Invention of a novel photodynamic therapy for tumors using a photosensitizing PI3K inhibitor.

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27854
Title
Invention of a novel photodynamic therapy for tumors using a photosensitizing PI3K inhibitor.
File
Description

Abstract

XL147 (SAR245408, pilaralisib), an ATP-competitive pan-class I phosphoinositide 3-kinase (PI3K) inhibitor, is a promising new anticancer drug. We examined the effect of the PI3K inhibitor on PC3 prostate cancer cells under a fluorescence microscope and found that XL147-treated cancer cells are rapidly injured by blue wavelength (430 nm) light irradiation. During the irradiation, the cancer cells treated with 0.2-2 μM XL147 showed cell surface blebbing and cytoplasmic vacuolation and died within 15 min. The extent of cell injury/death was dependent on the dose of XL147 and the light power of the irradiation. These findings suggest that XL147 might act as a photosensitizing reagent in photodynamic therapy (PDT) for cancer. Moreover, the cytotoxic effect of photosensitized XL147 was reduced by pretreatment with other ATP-competitive PI3K inhibitors such as LY294002, suggesting that the cytotoxic effect of photosensitized XL147 is facilitated by binding to PI3K in cells. In a single-cell illumination analysis using a fluorescent probe to identify reactive oxygen species (ROS), significantly increased ROS production was observed in the XL147-treated cells when the cell was illuminated with blue light. Taken together, it is conceivable that XL147, which is preferentially accumulated in cancer cells, could be photosensitized by blue light to produce ROS to kill cancer cells. This study will open up new possibilities for PDT using anticancer drugs.

KEYWORDS:

PC3 prostatic cancer cells; PI3K inhibitors; XL147; live-cell imaging; photodynamic therapy; photosensitizer

(医博甲642)

Author
著者 林田 有史 
著者(ヨミ) ハヤシダ ユウシ
著者(別表記) Hayashida Yushi
Publication Title
International Journal of Cancer
Publication Title Alternative
Int J Cancer.
Volume
139
Issue
3
Start Page
700
End Page
711
Publisher
International Union against Cancer
Wiley
Published Date
2016-08-01
ISSN
0020-7136
NCID
AA00680002
PMID
26989815
DOI
10.1002/ijc.30097
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.1002/ijc.30097
Relation(isVersionOf)
Publisher's Version.
Text Version
ETD
Grant ID
博甲第642号
Grant Date
2016-06-28
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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