Faculty Opinions recommendation of Molecular interplay between mutant p53 proteins and autophagy in cancer cells.

2017 ◽  
Author(s):  
Ygal Haupt ◽  
Sue Haupt
Keyword(s):  
Cancer Cells ◽  
Mutant P53

scholarly journals Suberoylanilide hydroxamic acid enhances the radiosensitivity of lung cancer cells through acetylated wild-type and mutant p53-dependent modulation of mitochondrial apoptosis

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098154
Author(s):  
Kan Wu ◽  
Xueqin Chen ◽  
Xufeng Chen ◽  
Shirong Zhang ◽  
Yasi Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Hydroxamic Acid ◽  
Site Directed Mutagenesis ◽  
Lung Cancer Cells ◽  
Mutant P53 ◽  
Suberoylanilide Hydroxamic Acid ◽  
Mitochondrial Apoptosis ◽  
Wild Type ◽  
Clonogenic Cell

Objective Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has shown potential as a candidate radiosensitizer for many types of cancers. This study aimed to explore the radiosensitization mechanism of SAHA in lung cancer cells. Methods Mutations in p53 were generated by site-directed mutagenesis using polymerase chain reaction. Transfection was performed to generate H1299 cells carrying wild-type or mutant p53. The radiosensitizing enhancement ratio was determined by clonogenic assays. Mitochondrial apoptosis was detected using JC-1 staining and flow cytometry analysis. Results Our results showed that SAHA induced radiosensitization in H1299 cells expressing wild-type p53, p53R175H or p53P223L, but this enhanced clonogenic cell death was not observed in parental H1299 (p53-null) cells or H1299 cells expressing p53 with K120R, A161T and V274R mutations. In SAHA-sensitized cells, mitochondrial apoptosis was induced following exposure to irradiation. Additionally, we observed that a secondary mutation at K120 (K120R) could eliminate p53-mediated radiosensitization and mitochondrial apoptosis. Conclusions The results of this study suggest that wild-type and specific mutant forms of p53 mediate SAHA-induced radiosensitization by regulating mitochondrial apoptosis, and the stabilization of K120 acetylation by SAHA is the molecular basis contributing to radiosensitization in lung cancer cells.

scholarly journals Mutant p53-Notch1 Signaling Axis Is Involved in Curcumin-Induced Apoptosis of Breast Cancer Cells

2013 ◽  
Vol 17 (4) ◽  
pp. 291 ◽  
Author(s):  
Yun-Hee Bae ◽  
Jong Hyo Ryu ◽  
Hyun-Joo Park ◽  
Kwang Rok Kim ◽  
Hee-Jun Wee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mutant P53 ◽  
Notch1 Signaling ◽  
Signaling Axis ◽  
Induced Apoptosis

Mutant p53 Enhances Nuclear Factor κB Activation by Tumor Necrosis Factor α in Cancer Cells

2007 ◽  
Vol 67 (6) ◽  
pp. 2396-2401 ◽  
Author(s):  
Lilach Weisz ◽  
Alexander Damalas ◽  
Michalis Liontos ◽  
Panagiotis Karakaidos ◽  
Giulia Fontemaggi ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cancer Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nuclear Factor Κb ◽  
Mutant P53 ◽  
Nuclear Factor ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals ErbB2 inhibition by lapatinib promotes degradation of mutant p53 protein in cancer cells

Oncotarget ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 5823-5833 ◽  
Author(s):  
Dun Li ◽  
Natalia D. Marchenko
Keyword(s):  
Cancer Cells ◽  
P53 Protein ◽  
Mutant P53

scholarly journals Mutant p53 blocks SESN1/AMPK/PGC-1α/UCP2 axis increasing mitochondrial O2ˉ· production in cancer cells

2018 ◽  
Vol 119 (8) ◽  
pp. 994-1008 ◽  
Author(s):  
Marco Cordani ◽  
Giovanna Butera ◽  
Ilaria Dando ◽  
Margalida Torrens-Mas ◽  
Elena Butturini ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mutant P53

scholarly journals Synergistic Antitumor Effect of BKM120 with Prima-1Met Via Inhibiting PI3K/AKT/mTOR and CPSF4/hTERT Signaling and Reactivating Mutant P53

2018 ◽  
Vol 45 (5) ◽  
pp. 1772-1786 ◽  
Author(s):  
Zongjuan Li ◽  
Xiangdong Xu ◽  
Yizhuo Li ◽  
Kun Zou ◽  
Zhuo Zhang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Colony Formation ◽  
Antitumor Effect ◽  
Migration And Invasion ◽  
Mutant P53 ◽  
Stem Cell Markers ◽  
Combinational Treatment ◽  
Thyroid Cancer Cells

Background/Aims: PI3KCA and mutant p53 are associated with tumorigenesis and the development of cancers. NVP-BKM120, a selective pan-PI3K inhibitor, exerts the antitumor activity by suppressing the PI3K signaling pathway. Prima-1Met, a low molecular weight compound, can rescue the gain-of-function of mutant p53 by restoring its transcriptional function. In this study, we investigated whether PI3K inhibition combined with mutant p53 reactivation could enhance the antitumor effect in thyroid cancer cells. Methods: The effects of BKM120 and Prima-1Met on the proliferation, apoptosis, migration and invasion of thyroid cancer cells were measured by MTT, colony formation, flow cytometry, wound-healing and transwell assays, respectively. Thyroid differentiation was assessed by detecting the expression levels of specific markers using RT-PCR and Western blot. The in vivo antitumor efficacy was analyzed in a mouse xenograft model. Results: The combinational treatment of BKM120 and Prima-1Met significantly enhanced the inhibitions of cell viability, colony formation, migration and invasion, and the induction of apoptosis in thyroid cell lines, and synergistically suppressed tumor xenograft growth by inhibiting the PI3K/Akt/mTOR and EMT signaling pathways, up-regulating p53 targeted genes, and triggering the release of cytochrome c. Moreover, the combination of BKM120 and Prima-1Met suppressed the stemlike traits of thyroid cancer cells and promoted their differentiation by upregulating the expression of thyroid-specific differentiation markers and repressing the expression of cancer stem cell markers. Furthermore, the mechanism study demonstrated that the combinational treatment synergistically abrogated the binding of CPSF4 at the promoter of hTERT and thus suppressed hTERT expression. Consistently, overexpression of hTERT rescued the inhibitions of cell viability, invasion and stem-like traits mediated by the combination of BKM120 and Prima-1Met. Conclusion: Our results showed that the combination of BKM120 with Prima-1Met synergistically suppressed the growth of thyroid cancer cells and tumor xenografts via inhibiting PI3K/Akt/mTOR and CPSF4/hTERT signaling and reactivating mutant p53.

Abstract 2472: Small-molecule-induced reactivation of mutant p53 in cancer cells.

2013 ◽  
Author(s):  
Xiangrui Liu ◽  
Rainer Wilcken ◽  
Andreas Joerger ◽  
Irina Chuckowree ◽  
John Spencer ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Small Molecule ◽  
Mutant P53
Sign in / Sign up

Export Citation Format

Share Document