scholarly journals Singular v Dual inhibition of SNF2L and its isoform, SNF2LT, have similar effects on DNA Damage but opposite effects on the DNA Damage Response, Cancer Cell Growth Arrest and Apoptosis

Oncotarget ◽  
2012 ◽  
Vol 3 (4) ◽  
pp. 475-489 ◽  
Author(s):  
Yin Ye ◽  
Yi Xiao ◽  
Wenting Wang ◽  
Jian-Xin Gao ◽  
Kurtis Yearsley ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Growth ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Growth Arrest ◽  
Cancer Cell Growth ◽  
Cell Growth Arrest ◽  
Damage Response ◽  
Dual Inhibition

scholarly journals Phosphoinositide 3-Kinase (PI3K) Reactive Oxygen Species (ROS)-Activated Prodrug in Combination with Anthracycline Impairs PI3K Signaling, Increases DNA Damage Response and Reduces Breast Cancer Cell Growth

2021 ◽  
Vol 22 (4) ◽  
pp. 2088
Author(s):  
Rosalin Mishra ◽  
Long Yuan ◽  
Hima Patel ◽  
Aniruddha S. Karve ◽  
Haizhou Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Cell Growth ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cancer Cell Growth ◽  
Damage Response

RIDR-PI-103 is a novel reactive oxygen species (ROS)-induced drug release prodrug with a self-cyclizing moiety linked to a pan-PI3K inhibitor (PI-103). Under high ROS, PI-103 is released in a controlled manner to inhibit PI3K. The efficacy and bioavailability of RIDR-PI-103 in breast cancer remains unexplored. Cell viability of RIDR-PI-103 was assessed on breast cancer cells (MDA-MB-231, MDA-MB-361 and MDA-MB-453), non-tumorigenic MCF10A and fibroblasts. Matrigel colony formation, cell proliferation and migration assays examined the migratory properties of breast cancers upon treatment with RIDR-PI-103 and doxorubicin. Western blots determined the effect of doxorubicin ± RIDR-PI-103 on AKT activation and DNA damage response. Pharmacokinetic (PK) studies using C57BL/6J mice determined systemic exposure (plasma concentrations and overall area under the curve) and T1/2 of RIDR-PI-103. MDA-MB-453, MDA-MB-231 and MDA-MB-361 cells were sensitive to RIDR-PI-103 vs. MCF10A and normal fibroblast. Combination of doxorubicin and RIDR-PI-103 suppressed cancer cell growth and proliferation. Doxorubicin with RIDR-PI-103 inhibited p-AktS473, upregulated p-CHK1/2 and p-P53. PK studies showed that ~200 ng/mL (0.43 µM) RIDR-PI-103 is achievable in mice plasma with an initial dose of 20 mg/kg and a 10 h T1/2. (4) The prodrug RIDR-PI-103 could be a potential therapeutic for treatment of breast cancer patients.

Dietary isothiocyanates inhibit cancer cell growth by inducing replication stress mediated DNA damage response

2015 ◽  
Vol 137 ◽  
pp. 65 ◽  
Author(s):  
R. Barnett ◽  
K. Tripathi ◽  
L. Bachaboina ◽  
U. Hussien ◽  
J.M. Scalici ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Growth ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Replication Stress ◽  
Cancer Cell Growth ◽  
Damage Response

scholarly journals Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer

2020 ◽  
Vol 295 (50) ◽  
pp. 17169-17186
Author(s):  
Mysore S. Veena ◽  
Santanu Raychaudhuri ◽  
Saroj K. Basak ◽  
Natarajan Venkatesan ◽  
Parameet Kumar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Dna Damage ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
S Phase ◽  
Cervical Cancer Cell ◽  
Damage Response

We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3′ terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys382-p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G1-S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors.

scholarly journals TFEB Modulates p21/WAF1/CIP1 during the DNA Damage Response

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1186 ◽  
Author(s):  
Sandra Pisonero-Vaquero ◽  
Chiara Soldati ◽  
Marcella Cesana ◽  
Andrea Ballabio ◽  
Diego Luis Medina
Keyword(s):  
Dna Damage ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Cell Types ◽  
Dependent Manner ◽  
Cancer Cell Growth ◽  
Direct Role ◽  
Growth And Survival ◽  
Damage Response ◽  
P21 Waf1

The MiT/TFE family of transcription factors (MITF, TFE3, and TFEB), which control transcriptional programs for autophagy and lysosome biogenesis have emerged as regulators of energy metabolism in cancer. Thus, their activation increases lysosomal catabolic function to sustain cancer cell growth and survival in stress conditions. Here, we found that TFEB depletion dramatically reduces basal expression levels of the cyclin-dependent kinase (CDK) inhibitor p21/WAF1 in various cell types. Conversely, TFEB overexpression increases p21 in a p53-dependent manner. Furthermore, induction of DNA damage using doxorubicin induces TFEB-mediated activation of p21, delays G2/M phase arrest, and promotes cell survival. Pharmacological inhibition of p21, instead, abrogates TFEB-mediated protection during the DNA damage response. Together, our findings uncover a novel and direct role of TFEB in the regulation of p21 expression in both steady-state conditions and during the induction of DNA-damage response (DDR). Our observations might open novel therapeutic strategies to promote cancer cell death by targeting the TFEB-p21 pathway in the presence of genotoxic agents.

Combinatorial Use of DNA Ligase Inhibitor L189 and Temozolomide Potentiates Cell Growth Arrest in HeLa

2019 ◽  
Vol 15 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Devashree Jahagirdar ◽  
Shruti Purohit ◽  
Nilesh K. Sharma
Keyword(s):  
Cell Growth ◽  
Hela Cell ◽  
Cancer Cell ◽  
Combined Treatment ◽  
Fluorescent Microscopy ◽  
Growth Arrest ◽  
Cycle Phase ◽  
Dna Ligase ◽  
Cancer Cell Growth ◽  
Cell Growth Arrest

Introduction: The issues of carcinoma drug resistance to alkylating agents such as Temozolomide (TMZ) are considered as a major concern in therapeutics. The potential ways to achieve better cancer cell growth arrest and cytotoxicity have been suggested including the combinatorial use of DNA repair protein inhibitors and genotoxic drug TMZ. Here, authors assess the ability of DNA ligase inhibitor (L189) to modulate TMZ mediated HeLa cell growth arrest and cytotoxicity. Materials and Methods: Here, authors have employed Trypan blue dye exclusion and propidium iodide (PI) using FACS to determine HeLa cell viability after exposure to TMZ with or without L189 inhibitor. Additionally, authors show the DNA ligase III protein level using ELISA and fluorescent microscopy to support the observed effects of combinatorial use of TMZ and L189. Results: In this paper, data indicate that the addition of L189 produced appreciable decrease in the growth of HeLa cells. However, combined treatment of L189 and TMZ showed enhanced TMZinduced HeLa growth arrest possibly in G2/M cell cycle phase without employing cell death mechanisms. Conclusions: These results underscore the combinatorial treatment using TMZ and L189 to bring desirable cancer cell growth arrest and future molecular study to dissect out the participating pathways.

scholarly journals Chidamide Inhibits Aerobic Metabolism to Induce Pancreatic Cancer Cell Growth Arrest by Promoting Mcl-1 Degradation

PLoS ONE ◽  
2016 ◽  
Vol 11 (11) ◽  
pp. e0166896 ◽  
Author(s):  
Mu He ◽  
Zhixin Qiao ◽  
Yanbing Wang ◽  
Qiyuan Kuai ◽  
Changlan Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Growth Arrest ◽  
Aerobic Metabolism ◽  
Cancer Cell Growth ◽  
Cell Growth Arrest
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