Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

21 December 2016 : Laboratory Research  

Transglutaminase 2 Inhibitor KCC009 Induces p53-Independent Radiosensitization in Lung Adenocarcinoma Cells

Sheng Huaying1AC, Yao Dong2D, Zhu Chihong2B, Qian Xiaoqian2B, Wan Danying2EF, Feng Jianguo23DG*

DOI: 10.12659/MSM.901605

Med Sci Monit 2016; 22:5041-5048

Abstract

BACKGROUND: The expression of transglutaminase 2 (TG2) is correlated to DNA damage repair and apoptosis through the p53 pathway. The present study aimed to investigate the potential radiosensitization effect and possible mechanisms of the TG2 inhibitor KCC009 in lung cancer in vitro.

MATERIAL AND METHODS: A single hit multi-target model was used to plot survival curves and to calculate the sensitizing enhancement ratios in lung cancer wild-type or mutant p53 of H1299 cells. We performed analyses for changes of cell cycling and apoptotic responses of cells; Western blot analysis and real-time SYBR Green PCR assay were used to determine the changes of mRNA/protein expressions; ELISA assay was used for examination of cytochrome c release in cytoplasm.

RESULTS: Our results showed that KCC009 induced radiosensitization in both H1299/WT-p53 and H1299/M175H-p53 cells. KCC009+IR induced G0/G1 arrest in H1299/WT cells and G2/M arrest in H1299/M175H-p53 cells. KCC009+IR also induced apoptosis in both cell lines. In addition, KCC009+IR decreased the TG2 expression, and increased the p53 expression in H1299/WT cells but not in H1299/M175H-p53 cells. KCC009+IR also increased the expression of p21, Bax, p-caspase-3, and decreased Bcl-2 and CyclinD expression in H1299/WT cells. While KCC009+IR induced phosphorylation of caspase-3 and increase Cyt-C level in the cytoplasm of, and decreased CyclinB, Bcl-2 expression in H1299/M175H-p53 cells, we noticed that Cyt-C level in the nucleus decreased in the H1299/WT cells.

CONCLUSIONS: KCC009, a TG2 inhibitor, exhibits potent radiosensitization effects in human lung cancer cells expressing wild-type or mutant p53 with different mechanisms.

Keywords: Genes, p53

Add Comment 0 Comments

Editorial

01 May 2024 : Editorial  

Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)

Dinah V. Parums

DOI: 10.12659/MSM.944927

Med Sci Monit 2024; 30:e944927

In Press

07 May 2024 : Clinical Research  

Treatment of AVN-Induced Proximal Pole Scaphoid Nonunion Using a Fifth and Fourth Extensor Compartmental Ar...

Med Sci Monit In Press; DOI: 10.12659/MSM.944553  

16 Mar 2024 : Clinical Research  

Diagnostic Efficiency of ACR-TIRADS Score for Differentiating Benign and Malignant Thyroid Nodules of Vario...

Med Sci Monit In Press; DOI: 10.12659/MSM.943228  

08 May 2024 : Clinical Research  

Effect of Individualized PEEP Guided by Driving Pressure on Diaphragm Function in Patients Undergoing Lapar...

Med Sci Monit In Press; DOI: 10.12659/MSM.944022  

21 Mar 2024 : Clinical Research  

Impact of Serum Vitamin D, B6, and B12 and Cognitive Functions on Quality of Life in Peri- and Postmenopaus...

Med Sci Monit In Press; DOI: 10.12659/MSM.943249  

Most Viewed Current Articles

17 Jan 2024 : Review article  

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

16 May 2023 : Clinical Research  

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750