Inhibition of cathepsin L sensitizes human glioma cells to ionizing radiation in vitro through NF-κB signaling pathway

Abstract

Aim: Cathepsin L, a lysosomal cysteine proteinase, is exclusively elevated in a variety of malignancies, including gliomas. In this study we investigated the relationship between cathepsin L and NF-κB, two radiation-responsive elements, in regulating the sensitivity of human glioma cells ionizing radiation (IR) in vitro. Methods: Human glioma U251 cells were exposed to IR (10 Gy), and the expression of cathepsin L and NF-κB was measured using Western blotting. The nuclear translocation of NF-κB p65 and p50 was analyzed with immunofluorescence assays. Cell apoptosis was examined with clonogenic assays. NF-κB transcription and NF-κB-dependent cyclin D1 and ATM transactivation were monitored using luciferase reporter and ChIP assays, respectively. DNA damage repair was investigated using the comet assay.

Cathepsin L upregulation-induced EMT phenotype is associated with the acquisition of cisplatin or paclitaxel resistance in A549 cells

“…Moreover, NF-κB can bind to the human Snail promoter in the region between -194 and -78 bp and increase the transcription of Snail [60] . Our group found that CTSL acts as an upstream regulator of NF-κB activation [61] . Thus, we suspected that the regulation of CTSL by Snail may be achieved via NF-κB or CUX1.…”

HZ08 suppresses RelB-activated MnSOD expression and enhances Radiosensitivity of prostate Cancer cells

“…NF-κB can be activated through either RelA:p50-based classical (canonical) or RelB:p52-based alternative (non-canonical) pathway by a multitude of stimulants including IR [ 14 ]. Although most studies have focused on the classical pathway [ 15 – 17 ], we and others found that RelB is uniquely expressed at the high levels in advanced PCa and the levels of nuclear RelB are particularly associated with the patients Gleason scores [ 18 , 19 ]. Additionally, as a typical NF-κB regulated protein, MnSOD is adaptively stimulated by IR-induced ROS production partially through RelB-mediated transcriptional activation, and selectively preventing RelB nuclear translocation resulted in enhancing radiosensitivity of PCa cells [ 20 ] .…”

Identification of an Autophagy-Related 10-lncRNA-mRNA Signature for Distinguishing Glioblastoma Multiforme from Lower‑Grade Glioma and Prognosis Prediction

“…Overexpression of CTSB decreased chemotherapeutic temozolomide drug-induced glioma cell death and promoted the mesenchymal transition [29]; while knockdown of CTSB caused cell cycle arrested in G0/G1 phases and enhanced radiosensitivity [30]. Elevated CTSB may, like cathepsin L, contribute to radio-resistance in human glioma cells by activation of its downstream NF-κB [31]. The expression of NF-κB1 was revealed to be increased with the increasing degree of malignancy in glioma [32].…”