Sonodynamic and photodynamic mechanisms of action of the novel hypocrellin sonosensitizer, SL017: mitochondrial cell death is attenuated by 11, 12-epoxyeicosatrienoic acid

Summary Development of sonosensitizers for sonodynamic therapy (SDT) which selectively target abnormal cells can limit undesired side effects in chemotherapeutic applications. Hypocrellin-B (HB) derivatives are low molecular weight compounds which belong to the perylenequinone family of photosensiti...

Full description

Saved in:
Bibliographic Details
Published in:Investigational new drugs 2011-12, Vol.29 (6), p.1328-1336
Main Authors: El-Sikhry, Haitham E., Miller, Gerald G., Madiyalakan, Madi R., Seubert, John M.
Format: Article
Language:English
Subjects:
8,11,14-Eicosatrienoic Acid - analogs & derivatives
8,11,14-Eicosatrienoic Acid - pharmacology
Apoptosis
Cancer therapies
Cell death
Cell Death - drug effects
Cells, Cultured
Cytochrome
Cytotoxicity
Dose-Response Relationship, Drug
Drugs
Energy
Fibroblasts - drug effects
Fibroblasts - metabolism
Humans
Investigations
Light
Localization
Medicine
Medicine & Public Health
Membrane Potential, Mitochondrial - drug effects
Mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
Molecular weight
Morphology
Oncology
Perylene - administration & dosage
Perylene - analogs & derivatives
Perylene - pharmacology
Pharmacology
Pharmacology/Toxicology
Pharmacy
Photochemotherapy - methods
Photodynamic therapy
Photosensitizing Agents - administration & dosage
Photosensitizing Agents - pharmacology
Preclinical Studies
Quinones - administration & dosage
Quinones - pharmacology
Reactive Oxygen Species - metabolism
Studies
Ultrasonic imaging
Ultrasonic Therapy - methods
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Development of sonosensitizers for sonodynamic therapy (SDT) which selectively target abnormal cells can limit undesired side effects in chemotherapeutic applications. Hypocrellin-B (HB) derivatives are low molecular weight compounds which belong to the perylenequinone family of photosensitizing and sonosensitizing compounds. In this study, we investigate the cytotoxic mechanisms of a novel HB-derived photo- and sonosensitizer, SL017. Human fibroblast WI-38 cells were treated with SL017 (0 μM, 0.1 μM or 10 μM) and subjected to photodynamic therapy (PDT) or SDT. Studies demonstrate that maximal uptake of SL017 occurs within 30 min, with a mitochondrial subcellular localization. Activation of SL017 by either visible light or ultrasound resulted in significant increases in reactive oxygen species (ROS) production as measured by CM-H2-DCFDA (5-(and-6)-chloromethyl-2′7′-dichlorodihydrofluorescein diacetate acetyl ester). Co-administration of the antioxidant, ascorbic acid, attenuated ROS production. Low concentrations of SL017 (100 nM) induced a rapid (
ISSN:0167-6997
1573-0646
DOI:10.1007/s10637-010-9495-2