Elucidation of the cellular components responsive to chemotherapeutic agents as cisplatin rationalizes the strategy for anticancer chemotherapy. The removal of the cisplatin/DNA lesions gives the chance to the cancer cells to survive and compromises the chemotherapeutical treatment. Therefore, the cell repair efficiency is substantial for the clinical outcome. High mobility group box 1 (HMGB1) protein is considered to be involved in the removal of the lesions as it binds with high affinity to cisplatin/DNA adducts. We demonstrated that overexpression of HMGB1 protein inhibited cis-platinated DNA repair in vivo and the effect strongly depended on its C-terminus. We registered increased levels of DNA repair after HMGB1 silencing only in p53 defective H1299 lung cancer cells. Next, introduction of functional p53 resulted in DNA repair inhibition. H1299 cells overexpressing HMGB1 were significantly sensitized to treatment with cisplatin demonstrating the close relation between the role of HMGB1 in repair of cis-platinated DNA and the efficiency of the anticancer drug, the process being modulated by the C-terminus. In A549 cells with functional p53, the repair of cisplatin/DNA adducts is determined by а complex action of HMGB1 and p53 as an increase of DNA repair capacity was registered only after silencing of both proteins.

Download full-text PDF

Source
http://dx.doi.org/10.1093/jb/mvw012DOI Listing

Publication Analysis

Top Keywords

dna repair
16
repair
8
repair capacity
8
lung cancer
8
cancer cells
8
hmgb1 protein
8
cisplatin/dna adducts
8
cis-platinated dna
8
functional p53
8
hmgb1
7

Similar Publications

Mitochondrial Mayhem: How cigarette smoke induces placental dysfunction through MMS19 degradation.

Ecotoxicol Environ Saf

January 2025

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, PR China. Electronic address:

Cigarette smoke (CS) has detrimental effects on placental growth and embryo development, but the underlying mechanisms remain unclear. This study aims to investigate the impact of CS on trophoblast cell proliferation and regulated cell death (RCD) by examining its interference with iron-sulfur cluster (ISC) proteins and the CIA pathway. Exposure to CS disrupted the cytosolic ISC assembly (CIA) pathway, downregulated ISC proteins, and decreased ISC maturation in the placenta of rats exposed to passive smoking.

View Article and Find Full Text PDF

The increasing shift from cannabis smoking to cannabis vaping is largely driven by the perception that vaping to form an aerosol represents a safer alternative to smoking and is a form of consumption appealing to youth. Herein, we compared the chemical composition and receptor-mediated activity of cannabis smoke extract (CaSE) to cannabis vaping extract (CaVE) along with the biological response in human bronchial epithelial cells. Chemical analysis using HPLC and GC/MS revealed that cannabis vaping aerosol contained fewer toxicants than smoke; CaSE and CaVE contained teratogens, carcinogens, and respiratory toxicants.

View Article and Find Full Text PDF

Objective: This study investigates the mechanism underlying sorafenib resistance in hepatocellular carcinoma cells (HCC), focusing on DNA damage repair (DDR) pathways to develop targeted therapeutic strategies.

Methods: Bioinformatics analysis was used to screen genes associated with sorafenib resistance, which was further demonstrated by western blotting. Cell proliferation was determined using the EdU assay.

View Article and Find Full Text PDF

Colorectal cancer (CRC) is well characterized in terms of genetic mutations and the mechanisms by which they contribute to carcinogenesis. Mutations in APC, TP53, and KRAS are common in CRC, indicating key roles for these genes in tumor development and progression. However, for certain tumors with low frequencies of these mutations that are defined by tumor location and molecular phenotypes, a carcinogenic mechanism dependent on BRAF mutations has been proposed.

View Article and Find Full Text PDF

Background: Neoadjuvant combination immunotherapy is a potential treatment option for patients with proficient mismatch repair/microsatellite stable colorectal cancer. Preoperative screening via endoscopy and imaging examinations could help identify patients who may potentially achieve a complete response after neoadjuvant combination immunotherapy. This study aims to evaluate the diagnostic accuracy of endoscopic and imaging examinations in predicting pathological complete response after neoadjuvant combination immunotherapy.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!