Different apoptotic pathways activated by oxaliplatin in primary astrocytes vs. colo-rectal cancer cells

International Journal of Molecular Sciences
M ZanardelliL Di Cesare Mannelli

Abstract

Oxaliplatin-based chemotherapy improves the outcomes of metastatic colorectal cancer patients. Its most significant and dose-limiting side effect is the development of a neuropathic syndrome. The mechanism of the neurotoxicity is unclear. The limited knowledge about differences existing between neurotoxic and antitumor effects hinders the discovery of effective and safe adjuvant therapies. In vitro, we suggested cell-specific activation apoptotic pathways in normal nervous cells (astrocytes) vs. colon-cancer cells (HT-29). In the present research we compared the apoptotic signals evoked by oxaliplatin in astrocytes and HT-29 analyzing the intrinsic and extrinsic apoptotic pathways. In astrocytes, oxaliplatin induced a mitochondrial derangement measured as cytosolic release of cytochrome C, increase in superoxide anion levels and decreased expression of the antiapoptotic protein Bcl-2. Caspase-8, a main initiator of the extrinsic process remained unaltered. On the contrary, in HT-29 oxaliplatin increased caspase-8 activity and Bid expression, thus activating the extrinsic apoptosis, while the Bcl-2 increased expression blocked the mitochondrial damage. Data suggest the preferred activation of the intrinsic apoptosis as oxaliplat...Continue Reading

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Citations

Feb 2, 2016·Free Radical Biology & Medicine·Lorenzo Di Cesare MannelliPaola Failli
Feb 6, 2017·Zeitschrift Für Naturforschung. C, a Journal of Biosciences·Lorenzo CinciCarla Ghelardini
Jun 9, 2016·Basic & Clinical Pharmacology & Toxicology·Enrica BianchiCarla Ghelardini
Aug 8, 2018·Frontiers in Physiology·Ana S PiresMaria F Botelho

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

Origin
ImageJ
OriginLab

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