Antioxidants, Oxidative Damage and Oxygen Deprivation Stress: a Review

Liposomal drug delivery systems: from concept to clinical applications.

http://europepmc.org/articles/PMC4146684?pdf=render

Cisplatin in cancer therapy: molecular mechanisms of action

Cisplatin, carboplatin and oxaliplatin are platinum-based drugs that are widely used in cancer chemotherapy. Platinum–DNA adducts, which are formed following uptake of the drug into the nucleus of cells, activate several cellular processes that mediate the cytotoxicity of these platinum drugs. This review focuses on recently discovered cellular pathways that are activated in response to cisplatin, including those involved in regulating drug uptake, the signalling of DNA damage, cell-cycle checkpoints and arrest, DNA repair and cell death. Such knowledge of the cellular processing of cisplatin adducts with DNA provides valuable clues for the rational design of more efficient platinum-based drugs as well as the development of new therapeutic strategies.

Cellular processing of platinum anticancer drugs.

A wide variety of pathogenic microorganisms have been demonstrated to cause eukaryotic cell death, either as a consequence of infecting host cells or by producing toxic products. Pathogen-induced host cell death has been characterized as apoptosis in many of these systems. It is increasingly being

Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells

The chemotherapeutic cisplatin causes renal dysfunction and renal proximal tubular cell (RPTC) apoptosis. The goal of these studies was to examine the role of p53, caspase 3, 8, and 9, and mitochondria in the signaling of cisplatin-induced apoptosis. Cisplatin (50 microM) produced time-dependent apoptosis in RPTCs, causing cell shrinkage, a 50-fold increase in caspase 3 activity, a 4-fold increase in phosphatidylserine externalization, and 5- and 15-fold increases in chromatin condensation and DNA hypoploidy, respectively. Mitochondrial membrane potential and ATP levels did not change at any time during cisplatin exposure. Caspase 8 and 9 activities also did not increase during treatment. Cisplatin increased nuclear p53 expression 4 h after treatment, preceding both caspase 3 activation and chromatin condensation. Treatment with the p53 inhibitor alpha-2-(2-imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone (PFT) before cisplatin exposure inhibited p53 nuclear expression at 4, 8, and 12 h and inhibited phosphatidylserine externalization and caspase 3 activation at 12 h. Neither DEVD-fmk nor ZVAD-fmk inhibited cisplatin-induced p53 nuclear expression. Both DEVD-fmk and ZVAD-fmk completely inhibited caspase 3 activity but, like PFT, partially inhibited cisplatin-induced chromatin condensation, annexin V labeling, and DNA hypoploidy after 24 h. These data demonstrate that at least 50% of cisplatin-induced apoptosis in RPTC is mediated by p53 and that p53 activates caspase 3 independently of either caspase 9 or 8 or mitochondrial dysfunction. Furthermore, 50% of cisplatin-induced RPTC apoptosis is independent of p53 and caspases 3, 8, and 9.

Cisplatin-induced renal cell apoptosis: caspase 3-dependent and -independent pathways.

Phospholipase A(2)s (PLA(2)s) represent a family of esterases that hydrolyze the sn-2 ester bond in phospholipids, releasing free fatty acids and lysophospholipids. PLA(2)s are important in the signaling of several cellular processes and are known to play a significant role in inflammation. Studies also show that PLA(2)s are modulators of drug-, chemical-, and ischemia/reperfusion-induced cellular injury. The role of PLA(2)s in apoptosis and oncosis depends upon the PLA(2) isoform, the cell type, and the stimulus of injury. The purpose of this review is to discuss the functions of iPLA(2), cPLA(2) and sPLA(2) isoforms in oncosis and apoptosis, including oxidant-induced and receptor-mediated cell death. In addition, the measurement and modulation of PLA(2) is discussed.

Phospholipase A 2 s in Cell Injury and Death

Phospholipids are important constituents of all living cell membranes Lipidomics is a rapidly growing field that provides insight as to how specific phospholipids play roles in normal physiological and disease states There are many analytical methods available for the qualitative and quantitative determination of phospholipids This review provides a summary of the methods that were historically used such as thin layer chromatography, gas chromatography and high-performance liquid chromatography In addition, an introduction to applications of interfacing these traditional chromatographic techniques with mass spectrometry is provided

https://onlinelibrary.wiley.com/doi/pdf/10.1002/bmc.563

A review of chromatographic methods for the assessment of phospholipids in biological samples

Methods for assessing mammalian cell death are presented in this unit. The unit is divided into six sections: (1) a brief overview of cytotoxicity and pathways of cell death, (2) a method to measure cell death using lactate dehydrogenase (LDH) release as a marker of membrane integrity, (3) a flow cytometry method that simultaneously measures two types of cell death, necrosis, and apoptosis, (4) use of fluorescence microscopy and nuclear morphology to assess apoptosis and necrosis, (5) the use of multi-well plates and high-content analysis imaging systems to assess nuclear morphology, and (6) a discussion of the use of cytotoxicity assays to determine the mechanisms of cell death.

/pdf/measurement-of-cell-death-in-mammalian-cells-1s8dr9povi.pdf

Brian S. Cummings

Papers

Cisplatin-induced renal cell apoptosis: caspase 3-dependent and -independent pathways.

Phospholipase A 2 s in Cell Injury and Death

A review of chromatographic methods for the assessment of phospholipids in biological samples

Measurement of Cell Death in Mammalian Cells

Phospholipase A2 as targets for anti-cancer drugs.