemer ◽  
Susanne Fuessel ◽  
Matthias Kotzsch ◽  
Axel Meye ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Nucleic Acids ◽  
Cancer Cells ◽  
Bladder Cancer Cells ◽  
Gene Inhibition

The KLF6 Super Enhancer Modulates Cell Proliferation via MiR-1301 in Human Hepatoma Cells

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 64-69 ◽  
Author(s):  
KumChol Ri ◽  
Chol Kim ◽  
CholJin Pak ◽  
PhyongChol Ri ◽  
HyonChol Om
Keyword(s):  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Hepatoma Cells ◽  
Regulation Mechanism ◽  
Dependent Manner ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Over Expression ◽  
Super Enhancer ◽  
Engineering Changes

Background: Recent studies have attempted to elucidate the function of super enhancers by means of microRNAs. Although the functional outcomes of miR-1301 have become clearer, the pathways that regulate the expressions of miR-1301 remain unclear. Objective: The objective of this paper was to consider the pathway regulating expression of miR- 1301 and miR-1301 signaling pathways with the inhibition of cell proliferation. Methods: In this study, we prepared the cell clones that the KLF6 super enhancer was deleted by means of the CRISPR/Cas9 system-mediated genetic engineering. Changes in miR-1301 expression after the deletion of the KLF6 super enhancer were evaluated by RT-PCR analysis, and the signal pathway of miR-1301 with inhibition of the cell proliferation was examined using RNA interference technology. Results: The results showed that miR-1301 expression was significantly increased after the deletion of the KLF6 super enhancer. Over-expression of miR-1301 induced by deletion of the KLF6 super enhancer also regulated the expression of p21 and p53 in human hepatoma cells. functional modeling of findings using siRNA specific to miR-1301 showed that expression level changes had direct biological effects on cellular proliferation in Human hepatoma cells. Furthermore, cellular proliferation assay was shown to be directly associated with miR-1301 levels. Conclusion: As a result, it was demonstrated that the over-expression of miR-1301 induced by the disruption of the KLF6 super enhancer leads to a significant inhibition of proliferation in HepG2 cells. Moreover, it was demonstrated that the KLF6 super enhancer regulates the cell-proliferative effects which are mediated, at least in part, by the induction of p21and p53 in a p53-dependent manner. Our results provide the functional significance of miR-1301 in understanding the transcriptional regulation mechanism of the KLF6 super enhancer.

scholarly journals The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 501
Author(s):  
So Hyun Park ◽  
Ji-Young Hong ◽  
Hyen Joo Park ◽  
Sang Kook Lee
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Antiproliferative Activity ◽  
Hepatoma Cells ◽  
Phase Cell ◽  
Human Hepatoma Cells ◽  
Cycle Arrest ◽  
Growth Inhibitory Activity ◽  
M Phase

Oxypeucedanin (OPD), a furocoumarin compound from Angelica dahurica (Umbelliferae), exhibits potential antiproliferative activities in human cancer cells. However, the underlying molecular mechanisms of OPD as an anticancer agent in human hepatocellular cancer cells have not been fully elucidated. Therefore, the present study investigated the antiproliferative effect of OPD in SK-Hep-1 human hepatoma cells. OPD effectively inhibited the growth of SK-Hep-1 cells. Flow cytometric analysis revealed that OPD was able to induce G2/M phase cell cycle arrest in cells. The G2/M phase cell cycle arrest by OPD was associated with the downregulation of the checkpoint proteins cyclin B1, cyclin E, cdc2, and cdc25c, and the up-regulation of p-chk1 (Ser345) expression. The growth-inhibitory activity of OPD against hepatoma cells was found to be p53-dependent. The p53-expressing cells (SK-Hep-1 and HepG2) were sensitive, but p53-null cells (Hep3B) were insensitive to the antiproliferative activity of OPD. OPD also activated the expression of p53, and thus leading to the induction of MDM2 and p21, which indicates that the antiproliferative activity of OPD is in part correlated with the modulation of p53 in cancer cells. In addition, the combination of OPD with gemcitabine showed synergistic growth-inhibitory activity in SK-Hep-1 cells. These findings suggest that the anti-proliferative activity of OPD may be highly associated with the induction of G2/M phase cell cycle arrest and upregulation of the p53/MDM2/p21 axis in SK-HEP-1 hepatoma cells.

scholarly journals Supercritical Fluid Extraction of Citrus iyo Hort. ex Tanaka Pericarp Inhibits Growth and Induces Apoptosis Through Abrogation of STAT3 Regulated Gene Products in Human Prostate Cancer Xenograft Mouse Model

2016 ◽  
Vol 16 (2) ◽  
pp. 227-243 ◽  
Author(s):  
Chulwon Kim ◽  
Il Ho Lee ◽  
Ho Bong Hyun ◽  
Jong-Chan Kim ◽  
Rajendra Gyawali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cellular Proliferation ◽  
Human Prostate ◽  
Parp Cleavage ◽  
G1 Arrest ◽  
Gene Products ◽  
Human Prostate Cancer ◽  
Male Mice

Activation of signal transducer and activator of transcription 3 (STAT3) is well known to play a major role in the cell growth, survival, proliferation, metastasis, and angiogenesis of various cancer cells. Most of the citrus species offer large quantities of phytochemicals that have beneficial effects attributed to their chemical components. Our study was carried out to evaluate the anticancer effects of the pericarp of Iyokan ( Citrus iyo Hort. ex Tanaka), locally known as yeagam in Korea, through modulation of the STAT3 signaling pathway in both tumor cells and a nude mice model. The effect of supercritical extracts of yeagam peel (SEYG) on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was examined. The in vivo effect of SEYG on the growth of DU145 human prostate xenograft tumors in athymic nu/nu male mice was also investigated. We found SEYG exerted substantial inhibitory effect on STAT3 activation in human prostate cancer DU145 cells as compared to other tumor cells analyzed. SEYG inhibited proliferation and downregulated the expression of various STAT3-regulated gene products such as bcl-2, bcl-xL, survivin, IAP-1/2, cyclin D1, cyclin E, COX-2, VEGF, and MMP-9. This correlated with an increase in apoptosis as indicated by an increase in the expression of p53 and p21 proteins, the sub-G1 arrest, and caspase-3-induced PARP cleavage. When administered intraperitoneally, SEYG reduced the growth of DU145 human prostate xenograft tumors through downmodulation of STAT3 activation in athymic nu/nu male mice. Overall, these results suggest that SEYG extract has the potential source of STAT3 inhibitors that may have a potential in chemoprevention of human prostate cancer cells.

Extraction of ursolic acid from Ocimum sanctum and synthesis of its novel derivatives: effects on extracellular homocysteine, dihydrofolate reductase activity and proliferation of HepG2 human hepatoma cells

Pteridines ◽  
2013 ◽  
Vol 24 (3) ◽  
pp. 191-199 ◽  
Author(s):  
Apsara Batra ◽  
V. Girija Sastry
Keyword(s):  
Cancer Cells ◽  
Ursolic Acid ◽  
Dihydrofolate Reductase ◽  
Carbon Metabolism ◽  
Hepatoma Cells ◽  
Ocimum Sanctum ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Anti Cancer ◽  
One Carbon Metabolism

AbstractThe objective of the present study was to extract ursolic acid (UA) from Ocimum sanctum, to synthesize its bioactive derivatives, evaluate the anti-cancer effect of its derivatives and to establish the possible mechanism of action. In the present report, we extracted UA from whole plant of O. sanctum, synthesized its novel derivatives and investigated their effect on homocysteine metabolism and dihydrofolate reductase (DHFR) activity of HepG2 cells. UA and its derivatives UA-1, UA-2 and UA-3 down-regulated DHFR activity and increased extracellular homocysteine. UA-2 showed significant anti-proliferation activity in cancer cells. Cancer cells have increased the requirement of pyrimidine base thymidylate due to rapid cell division. Thymidylate biosynthesis depends on sufficient pools of folate dependent enzymes like DHFR. In the present study, we examined the UA and its derivatives mediated perturbation of DHFR activity and extracellular homocysteine in HepG2 human hepatoma cells. After incubation with UA-2, a potent inhibition of DHFR activity was observed. Our results showed that derivatization of UA might adversely affect DHFR activity. Measurement of extracellular homocysteine indicated impaired one-carbon metabolism in cells treated with UA derivatives. In conclusion, our data suggest an anti-cancer role of UA and its derivatives via inhibition of one-carbon metabolism.

932 Targeting the 19S Proteasomal Subunit, Rpt4, in Colon Cancer Cells Induces Cell Death and Reduces Cellular Proliferation In Vitro and In Vivo

2013 ◽  
Vol 144 (5) ◽  
pp. S-166-S-167
Author(s):  
Karen Boland ◽  
Caoimhin Concannon ◽  
Niamh McCawley ◽  
Elaine W. Kay ◽  
Deborah McNamara ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Colon Cancer Cells ◽  
Proliferation In Vitro

scholarly journals Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin

2021 ◽  
Vol 118 (5) ◽  
pp. e2020478118
Author(s):  
Tobias Wijshake ◽  
Zhongju Zou ◽  
Beibei Chen ◽  
Lin Zhong ◽  
Guanghua Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Beclin 1 ◽  
Beta Catenin ◽  
A Genome ◽  
E Cadherin

Beclin 1, an autophagy and haploinsufficient tumor-suppressor protein, is frequently monoallelically deleted in breast and ovarian cancers. However, the precise mechanisms by which Beclin 1 inhibits tumor growth remain largely unknown. To address this question, we performed a genome-wide CRISPR/Cas9 screen in MCF7 breast cancer cells to identify genes whose loss of function reverse Beclin 1-dependent inhibition of cellular proliferation. Small guide RNAs targeting CDH1 and CTNNA1, tumor-suppressor genes that encode cadherin/catenin complex members E-cadherin and alpha-catenin, respectively, were highly enriched in the screen. CRISPR/Cas9-mediated knockout of CDH1 or CTNNA1 reversed Beclin 1-dependent suppression of breast cancer cell proliferation and anchorage-independent growth. Moreover, deletion of CDH1 or CTNNA1 inhibited the tumor-suppressor effects of Beclin 1 in breast cancer xenografts. Enforced Beclin 1 expression in MCF7 cells and tumor xenografts increased cell surface localization of E-cadherin and decreased expression of mesenchymal markers and beta-catenin/Wnt target genes. Furthermore, CRISPR/Cas9-mediated knockout of BECN1 and the autophagy class III phosphatidylinositol kinase complex 2 (PI3KC3-C2) gene, UVRAG, but not PI3KC3-C1–specific ATG14 or other autophagy genes ATG13, ATG5, or ATG7, resulted in decreased E-cadherin plasma membrane and increased cytoplasmic E-cadherin localization. Taken together, these data reveal previously unrecognized cooperation between Beclin 1 and E-cadherin–mediated tumor suppression in breast cancer cells.

miR-340 Restrains the Growth of Lung Cancer Cells Through Mitogen-Activated Protein Kinase (MAPK) Signaling

2021 ◽  
Vol 11 (5) ◽  
pp. 963-969
Author(s):  
Wenhong Zheng ◽  
Wenrui Xie ◽  
Lijuan Fu ◽  
Zhengqi Fu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Lung Cancer Cells ◽  
Luciferase Assay ◽  
Knock Out ◽  
Novel Target

The lung cancer was most deadly tumor in the world and the suvival rate needs to be improved clinically and urgently. The abnormal miR-340 expression is found in several solid tumors. Our study was aimed to explore miR-340’s role in lung cancer. 14 cases of patients with lung cancer was selected to measure miR-340 level by RT-PCR and analyze its correlation with clinical characteristics. The relation between the miR-340 and DICER1 was detected by dual luciferase assay and cell proliferation was measured by MTT assay along with analysis of cell migration and invasive by Scratch-Wound experiment. The miR-340 in lung cancer cells was reduced significantly and DICER1 was predicted to be a potential target of miR-340. DICER1 level was found to be negatively related with miR-340 level. The DICER1 as the direct target gene of miR-340 was conducive to improve miR-340 function through overexpression and knock-out experiment further. Abnormal miR-340 level affected lung cancer cell proliferation and migration as well as MAPK signaling. miR-340 could affect the biological morphology and transformation of physiological function of lung cancer cells mainly through restraining the expression of apoptosis and prompting the cellular proliferation, indicating that it might be a novel target to improve the treatment of lung cancer.

Gene therapy promises accurate, targeted administration and overcoming drug resistance in diverse cancer cells

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Drug Resistance ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Clinical Research ◽  
Cancer Cells ◽  
Cationic Lipids ◽  
Target Cells ◽  
Genetic Components ◽  
Wide Range

Nucleic acid-based therapeutics such as siRNA and miRNA employ the silencing capabilities of the RNAi mechanism to affect the expression of one gene or several genes in target cells. Nucleic acid-based therapies enable accurate, targeted administration and overcoming drug resistance in diverse cancer cells. Several studies have shown that they can be utilized alongside pharmacological therapy to increase the efficacy of existing therapies. In addition, nucleic acid-based therapies have the potential to widen the spectrum of druggable targets for a range of diseases and emerge as a novel therapeutic technique for treating a number of diseases that are today untreatable. Nucleic acids are dependent on their effective distribution to target cells, which need correct complexation and encapsulation in a delivery mechanism. Although nucleic acids exist in a variety of forms and sizes, their physical and chemical commonality allow them to be loaded into a wide range of delivery vehicles. The primary biomaterials used to encapsulate genetic components were cationic lipids and polymers. Furthermore, the experiments focused particularly on effective transfection in target cells.Recent breakthroughs in NP-based RNA therapeutics have spurred a flood of clinical research, facing many challenges. In vivo, pharmacokinetics of different RNA-based medications must be researched to establish the viability and therapeutic potential of nucleic acid-based therapeutics. The U.S. Food and Drug Administration recently authorized many NP-based gene therapy. In 2019, Novartis authorized Zolgensma (onasemnogene abeparvovec-xioi) to treat spinal muscle atrophy. The first clinical research employing siRNA began in 2004 and is considered a milestone in nucleic acid-based drug development. Thirty clinical investigations have subsequently been completed. In 2018, the US FDA cleared Onpattro (Patisiran, Alnylam Pharmaceuticals) for the treatment of polyneuropathy caused by transthyretin amyloidosis.Several new generations of nucleic acid compositions employing polymer nanoparticles or liposomes are presently undergoing clinical testing. If allowed, the debut of nucleic acid-based treatments would represent a watershed event in immunotherapy. Advances in the design and development of biocompatible nanomaterials would allow us to overcome the above-mentioned problems and so show the potential to deliver nucleic acids in the treatment of a number of illnesses.

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