scholarly journals Cationic Amphiphilic Drugs Cause a Marked Expansion of Apparent Lysosomal Volume: Implications for an Intracellular Distribution-Based Drug Interaction

2012 ◽  
Vol 9 (5) ◽  
pp. 1384-1395 ◽  
Author(s):  
Ryan S. Funk ◽  
Jeffrey P. Krise
Keyword(s):  
Drug Interaction ◽  
Intracellular Distribution ◽  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs

scholarly journals Erratum: Corrigendum: New insights into the intracellular distribution pattern of cationic amphiphilic drugs

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Magdalena Vater ◽  
Leonhard Möckl ◽  
Vanessa Gormanns ◽  
Carsten Schultz Fademrecht ◽  
Anna M. Mallmann ◽  
...  
Keyword(s):  
Distribution Pattern ◽  
Intracellular Distribution ◽  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs

scholarly journals New insights into the intracellular distribution pattern of cationic amphiphilic drugs

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Magdalena Vater ◽  
Leonhard Möckl ◽  
Vanessa Gormanns ◽  
Carsten Schultz Fademrecht ◽  
Anna M. Mallmann ◽  
...  
Keyword(s):  
Distribution Pattern ◽  
Morphological Changes ◽  
Intracellular Distribution ◽  
Intact Cells ◽  
Lysosomal Compartment ◽  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs ◽  
Intracellular Compartments ◽  
High Concentrations ◽  
First Time

Abstract Cationic amphiphilic drugs (CADs) comprise a wide variety of different substance classes such as antidepressants, antipsychotics, and antiarrhythmics. It is well recognized that CADs accumulate in certain intracellular compartments leading to specific morphological changes of cells. So far, no adequate technique exists allowing for ultrastructural analysis of CAD in intact cells. Azidobupramine, a recently described multifunctional antidepressant analogue, allows for the first time to perform high-resolution studies of CADs on distribution pattern and morphological changes in intact cells. We showed here that the intracellular distribution pattern of azidobupramine strongly depends on drug concentration and exposure time. The mitochondrial compartment (mDsRed) and the late endo-lysosomal compartment (CD63-GFP) were the preferred localization sites at low to intermediate concentrations (i.e. 1 μM, 5 μM). In contrast, the autophagosomal compartment (LC3-GFP) can only be reached at high concentrations (10 μM) and long exposure times (72 hrs). At the morphological level, LC3-clustering became only prominent at high concentrations (10 μM), while changes in CD63 pattern already occurred at intermediate concentrations (5 μM). To our knowledge, this is the first study that establishes a link between intracellular CAD distribution pattern and morphological changes. Therewith, our results allow for gaining deeper understanding of intracellular effects of CADs.

Targeting Cancer Lysosomes with Good Old Cationic Amphiphilic Drugs

2020 ◽  
Author(s):  
Anne-Marie Ellegaard ◽  
Peter Bach ◽  
Marja Jäättelä
Keyword(s):  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs

scholarly journals Pathological Features of Corneal Phospholipidosis in Juvenile White Rabbits Induced by Ocular Instillation of Chloroquine or Amiodarone

2018 ◽  
Vol 47 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Yoshinori Yamagiwa ◽  
Yoshihiro Takei ◽  
Haruko Koizumi ◽  
Shingo Nemoto ◽  
Masaaki Kurata ◽  
...  
Keyword(s):  
Young Adults ◽  
Young Adult ◽  
Corneal Epithelium ◽  
Inclusion Bodies ◽  
Corneal Endothelium ◽  
Age Groups ◽  
Lamellar Bodies ◽  
Ultrastructural Examination ◽  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs

Cationic amphiphilic drugs (CADs) can induce phospholipidosis (PLD) in organs/tissues. Several ophthalmic pharmaceuticals containing CADs are marketed and used in children. To investigate the effect of PLD on the developing cornea, chloroquine and amiodarone, which are representative CADs, were applied topically to the eyes of juvenile rabbits, and the effects in juvenile rabbits were compared with those in young adult rabbits. Diffuse corneal cloudiness was observed in chloroquine- and amiodarone-treated eyes. Histopathologically, vacuolation was observed in the corneal epithelium and keratocytes. On ultrastructural examination, these vacuoles contained multilamellar inclusion bodies, which are a characteristic of PLD. The size of the vacuoles in the corneal epithelium was reduced in juveniles compared with young adults. Cytoplasmic lamellar bodies and exocytosis in the corneal endothelium were observed in young adult rabbits but not in juvenile rabbits. This study revealed that topical application of chloroquine or amiodarone induces corneal PLD in juvenile and young adult rabbits. Corneal endothelial changes occurred only in young adult rabbits, but ophthalmological changes were similar between juveniles and young adults. The results of the study suggest that the effects of corneal PLD were similar among age groups based on risk assessment.

scholarly journals Repurposing Cationic Amphiphilic Drugs and Derivatives to Engage Lysosomal Cell Death in Cancer Treatment

2020 ◽  
Vol 10 ◽  
Author(s):  
Michelle Hu ◽  
Kermit L. Carraway
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Cellular Transformation ◽  
Therapeutic Window ◽  
Cell Populations ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Membrane Rupture ◽  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs

A major confounding issue in the successful treatment of cancer is the existence of tumor cell populations that resist therapeutic agents and regimens. While tremendous effort has gone into understanding the biochemical mechanisms underlying resistance to each traditional and targeted therapeutic, a broader approach to the problem may emerge from the recognition that existing anti-cancer agents elicit their cytotoxic effects almost exclusively through apoptosis. Considering the myriad mechanisms cancer cells employ to subvert apoptotic death, an attractive alternative approach would leverage programmed necrotic mechanisms to side-step therapeutic resistance to apoptosis-inducing agents. Lysosomal cell death (LCD) is a programmed necrotic cell death mechanism that is engaged upon the compromise of the limiting membrane of the lysosome, a process called lysosomal membrane permeabilization (LMP). The release of lysosomal components into the cytosol upon LMP triggers biochemical cascades that lead to plasma membrane rupture and necrotic cell death. Interestingly, the process of cellular transformation appears to render the limiting lysosomal membranes of tumor cells more fragile than non-transformed cells, offering a potential therapeutic window for drug development. Here we outline the concepts of LMP and LCD, and discuss strategies for the development of agents to engage these processes. Importantly, the potential exists for existing cationic amphiphilic drugs such as antidepressants, antibiotics, antiarrhythmics, and diuretics to be repurposed to engage LCD within therapy-resistant tumor cell populations.

Induction of Apoptosis by Cationic Amphiphilic Drugs Amiodarone and Imipramine

2005 ◽  
Vol 28 (1) ◽  
pp. 117-133 ◽  
Author(s):  
Joseph R. Piccotti ◽  
Mark S. LaGattuta ◽  
Stephanie A. Knight ◽  
Andrea J. Gonzales ◽  
Michael R. Bleavins
Keyword(s):  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs ◽  
Induction Of Apoptosis
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