• Home
  • Search Results
  • ROS-p53-cyclophilin-D signaling mediates salinomycin-induced glioma cell necrosis.

ROS-p53-cyclophilin-D signaling mediates salinomycin-induced glioma cell necrosis.

Journal of experimental & clinical cancer research : CR (2015-05-31)
Li-sen Qin, Pi-feng Jia, Zhi-qing Zhang, Shi-ming Zhang
ABSTRACT

The primary glioblastoma multiforme (GBM) is the most malignant form of astrocytic tumor with an average survival of approximately 12-14 months. The search for novel and more efficient chemo-agents against this disease is urgent. Salinomycin induces broad anti-cancer effects; however, its role in GBM and the underlying mechanism are not clear. Here we found that salinomycin induced both apoptosis and necrosis in cultured glioma cells, and necrosis played a major role in contributing salinomycin's cytotoxicity. Salinomycin induced p53 translocation to mitochondria, where it formed a complex with cyclophilin-D (CyPD). This complexation was required for mitochondrial permeability transition pore (mPTP) opening and subsequent programmed necrosis. Blockade of Cyp-D by siRNA-mediated depletion or pharmacological inhibitors (cyclosporin A and sanglifehrin A) significantly suppressed salinomycin-induced glioma cell necrosis. Meanwhile, p53 stable knockdown alleviated salinomycin-induced necrosis in glioma cells. Reactive oxygen species (ROS) production was required for salinomycin-induced p53 mitochondrial translocation, mPTP opening and necrosis, and anti-oxidants n-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) inhibited p53 translocation, mPTP opening and glioma cell death. Thus, salinomycin mainly induces programmed necrosis in cultured glioma cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
HEPES, ≥99.5% (titration)
Sigma-Aldrich
Trypan Blue solution, 0.4%, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Sucrose, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, 98%
Sigma-Aldrich
HEPES, BioPerformance Certified, ≥99.5% (titration), suitable for cell culture
Sigma-Aldrich
Propidium iodide, ≥94.0% (HPLC)
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
Sigma-Aldrich
Sucrose, BioXtra, ≥99.5% (GC)
Sigma-Aldrich
Sucrose, ≥99.5% (GC)
Sigma-Aldrich
HEPES buffer solution, 1 M in H2O
SAFC
HEPES
Sigma-Aldrich
Propidium iodide solution, solution (1.0 mg/ml in water)
Sigma-Aldrich
Sucrose, BioUltra, for molecular biology, ≥99.5% (HPLC)
Sigma-Aldrich
Sucrose, puriss., meets analytical specification of Ph. Eur., BP, NF
Sigma-Aldrich
Sucrose, ≥99.5%
Sigma-Aldrich
Temozolomide, ≥98% (HPLC)
Sigma-Aldrich
Trypan Blue, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Sucrose, ACS reagent
Sigma-Aldrich
Sucrose, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.5% (GC)
Sigma-Aldrich
HEPES, BioUltra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate hydrate, 98%
Sigma-Aldrich
Sucrose, meets USP testing specifications
Sigma-Aldrich
HEPES, BioXtra, pH 5.0-6.5 (1 M in H2O), ≥99.5% (titration)
Sigma-Aldrich
HEPES, BioXtra, suitable for mouse embryo cell culture, ≥99.5% (titration)
Sigma-Aldrich
Sucrose, Grade II, suitable for plant cell culture
Sigma-Aldrich
Trypan Blue, Dye content 60 %
Sigma-Aldrich
Salinomycin, from Streptomyces albus, ≥98% (HPLC)
Sigma-Aldrich
HEPES, anhydrous, free-flowing, Redi-Dri, ≥99.5%
Sigma-Aldrich
Sucrose, Grade I, suitable for plant cell culture
Sigma-Aldrich
DL-Cysteine, technical grade

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.