5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells.

5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Research Abstract Details 

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5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Abstract Text:

Surajit Karmakar,Naren L Banik,Sunil J Patel,Swapan K Ray,

Glioblastoma is the most common astrocytic brain tumor in humans. Current therapies for this malignancy are mostly ineffective. Photodynamic therapy (PDT), an exciting treatment strategy based on activation of a photosensitizer, has not yet been extensively explored for treating glioblastoma. We used 5-aminolevulinic acid (5-ALA) as a photosensitizer for PDT to induce apoptosis in human malignant glioblastoma U87MG cells and to understand the underlying molecular mechanisms. Trypan blue dye exclusion test showed a decrease in cell viability after exposure to increasing doses of 5-ALA for 4h followed by PDT with a broad spectrum blue light (400-550 nm) at a dose of 18J/cm(2) for 1h and then incubation at 37 degrees C for 4h. Following 0.5 and 1mM 5-ALA-based PDT (5-ALA-PDT), Wright staining and ApopTag assay showed occurrence of apoptosis morphologically and biochemically, respectively. After 5-ALA-PDT, down regulation of nuclear factor kappa B (NFkappaB) and baculovirus inhibitor-of-apoptosis repeat containing-3 (BIRC-3) protein indicated inhibition of survival signals. Besides, 5-ALA-PDT caused increase in Bax:Bcl-2 ratio and mitochondrial release of cytochrome c and apoptosis-inducing factor (AIF). Activation of calpain, caspase-9, and caspase-3 occurred in course of apoptosis. Calpain and caspase-3 activities cleaved alpha-spectrin at specific sites generating 145kD spectrin breakdown product (SBDP) and 120kD SBDP, respectively. The results suggested that 5-ALA-PDT induced apoptosis in U87MG cells by suppression of survival signals and activation of proteolytic pathways. Thus, 5-ALA-PDT can be an effective strategy for inducing apoptosis in glioblastoma.

5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Publishing Authors By Initials

S Karmakar,NL Banik,SJ Patel,SK Ray,

For similar therapeutics: combined modality therapy: photochemotherapy research abstracts see: therapeutics: combined modality therapy: photochemotherapy research

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5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Neuroscience letters

VOLUME: 415

Page Numbers: 242-7

Journal Abbreviation: Neurosci. Lett.

ISSN: 0304-3940

DAY: 11

MONTH: 02

YEAR: 2007

5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Information

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LANGUAGE: eng

NlmUniqueID: 7600130

5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Keywords Mesh Terms:

KEYWORDS: Photochemotherapy

MESH TERMS: methods

Chemical & Substance for Abstract: 5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Information

Substance Name: Caspases

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for 5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells.

AFFILIATION: Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 323K, Charleston, SC 29425, USA.

Country: Ireland

AGENCY: United States NINDS

GRANT: R01 NS057811-01A1

ACRONYM: NS

MEDLINETA: Neurosci Lett

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